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Geoffrey Shapiro, MD, PhD


Medical Oncology

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Physician

  • Senior Vice President, Developmental Therapeutics
  • Clinical Director, Center for DNA Damage and Repair
  • Institute Physician
  • Professor of Medicine, Harvard Medical School

Clinical Interests

  • Developmental therapeutics
  • Phase 1 clinical trials
  • Solid tumors

Contact Information

  • Appointments617-632-3832
  • Office Phone Number617-632-3832
  • Fax617-632-2682

Bio

Dr. Shapiro received his PhD in 1987 and his MD in 1988 from Cornell University, followed by postgraduate training in internal medicine at Beth Israel Hospital, Boston, where he served as chief medical resident. He completed a fellowship in medical oncology at Dana-Farber Cancer Institute, during which he investigated the role of cell-cycle-related proteins in lung cancer. He joined the Dana-Farber faculty in 1994.



Dr. Shapiro's practice is focused in the Center for Cancer Therapeutic Innovation, where he develops and leads early phase clinical trials and provides mentoring to early career investigators. As Senior Vice President, Developmental Therapeutics, he also works integrally with multiple disease groups within the Institute

Board Certification:

  • Medical Oncology

Fellowship:

  • Dana-Farber Cancer Institute, Medical Oncology

Residency:

  • Beth Israel Hospital, Chief Medical Resident
  • Beth Israel Hospital, Internal Medicine

Medical School:

  • Weill Medical College of Cornell University

Research

Cell-Cycle-Related Targets for Antitumor Drug Development

Cyclin-dependent kinases (cdks) are critical regulators of cell cycle progression and RNA transcription. A variety of genetic and epigenetic events cause universal overactivity of the cdks in human cancer, and their inhibition frequently leads to cell cycle arrest, depletion of transcripts with short half-lives, and apoptosis. Using siRNA technology, we have recently shown that depletion of both cell cycle and transcriptional cdk activities induces apoptosis in transformed cells. A primary focus of our laboratory is the characterization of cdk inhibitor drugs that mimic these effects. We are investigating both pan-cdk inhibitors, including flavopiridol, as well as inhibitors more selective for cdks 1 and 2. These compounds induce p53-independent apoptosis in transformed cells and modulate phosphorylation of Rb, p27(Kip1) and E2F-1. We are designing pharmacodynamic assays to assess their biologic effects in tumors as early-phase trials begin. In addition, we have found that cdk inhibition is synergistic with DNA damage in inducing cancer cell death. Cdk inhibition following cell-cycle disruption by chemotherapy drugs may alter the activity of the transcription factor E2F-1, thereby activating apoptosis pathways. Clinical trials exploiting this biology are under way, including a combination of gemcitabine and flavopiridol. We have also investigated the geldanamaycins, small-molecule inhibitors of hsp90, a cellular chaperone required for the proper folding of multiple kinases, including cdk4. We have demonstrated the depletion of cdk4 in lung cancer cell lines treated with geldanamycins, an effect that induces retinoblastoma-dependent G1 arrest. During the course of this work, we discovered that lung cancer cell lines harboring kinase domain mutations of epidermal growth factor receptor (EGFR) were the most sensitive to hsp90 inhibition, and we have defined mutant EGFR as a novel hsp90 client protein that is rapidly depleted following geldanamycin treatment. Hsp90 inhibition may represent a promising strategy for EGFR mutant lung cancers that have acquired resistance to standard tyrosine kinase inhibitors.Another active area of investigation is in regulation of Aurora kinases, mitotic kinases that are frequently dysregulated in cancer. We have shown that the Aurora kinase inhibitor VX-680 induces endoreduplication and eventual cell death in cancer cells. This effect is markedly enhanced in cells with a compromised p53-p21-dependent post-mitotic checkpoint. Transformed cells lacking the post-mitotic checkpoint are most likely to die in response to VX-680, while cells with intact checkpoint function are more likely to arrest. This work represents a first step toward defining tumors that are more likely to respond to Aurora kinase inhibition.

Phase 1 study of the ATR inhibitor berzosertib in combination with cisplatin in patients with advanced solid tumours. Br J Cancer. 2021 May 26.
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FGFR2 Extracellular Domain In-Frame Deletions are Therapeutically Targetable Genomic Alterations that Function as Oncogenic Drivers in Cholangiocarcinoma. Cancer Discov. 2021 Apr 29.
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EZH2 inhibition activates a dsRNA-STING-interferon stress axis that potentiates response to PD-1 checkpoint blockade in prostate cancer. Nat Cancer. 2021 Apr; 2(4):444-456.
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Immune modulating activity of the CHK1 inhibitor prexasertib and anti-PD-L1 antibody LY3300054 in patients with high-grade serous ovarian cancer and other solid tumors. Cancer Immunol Immunother. 2021 Mar 20.
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Phase II Clinical Trial of Everolimus in a Pan-Cancer Cohort of Patients with mTOR Pathway Alterations. Clin Cancer Res. 2021 Mar 16.
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MMB-FOXM1-driven premature mitosis is required for CHK1 inhibitor sensitivity. Cell Rep. 2021 Mar 02; 34(9):108808.
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Pharmacokinetics and Safety of PTC596, a Novel Tubulin-Binding Agent, in Subjects With Advanced Solid Tumors. Clin Pharmacol Drug Dev. 2021 Jan 13.
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Molecular Characterization and Therapeutic Targeting of Colorectal Cancers Harboring Receptor Tyrosine Kinase Fusions. Clin Cancer Res. 2021 Mar 15; 27(6):1695-1705.
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Targeting immunosuppressive macrophages overcomes PARP inhibitor resistance in BRCA1-associated triple-negative breast cancer. Nat Cancer. 2021 Jan; 2(1):66-82.
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A Phase 1 study of RO6870810, a novel bromodomain and extra-terminal protein inhibitor, in patients with NUT carcinoma, other solid tumours, or diffuse large B-cell lymphoma. Br J Cancer. 2021 02; 124(4):744-753.
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Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer. Clin Cancer Res. 2021 Feb 15; 27(4):983-991.
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CHK1 Inhibitor Blocks Phosphorylation of FAM122A and Promotes Replication Stress. Mol Cell. 2020 11 05; 80(3):410-422.e6.
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Phase 1 study of the HSP90 inhibitor onalespib in combination with AT7519, a pan-CDK inhibitor, in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2020 12; 86(6):815-827.
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KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med. 2020 09 24; 383(13):1207-1217.
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A phase Ib open-label dose escalation study of the safety, pharmacokinetics, and pharmacodynamics of cobimetinib (GDC-0973) and ipatasertib (GDC-0068) in patients with locally advanced or metastatic solid tumors. Invest New Drugs. 2021 Feb; 39(1):163-174.
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A Phase I Study of DLYE5953A, an Anti-LY6E Antibody Covalently Linked to Monomethyl Auristatin E, in Patients with Refractory Solid Tumors. Clin Cancer Res. 2020 11 01; 26(21):5588-5597.
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Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2020 07; 21(7):957-968.
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A Phase Ib Study to Evaluate the MEK Inhibitor Cobimetinib in Combination with the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors. Oncologist. 2020 10; 25(10):833-e1438.
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Biomarker-Guided Development of DNA Repair Inhibitors. Mol Cell. 2020 06 18; 78(6):1070-1085.
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Author Correction: Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer. Nat Commun. 2020 05 18; 11(1):2543.
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Combined Targeting of the BRD4-NUT-p300 Axis in NUT Midline Carcinoma by Dual Selective Bromodomain Inhibitor, NEO2734. Mol Cancer Ther. 2020 07; 19(7):1406-1414.
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Impact of DNA Damage Response and Repair (DDR) Gene Mutations on Efficacy of PD-(L)1 Immune Checkpoint Inhibition in Non-Small Cell Lung Cancer. Clin Cancer Res. 2020 08 01; 26(15):4135-4142.
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Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer. Nat Commun. 2020 03 19; 11(1):1459.
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A phase 1 study evaluating safety and pharmacokinetics of losatuxizumab vedotin (ABBV-221), an anti-EGFR antibody-drug conjugate carrying monomethyl auristatin E, in patients with solid tumors likely to overexpress EGFR. Invest New Drugs. 2020 10; 38(5):1483-1494.
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Reversion and non-reversion mechanisms of resistance to PARP inhibitor or platinum chemotherapy in BRCA1/2-mutant metastatic breast cancer. Ann Oncol. 2020 05; 31(5):590-598.
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Cooperation of the ATM and Fanconi Anemia/BRCA Pathways in Double-Strand Break End Resection. Cell Rep. 2020 02 18; 30(7):2402-2415.e5.
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Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Ann Oncol. 2019 Jul; 30(7):1121-1126.
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Dose-escalation trial of the ALK, MET & ROS1 inhibitor, crizotinib, in patients with advanced cancer. Future Oncol. 2020 Jan; 16(1):4289-4301.
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An Anatomical Site and Genetic-Based Prognostic Model for Patients With Nuclear Protein in Testis (NUT) Midline Carcinoma: Analysis of 124 Patients. JNCI Cancer Spectr. 2020 Apr; 4(2):pkz094.
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A Phase I Study of LY3009120, a Pan-RAF Inhibitor, in Patients with Advanced or Metastatic Cancer. Mol Cancer Ther. 2020 02; 19(2):460-467.
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Functional profiling of nucleotide Excision repair in breast cancer. DNA Repair (Amst). 2019 10; 82:102697.
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The CHK1 Inhibitor Prexasertib Exhibits Monotherapy Activity in High-Grade Serous Ovarian Cancer Models and Sensitizes to PARP Inhibition. Clin Cancer Res. 2019 10 15; 25(20):6127-6140.
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Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Ann Oncol. 2019 07 01; 30(7):1121-1126.
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Phase Ib study of the MEK inhibitor cobimetinib (GDC-0973) in combination with the PI3K inhibitor pictilisib (GDC-0941) in patients with advanced solid tumors. Invest New Drugs. 2020 04; 38(2):419-432.
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PARP Inhibitor Efficacy Depends on CD8+ T-cell Recruitment via Intratumoral STING Pathway Activation in BRCA-Deficient Models of Triple-Negative Breast Cancer. Cancer Discov. 2019 06; 9(6):722-737.
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Crizotinib in advanced ROS1-rearranged non-small cell lung cancer (NSCLC): Overall survival (OS) and updated safety from PROFILE 1001. Ann Oncol. 2019 Apr; 30 Suppl 2:ii48-ii49.
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Olaparib and a-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial. Lancet Oncol. 2019 04; 20(4):570-580.
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MicroRNA-Mediated Suppression of the TGF-ß Pathway Confers Transmissible and Reversible CDK4/6 Inhibitor Resistance. Cell Rep. 2019 03 05; 26(10):2667-2680.e7.
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Targeting MYC dependency in ovarian cancer through inhibition of CDK7 and CDK12/13. Elife. 2018 11 13; 7.
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Prediction of DNA Repair Inhibitor Response in Short-Term Patient-Derived Ovarian Cancer Organoids. Cancer Discov. 2018 11; 8(11):1404-1421.
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Palbociclib resistance confers dependence on an FGFR-MAP kinase-mTOR-driven pathway in KRAS-mutant non-small cell lung cancer. Oncotarget. 2018 Aug 03; 9(60):31572-31589.
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Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine. Cancer Discov. 2018 09; 8(9):1096-1111.
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Pharmacokinetic Study of Rucaparib in Patients With Advanced Solid Tumors. Clin Pharmacol Drug Dev. 2019 01; 8(1):107-118.
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RAS-MAPK Reactivation Facilitates Acquired Resistance in FGFR1-Amplified Lung Cancer and Underlies a Rationale for Upfront FGFR-MEK Blockade. . 2018 07; 17(7):1526-1539.
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Cabozantinib in Patients with Advanced Merkel Cell Carcinoma. Oncologist. 2018 07; 23(7):814-821.
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First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study. Cancer Discov. 2018 02; 8(2):184-195.
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Genomic Biomarkers Predicting Response to Selective CDK4/6 Inhibition: Progress in an Elusive Search. Cancer Cell. 2017 12 11; 32(6):721-723.
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CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation. Cancer Discov. 2018 02; 8(2):216-233.
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Synergy of WEE1 and mTOR Inhibition in Mutant KRAS-Driven Lung Cancers. Clin Cancer Res. 2017 Nov 15; 23(22):6993-7005.
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Immunotherapy with single agent nivolumab for advanced leiomyosarcoma of the uterus: Results of a phase 2 study. Cancer. 2017 Sep 01; 123(17):3285-3290.
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The evolving role of cyclin-dependent kinase inhibitors in cancer management. Clin Adv Hematol Oncol. 2017 Mar; 15(3):174-177.
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A phase 1 study of the pharmacokinetics of nucleoside analog trifluridine and thymidine phosphorylase inhibitor tipiracil (components of TAS-102) vs trifluridine alone. Invest New Drugs. 2017 04; 35(2):189-197.
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First-in-human trial of an anti-5T4 antibody-monomethylauristatin conjugate, PF-06263507, in patients with advanced solid tumors. Invest New Drugs. 2017 06; 35(3):315-323.
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CDK12 Inhibition Reverses De Novo and Acquired PARP Inhibitor Resistance in BRCA Wild-Type and Mutated Models of Triple-Negative Breast Cancer. Cell Rep. 2016 11 22; 17(9):2367-2381.
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Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study. J Clin Oncol. 2017 Jan 10; 35(2):157-165.
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Institutional implementation of clinical tumor profiling on an unselected cancer population. JCI Insight. 2016 11 17; 1(19):e87062.
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A phase 1 study combining the HER3 antibody seribantumab (MM-121) and cetuximab with and without irinotecan. Invest New Drugs. 2017 02; 35(1):68-78.
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Phase I Study Evaluating WEE1 Inhibitor AZD1775 As Monotherapy and in Combination With Gemcitabine, Cisplatin, or Carboplatin in Patients With Advanced Solid Tumors. J Clin Oncol. 2016 12 20; 34(36):4371-4380.
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Cabozantinib for metastatic breast carcinoma: results of a phase II placebo-controlled randomized discontinuation study. Breast Cancer Res Treat. 2016 11; 160(2):305-312.
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Clinical Development of the CDK4/6 Inhibitors Ribociclib and Abemaciclib in Breast Cancer. Breast Care (Basel). 2016 Jun; 11(3):167-73.
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Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid Tumors. Cancer Discov. 2016 07; 6(7):740-53.
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The BRCA1-?11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin. Cancer Res. 2016 05 01; 76(9):2778-90.
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Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor Veliparib (ABT-888) in Combination with Irinotecan in Patients with Advanced Solid Tumors. Clin Cancer Res. 2016 07 01; 22(13):3227-37.
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ASP9853, an inhibitor of inducible nitric oxide synthase dimerization, in combination with docetaxel: preclinical investigation and a Phase I study in advanced solid tumors. Cancer Chemother Pharmacol. 2016 Mar; 77(3):549-58.
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Incorporation of Next-Generation Sequencing into Routine Clinical Care to Direct Treatment of Head and Neck Squamous Cell Carcinoma. Clin Cancer Res. 2016 06 15; 22(12):2939-49.
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Targeting CDK4 and CDK6: From Discovery to Therapy. Cancer Discov. 2016 Apr; 6(4):353-67.
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Erratum to: A Phase 1 dose-escalation study of the safety and pharmacokinetics of once-daily oral foretinib, a multi-kinase inhibitor, in patients with solid tumors. Invest New Drugs. 2015 Dec; 33(6):1292.
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Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer. Cancer Discov. 2015 Nov; 5(11):1137-54.
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Phase I Study of the Investigational NEDD8-Activating Enzyme Inhibitor Pevonedistat (TAK-924/MLN4924) in Patients with Advanced Solid Tumors. Clin Cancer Res. 2016 Feb 15; 22(4):847-57.
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A phase I study of VS-6063, a second-generation focal adhesion kinase inhibitor, in patients with advanced solid tumors. Invest New Drugs. 2015 10; 33(5):1100-7.
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Intratumoral Heterogeneity in EGFR-Mutant NSCLC Results in Divergent Resistance Mechanisms in Response to EGFR Tyrosine Kinase Inhibition. Cancer Res. 2015 Oct 15; 75(20):4372-83.
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Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor. N Engl J Med. 2015 Jul 30; 373(5):428-37.
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Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer. Invest New Drugs. 2015 Oct; 33(5):1108-14.
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A phase 1 study of ABT-806 in subjects with advanced solid tumors. Invest New Drugs. 2015 Jun; 33(3):671-8.
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First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer. Clin Cancer Res. 2015 04 15; 21(8):1888-95.
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Cutaneous keratoacanthomas/squamous cell carcinomas associated with neutralization of transforming growth factor ß by the monoclonal antibody fresolimumab (GC1008). Cancer Immunol Immunother. 2015 Apr; 64(4):437-46.
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DNA-PK-A candidate driver of hepatocarcinogenesis and tissue biomarker that predicts response to treatment and survival. Clin Cancer Res. 2015 Feb 15; 21(4):925-33.
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The biology and clinical development of MEK inhibitors for cancer. Drugs. 2014 Dec; 74(18):2111-28.
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First-in-human phase I dose escalation study of a second-generation non-ansamycin HSP90 inhibitor, AT13387, in patients with advanced solid tumors. Clin Cancer Res. 2015 Jan 01; 21(1):87-97.
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Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Nov 20; 371(21):1963-71.
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A Phase I, dose-finding study in patients with advanced solid malignancies of the oral ?-secretase inhibitor PF-03084014. Clin Cancer Res. 2015 Jan 01; 21(1):60-7.
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Evaluation of statistical designs in phase I expansion cohorts: the Dana-Farber/Harvard Cancer Center experience. J Natl Cancer Inst. 2014 Jul; 106(7).
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A phase I clinical trial of navitoclax, a targeted high-affinity Bcl-2 family inhibitor, in combination with gemcitabine in patients with solid tumors. Invest New Drugs. 2014 Oct; 32(5):937-45.
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Activating mTOR mutations in a patient with an extraordinary response on a phase I trial of everolimus and pazopanib. Cancer Discov. 2014 May; 4(5):546-53.
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Phase I study of GC1008 (fresolimumab): a human anti-transforming growth factor-beta (TGFß) monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma. PLoS One. 2014; 9(3):e90353.
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Crizotinib as salvage and maintenance with allogeneic stem cell transplantation for refractory anaplastic large cell lymphoma. J Natl Compr Canc Netw. 2014 Mar 01; 12(3):323-6; quiz 326.
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Phase I safety and pharmacokinetic study of the PI3K/mTOR inhibitor SAR245409 (XL765) in combination with erlotinib in patients with advanced solid tumors. J Thorac Oncol. 2014 Mar; 9(3):316-23.
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Co-clinical trials demonstrate superiority of crizotinib to chemotherapy in ALK-rearranged non-small cell lung cancer and predict strategies to overcome resistance. Clin Cancer Res. 2014 Mar 01; 20(5):1204-1211.
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Phase I study of neratinib in combination with temsirolimus in patients with human epidermal growth factor receptor 2-dependent and other solid tumors. J Clin Oncol. 2014 Jan 10; 32(2):68-75.
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A phase 1 open-label, sequential dose-escalation study investigating the safety, tolerability, and pharmacokinetics of intravenous TLC388 administered to patients with advanced solid tumors. Invest New Drugs. 2014 Jun; 32(3):445-51.
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Preclinical activity profile and therapeutic efficacy of the HSP90 inhibitor ganetespib in triple-negative breast cancer. Clin Cancer Res. 2014 Jan 15; 20(2):413-24.
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Phase I safety, pharmacokinetic, and pharmacodynamic study of SAR245408 (XL147), an oral pan-class I PI3K inhibitor, in patients with advanced solid tumors. Clin Cancer Res. 2014 Jan 01; 20(1):233-45.
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NUT midline carcinoma: an aggressive intrathoracic neoplasm. J Thorac Oncol. 2013 Oct; 8(10):1335-8.
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Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance. Proc Natl Acad Sci U S A. 2013 Oct 15; 110(42):17041-6.
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Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov. 2013 Dec; 3(12):1355-63.
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Aurora kinase inhibition as an anticancer strategy. J Clin Oncol. 2014 Jan 01; 32(1):57-9.
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Phase 2 trial of afatinib, an ErbB family blocker, in solid tumors genetically screened for target activation. Cancer. 2013 Aug 15; 119(16):3043-51.
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First-in-human phase I dose-escalation study of the HSP90 inhibitor AUY922 in patients with advanced solid tumors. Clin Cancer Res. 2013 Jul 01; 19(13):3671-80.
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Poly(ADP-ribose) polymerase inhibitors as cancer therapy. Front Biosci (Landmark Ed). 2013 Jun 01; 18:1392-406.
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A multicenter phase II study of ganetespib monotherapy in patients with genotypically defined advanced non-small cell lung cancer. Clin Cancer Res. 2013 Jun 01; 19(11):3068-77.
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A phase I trial of vorinostat and alvocidib in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2. Clin Cancer Res. 2013 Apr 01; 19(7):1873-83.
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Sunitinib in combination with gemcitabine for advanced solid tumours: a phase I dose-finding study. Br J Cancer. 2013 Apr 16; 108(7):1393-401.
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Phase I dose-escalation study of afatinib, an ErbB family blocker, plus docetaxel in patients with advanced cancer. Future Oncol. 2013 Feb; 9(2):271-81.
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First-in-humans trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liver involvement. Cancer Discov. 2013 Apr; 3(4):406-17.
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Effect of aprepitant on the pharmacokinetics of the cyclin-dependent kinase inhibitor dinaciclib in patients with advanced malignancies. Cancer Chemother Pharmacol. 2012 Dec; 70(6):891-8.
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A Phase 1 dose-escalation study of the safety and pharmacokinetics of once-daily oral foretinib, a multi-kinase inhibitor, in patients with solid tumors. Invest New Drugs. 2013 Jun; 31(3):742-50.
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Cyclin-dependent kinase 4/6 inhibition in cancer therapy. . 2012 Nov 01; 11(21):3913.
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Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012 Oct; 13(10):1011-9.
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Ganetespib (STA-9090), a nongeldanamycin HSP90 inhibitor, has potent antitumor activity in in vitro and in vivo models of non-small cell lung cancer. Clin Cancer Res. 2012 Sep 15; 18(18):4973-85.
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Phase II trial of the histone deacetylase inhibitor romidepsin in patients with recurrent/metastatic head and neck cancer. Oral Oncol. 2012 Dec; 48(12):1281-8.
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BCL2 suppresses PARP1 function and nonapoptotic cell death. Cancer Res. 2012 Aug 15; 72(16):4193-203.
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Phase I study of barasertib (AZD1152), a selective inhibitor of Aurora B kinase, in patients with advanced solid tumors. Invest New Drugs. 2013 Apr; 31(2):370-80.
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A phase I first-in-human trial of bardoxolone methyl in patients with advanced solid tumors and lymphomas. Clin Cancer Res. 2012 Jun 15; 18(12):3396-406.
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Suppression of heat shock protein 27 induces long-term dormancy in human breast cancer. Proc Natl Acad Sci U S A. 2012 May 29; 109(22):8699-704.
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Combined EGFR/MET or EGFR/HSP90 inhibition is effective in the treatment of lung cancers codriven by mutant EGFR containing T790M and MET. Cancer Res. 2012 Jul 01; 72(13):3302-11.
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Phase I study of RO4929097, a gamma secretase inhibitor of Notch signaling, in patients with refractory metastatic or locally advanced solid tumors. J Clin Oncol. 2012 Jul 01; 30(19):2348-53.
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Phase II study of single-agent navitoclax (ABT-263) and biomarker correlates in patients with relapsed small cell lung cancer. Clin Cancer Res. 2012 Jun 01; 18(11):3163-9.
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Personalized tumor response assessment in the era of molecular medicine: cancer-specific and therapy-specific response criteria to complement pitfalls of RECIST. AJR Am J Roentgenol. 2012 Apr; 198(4):737-45.
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Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma. Blood. 2012 May 17; 119(20):4597-607.
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Chemotherapy-induced p53-dependent and -independent DNA damage responses are enhanced by poly(ADP-ribose) polymerase (PARP) inhibition in BRCA-proficient cancer cells. . 2012 Feb 01; 11(3):432-3.
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The effect of food on the bioavailability of panobinostat, an orally active pan-histone deacetylase inhibitor, in patients with advanced cancer. Cancer Chemother Pharmacol. 2012 Feb; 69(2):555-62.
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Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011 Oct; 12(11):1004-12.
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Compromised CDK1 activity sensitizes BRCA-proficient cancers to PARP inhibition. Nat Med. 2011 Jun 26; 17(7):875-82.
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Lack of food effect on single-dose pharmacokinetics of brivanib, and safety and efficacy following multiple doses in subjects with advanced or metastatic solid tumors. Cancer Chemother Pharmacol. 2011 Dec; 68(6):1377-85.
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Dependence on the MUC1-C oncoprotein in non-small cell lung cancer cells. . 2011 May; 10(5):806-16.
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Phase II multicenter trial of voreloxin as second-line therapy in chemotherapy-sensitive or refractory small cell lung cancer. J Thorac Oncol. 2011 Feb; 6(2):384-6.
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Phase I study of Navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors. J Clin Oncol. 2011 Mar 01; 29(7):909-16.
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Phase I studies of CBP501, a G2 checkpoint abrogator, as monotherapy and in combination with cisplatin in patients with advanced solid tumors. Clin Cancer Res. 2011 May 15; 17(10):3431-42.
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Combination mTOR and IGF-1R inhibition: phase I trial of everolimus and figitumumab in patients with advanced sarcomas and other solid tumors. Clin Cancer Res. 2011 Feb 15; 17(4):871-9.
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Phase I safety, pharmacokinetic, and pharmacodynamic study of ENMD-2076, a novel angiogenic and Aurora kinase inhibitor, in patients with advanced solid tumors. Clin Cancer Res. 2011 Feb 15; 17(4):849-60.
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Crizotinib, a small-molecule dual inhibitor of the c-Met and ALK receptor tyrosine kinases. Curr Opin Investig Drugs. 2010 Dec; 11(12):1477-90.
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Cyclin-dependent kinases (cdks) and the DNA damage response: rationale for cdk inhibitor-chemotherapy combinations as an anticancer strategy for solid tumors. Expert Opin Ther Targets. 2010 Nov; 14(11):1199-212.
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The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers. Cancer Res. 2010 Dec 15; 70(24):10038-43.
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Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010 Oct 28; 363(18):1693-703.
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Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor. N Engl J Med. 2010 Oct 28; 363(18):1727-33.
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Inhibition of ALK, PI3K/MEK, and HSP90 in murine lung adenocarcinoma induced by EML4-ALK fusion oncogene. Cancer Res. 2010 Dec 01; 70(23):9827-36.
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Integrative genomic and proteomic analyses identify targets for Lkb1-deficient metastatic lung tumors. Cancer Cell. 2010 Jun 15; 17(6):547-59.
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Pattern of retinoblastoma pathway inactivation dictates response to CDK4/6 inhibition in GBM. Proc Natl Acad Sci U S A. 2010 Jun 22; 107(25):11501-6.
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A phase I open-label study evaluating the cardiovascular safety of sorafenib in patients with advanced cancer. Cancer Chemother Pharmacol. 2011 Apr; 67(4):751-64.
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A phase I study of foretinib, a multi-targeted inhibitor of c-Met and vascular endothelial growth factor receptor 2. Clin Cancer Res. 2010 Jul 01; 16(13):3507-16.
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Development of phosphoinositide-3 kinase pathway inhibitors for advanced cancer. Curr Oncol Rep. 2010 Mar; 12(2):87-94.
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Phase I study of the c-raf-1 antisense oligonucleotide ISIS 5132 in combination with carboplatin and paclitaxel in patients with previously untreated, advanced non-small cell lung cancer. J Thorac Oncol. 2009 Sep; 4(9):1156-62.
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Cdk1 participates in BRCA1-dependent S phase checkpoint control in response to DNA damage. Mol Cell. 2009 Aug 14; 35(3):327-39.
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A phase I dose escalation study of AUY922, a novel HSP90 inhibitor, in patients with advanced solid malignancies. J Clin Oncol. 2009 May 20; 27(15_suppl):3532.
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Clinical activity observed in a phase I dose escalation trial of an oral c-met and ALK inhibitor, PF-02341066. J Clin Oncol. 2009 May 20; 27(15_suppl):3509.
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A phase I and pharmacological study of MK-1775, a Wee1 tyrosine kinase inhibitor, in both monotherapy and in combination with gemcitabine, cisplatin, or carboplatin in patients with advanced solid tumors. J Clin Oncol. 2009 May 20; 27(15_suppl):3510.
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Influence of food on the pharmacokinetics (PK) of panobinostat (LBH589), an orally active histone deacetylase inhibitor, in patients with advanced cancer. J Clin Oncol. 2009 May 20; 27(15_suppl):2550.
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Predicting drug susceptibility of non-small cell lung cancers based on genetic lesions. J Clin Invest. 2009 Jun; 119(6):1727-40.
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A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors. Clin Cancer Res. 2009 Apr 01; 15(7):2552-8.
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HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy. Proc Natl Acad Sci U S A. 2009 Jan 13; 106(2):474-9.
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Early detection of erlotinib treatment response in NSCLC by 3'-deoxy-3'-[F]-fluoro-L-thymidine ([F]FLT) positron emission tomography (PET). PLoS One. 2008; 3(12):e3908.
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Hsp90 inhibition suppresses mutant EGFR-T790M signaling and overcomes kinase inhibitor resistance. Cancer Res. 2008 Jul 15; 68(14):5827-38.
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Heat shock protein 90 inhibition in lung cancer. J Thorac Oncol. 2008 Jun; 3(6 Suppl 2):S152-9.
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Summary statement novel agents in the treatment of lung cancer: Fifth Cambridge Conference assessing opportunities for combination therapy. J Thorac Oncol. 2008 Jun; 3(6 Suppl 2):S107-12.
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A phase I dose-escalation study of the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the novel cyclin-dependent kinase inhibitor SCH 727965 administered every 3 weeks in subjects with advanced malignancies. J Clin Oncol. 2008 May 20; 26(15_suppl):3532.
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Phase I studies of CBP501, a novel G2 checkpoint abrogator, alone and combined with cisplatin (CDDP) in advanced solid tumor patients (pts). J Clin Oncol. 2008 May 20; 26(15_suppl):2528.
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A phase I dose-finding study of sunitinib (SU) in combination with gemcitabine (G) in patients (pts) with advanced solid tumors. J Clin Oncol. 2008 May 20; 26(15_suppl):14522.
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Phase I trial with a novel oral NF-?B/STAT3 inhibitor RTA 402 in patients with solid tumors and lymphoid malignancies. J Clin Oncol. 2008 May 20; 26(15_suppl):3517.
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Phase I/II study of GC1008: A human anti-transforming growth factor-beta (TGFß) monoclonal antibody (MAb) in patients with advanced malignant melanoma (MM) or renal cell carcinoma (RCC). J Clin Oncol. 2008 May 20; 26(15_suppl):9028.
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Phase I study of flavopiridol in combination with Paclitaxel and Carboplatin in patients with non-small-cell lung cancer. Clin Lung Cancer. 2008 May; 9(3):160-5.
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BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models. Oncogene. 2008 Aug 07; 27(34):4702-11.
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PF00299804, an irreversible pan-ERBB inhibitor, is effective in lung cancer models with EGFR and ERBB2 mutations that are resistant to gefitinib. Cancer Res. 2007 Dec 15; 67(24):11924-32.
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Proapoptotic BH3-only BCL-2 family protein BIM connects death signaling from epidermal growth factor receptor inhibition to the mitochondrion. Cancer Res. 2007 Dec 15; 67(24):11867-75.
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Targeting aberrant PI3K pathway signaling with XL147, a potent, selective and orally bioavailable PI3K inhibitor [abstract]. Proc AACR-NCI-EORTC International Meeting on Molecular Targets and Cancer Therapeutics. 2007; A-C205.

Phase I dose-escalation study of the safety, pharmacokinetics (PK) and pharmacodynamics of XL880,a VEGFRR and MET kinase inhibitor, administered daily to patients with advanced malignancies [abstract]. Proc AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. 2007; A-B248.

Phase I trial with a novel orally administered synthetic triperpenoid RTA 402 (CDDO-Me) in patients with solid tumors and lymphoid malignancies [abstract]. Proc AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. 2007; A-B82.

LKB1 modulates lung cancer differentiation and metastasis. Nature. 2007 Aug 16; 448(7155):807-10.
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Bronchial and peripheral murine lung carcinomas induced by T790M-L858R mutant EGFR respond to HKI-272 and rapamycin combination therapy. Cancer Cell. 2007 Jul; 12(1):81-93.
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The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272. Oncogene. 2007 Jul 26; 26(34):5023-7.
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Allele-dependent variation in the relative cellular potency of distinct EGFR inhibitors. . 2007 May; 6(5):661-7.
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Clinical and translational studies of depsipeptide, a histone deacetylase inhibitor, in patients with squamous cell carcinoma of the head and neck: New York Cancer Consortium Trial P6335 [abstract]. Proc Am Soc Clin Oncol. 2007; 25:A6065.

Concomitant cdk1 and cdk2 depletion induces irreparable DNA damage, G2/M arrest and cell death [abstract]. Proc Am Assoc Cancer Res. 2007; 48:A4346.

Direct and indirect modulation of EGFR-mediated growth signaling by Hsp90 inhibition in NSCLCs resistant to EGFR tyrosine kinase inhibitors in vitro and in vivo [abstract]. Proc Am Assoc Cancer Res. 2007; 48:A5237.

Translational studies of depsipeptide, a histone deacetylase (HDAC) inhibitor in patients with head and neck cancer [abstract]. Proc Am Assoc Cancer Res. 2007; 48:A3524.

Phase I experience with c-met inhibitor XL880 administered orally to patients with solid tumors [abstract]. Proc Am Soc Clin Oncol. 2007; 25:A3526.

Entering a clinical trial: is it right for you?-a randomized study of the clinical trials video and its impact on the informed consent process [abstract]. Proc Am Soc Clin Oncol. 2007; 25:A9072.

Retinoblastoma family member deficiency increases endoreduplication and apoptosis in response to the pan-Aurora kinase inhibitor VE-465 [abstract]. Proc Am Assoc Cancer Res. 2007; 48:A5394.

Transcriptional profiling identifies cyclin D1 as a critical downstream effector of mutant epidermal growth factor receptor signaling. Cancer Res. 2006 Dec 01; 66(23):11389-98.
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Combined depletion of cell cycle and transcriptional cyclin-dependent kinase activities induces apoptosis in cancer cells. Cancer Res. 2006 Sep 15; 66(18):9270-80.
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The Aurora kinase inhibitor VX-680 induces endoreduplication and apoptosis preferentially in cells with compromised p53-dependent postmitotic checkpoint function. Cancer Res. 2006 Aug 01; 66(15):7668-77.
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Non-small-cell lung cancer and Ba/F3 transformed cells harboring the ERBB2 G776insV_G/C mutation are sensitive to the dual-specific epidermal growth factor receptor and ERBB2 inhibitor HKI-272. Cancer Res. 2006 Jul 01; 66(13):6487-91.
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A phase I clinical and pharmacokinetic (PK) trial of the aurora kinase (AK) inhibitor MK-0457 in cancer patients. J Clin Oncol. 2006 Jun 20; 24(18_suppl):3009.
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Pharmacokinetics of PT523, a novel aminopterin analogue, in patients with solid tumors. J Clin Oncol. 2006 Jun 20; 24(18_suppl):2052.
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The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies. Cancer Cell. 2006 Jun; 9(6):485-95.
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Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors. Proc Natl Acad Sci U S A. 2006 May 16; 103(20):7817-22.
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Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol. 2006 Apr 10; 24(11):1770-83.
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AZ703, an imidazo[1,2-a]pyridine inhibitor of cyclin-dependent kinases 1 and 2, induces E2F-1-dependent apoptosis enhanced by depletion of cyclin-dependent kinase 9. Cancer Res. 2006 Jan 01; 66(1):435-44.
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Multiple mechanisms of Mcl-1 depletion by the cyclin-dependent kinase inhibitor flavopiridol in mantle cell lymphoma cell lines [abstract]. Proc Am Assoc Cancer Res. 2006; 47:A2805.

Phase 1 trial of ARQ501, a novel checkpoint pathway activator, in patients with advanced solid tumors [abstract]. Proc Am Assoc Cancer Res. 2006; 47:LB-12.

CBP501, a novel cell cycle G2 checkpoint abrogator: preliminary results of the initial phase 1 and pharmacokinetic/pharmacodynamic study in patients with advanced solid tumors [abstract]. Eur J Cancer. 2006; 4:A346.

A phase 1 clinical and pharmacokinetic trial of the aurora kinase (AK) inhibitor MK-0457 in cancer patients [abstract]. Proc Am Soc Clin Oncol. 2006; 24:A3009.

A phase 1 dose escalation trial of ispinesib (SB-715992) administered days 1-3 of a 21-day cycle in patients with advanced solid tumors [abstract]. Proc Am Soc Clin Oncol. 2006; 24:A2026.

A phase 1 study of a novel spectrum-selective kinase inhibitor (SSKI) XL880, administered orally in pajtients with advanced tumors [abstract]. Proc Am Soc Clin Oncol. 2006; 24:A3041.

Pharmacokinetics of PT523, a novel aminopterin analogue in patients with solid tumors [abstract]. Proc Am Soc Clin Oncol. 2006; 24:A2052.

Pharmacodynamics of XL880 a novel spectrum-selective kinase inhibitor (SSKI) administered orally to patients with advanced solid tumors [abstract]. Eur J Cancer. 2006; 4:A404.

Epidermal growth factor receptors harboring kinase domain mutations associate with the heat shock protein 90 chaperone and are destabilized following exposure to geldanamycins. Cancer Res. 2005 Jul 15; 65(14):6401-8.
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Phase I trial of ARQ 501, an Activated Checkpoint Therapy (ACT) agent, in patients with advanced solid tumors. J Clin Oncol. 2005 Jun; 23(16_suppl):3042.
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Phase I trial of the matrix metalloproteinase inhibitor marimastat combined with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer. Clin Cancer Res. 2005 May 01; 11(9):3417-24.
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Flavopiridol reduces malignant transformation of the esophageal mucosa in p27 knockout mice. Oncogene. 2005 Mar 03; 24(10):1683-8.
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Pharmacodynamic assessment of the cyclin-dependent kinase inhibitor flaopiridol: Modulation of cdk targets in clinical samples [abstract]. Lab Invest. 2005; 18(Supplement):1375.

Phase 1 Trial of ARQ 501, an activated checkpoint therapy (trade mark ACT) agent, in patients with advanced solid tumors [abstract]. Proc Am Soc Clin Oncol. 2005; 23:A3042.

A phase 1 study of E7070, a chloroindolyl-sulfonamide, in combination with irinotecan in gastrointestinal and thoracic carcinomas [abstract]. Am Soc Clin Oncol Gastrointestinal Cancers Symposium. 2005; A290.

Pharmacodynamic assessment of the cyclin-dependent kinase inhibitor flavopiridol: Modualtion of cdk targets in clinical samples [abstract]. Modern Pathol. 2005; 18(Supplement):1375.

A phase I study of E7070, a chloroindolyl-sulfonamide, in combination with irinotecan in gastrointestinal and thoracic carcinomas [abstract]. Proc Am Soc Clin Oncol. 2005; 23:A2031.

A phase II clinical and pharmacodynamic study of E7070 in patients with metastatic, recurrent, or refractory squamous cell carcinoma of the head and neck: modulation of retinoblastoma protein phosphorylation by a novel chloroindolyl sulfonamide cell cycle inhibitor. Clin Cancer Res. 2004 Jul 15; 10(14):4680-7.
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Preclinical and clinical development of the cyclin-dependent kinase inhibitor flavopiridol. Clin Cancer Res. 2004 Jun 15; 10(12 Pt 2):4270s-4275s.
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Novel agents in the treatment of lung cancer: conference summary statement. Clin Cancer Res. 2004 Jun 15; 10(12 Pt 2):4199s-4204s.
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Bioluminescent imaging of Cdk2 inhibition in vivo. Nat Med. 2004 Jun; 10(6):643-8.
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The role of metastasis-associated protein 1 in prostate cancer progression. Cancer Res. 2004 Feb 01; 64(3):825-9.
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Flavopiridol-induced apoptosis during S phase requires E2F-1 and inhibition of cyclin A-dependent kinase activity. Cancer Res. 2003 Nov 01; 63(21):7410-22.
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Selective sensitization of transformed cells to flavopiridol-induced apoptosis following recruitment to S-phase. Cancer Res. 2002 Mar 15; 62(6):1707-17.
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Modulation of the c-Met/hepatocyte growth factor pathway in small cell lung cancer. Clin Cancer Res. 2002 Feb; 8(2):620-7.
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A phase II study of weekly paclitaxel in elderly patients with advanced non-small cell lung cancer. Clin Cancer Res. 2001 Dec; 7(12):3942-9.
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A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer. Clin Cancer Res. 2001 Jun; 7(6):1590-9.
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Small molecule inhibitors of cyclin-dependent kinases. M.V. Blagosklonny, editor. Cell Cycle Checkpoints and Cancer. 2001; 208-34.

The physiology of p16(INK4A)-mediated G1 proliferative arrest. Cell Biochem Biophys. 2000; 33(2):189-97.
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Anticancer drug targets: cell cycle and checkpoint control. J Clin Invest. 1999 Dec; 104(12):1645-53.
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Flavopiridol induces cell cycle arrest and p53-independent apoptosis in non-small cell lung cancer cell lines. Clin Cancer Res. 1999 Oct; 5(10):2925-38.
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Expression of the focal adhesion protein paxillin in lung cancer and its relation to cell motility. Oncogene. 1999 Jan 07; 18(1):67-77.
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p16INK4A participates in a G1 arrest checkpoint in response to DNA damage. Mol Cell Biol. 1998 Jan; 18(1):378-87.
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Mutation analysis of glial cell line-derived neurotrophic factor, a ligand for an RET/coreceptor complex, in multiple endocrine neoplasia type 2 and sporadic neuroendocrine tumors. J Clin Endocrinol Metab. 1997 Sep; 82(9):3025-8.
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p16INK4A as a human tumor suppressor. Biochim Biophys Acta. 1996 Mar 18; 1242(3):165-9.
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Multiple mechanisms of p16INK4A inactivation in non-small cell lung cancer cell lines. Cancer Res. 1995 Dec 15; 55(24):6200-9.
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A novel p16INK4A transcript. Cancer Res. 1995 Jul 15; 55(14):2995-7.
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Reciprocal Rb inactivation and p16INK4 expression in primary lung cancers and cell lines. Cancer Res. 1995 Feb 01; 55(3):505-9.
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Influenza virus gene expression: control mechanisms at early and late times of infection and nuclear-cytoplasmic transport of virus-specific RNAs. J Virol. 1987 Mar; 61(3):764-73.
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Transcription and replication of influenza virion RNA in the nucleus of infected cells. Cold Spring Harb Symp Quant Biol. 1987; 52:353-8.
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Inhibition of influenza viral mRNA synthesis in cells expressing the interferon-induced Mx gene product. J Virol. 1985 Oct; 56(1):201-6.
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