Profile
A personalized medicine cancer research study
Key leaders of the new genetic-screening research program include Dana-Farber’s Barrett Rollins, MD, PhD, and Janina Longtine, MD, of Brigham and Women’s Hospital, (top photo) as well as Monica Bertagnolli, MD, of Brigham and Women’s Hospital and Philip Kantoff, MD, from Dana-Farber (bottom photo).
Overview
Physicians, researchers, and scientists at Dana-Farber Cancer Institute and Brigham and Women’s Hospital have recently launched Profile, one of the nation’s most comprehensive personalized cancer medicine initiatives. This study currently involves the analysis of 471 somatic mutations in 41 genes using OncoMap, a modification of Sequenom’s mass spectrometry platform, with planned transition to next generation sequencing.
The study has already enrolled more than 1,500 patients, with approximately 10,000 patients expected to be enrolled by consent over the next 12 months. The test, which is performed on solid tumors, bone marrow, or blood samples, identifies most of the genetic mutations currently implicated in cancer development and growth today.
All of the more than 16,000 cancer patients who come to Dana-Farber and Brigham and Women’s Hospital for treatment each year are eligible to participate in this study. Pediatric patients will be eligible to participate in the near future. Screening is performed at the Brigham and Women’s Hospital Center for Advanced Molecular Diagnostics, a CLIA-certified laboratory.
Objectives
Profile aims to detect genetic alterations in tumors and potentially identify targeted therapies that are most likely to be effective in individual patients. The database of tumor genomic profiling data derived from a very large number of patients linked to clinical information makes Profile a powerful tool for discovery and personalized cancer medicine. This database, which adheres to emerging IT standards, also will support proposals for new research studies and clinical trials.
Future developments
To accommodate this constantly evolving field, the study’s platform is designed to scale up to include additional screening for new mutations as they are discovered. Germline genotyping is expected in the future. Whole exome sequencing and then whole genome sequencing also will become part of this program.
A history of genetic discoveries
Over the past decade, our physicians, researchers, and scientists have been at the forefront of personalized cancer medicine discoveries. As a result, targeted therapies have become the standard of care in multiple types of cancer, including colorectal cancer, lung cancer, and breast cancer. These include EGFR and ALK discoveries in lung cancer, triple negative and HER2-postive breast cancers, and KRAS, BRAF and PIK3CA in colorectal cancer.
Our personalized cancer medicine discoveries
EGFR mutations are detected comparably in cytologic and surgical pathology specimens of nonsmall cell lung cancer. Cancer Cytopathol. 2009 Feb 25;117(1):67-72
Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010; 363:1693-1703
Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell. 2010 Jan 19;17(1):77-88
Novel mutant-selective EGFR kinase inhibitors against EGFR T790M. Nature. 2009 Dec 24;462(7276):1070-4
Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature. 2008 Oct 16;455(7215):975-8.
EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304:1497-500.
Colorectal cancer
Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer. 2009 Aug 4;101(3): 465-72
Breast cancer
Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. Journal of Clinical Oncology. (JCO June 1, 2010 vol. 28 no. 16 2698-2704
Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancer. Br J Cancer. 2010 May 11;102(10):1495-502