Research

Dana-Farber to Offer First CAR T-cell Therapy for Indolent Follicular Lymphoma Following FDA Approval

The U.S. Food and Drug Administration (FDA) has approved the CAR T-cell treatment axicabtagene ciloleucel (axi-cel or Yescarta) for patients with indolent follicular lymphoma, a slow growing, non-Hodgkin lymphoma (NHL). Axi-cel was approved as a standard treatment for patients with follicular lymphoma (FL) who have relapsed from, or become resistant to, other treatments. The approval of axi-cel is based on the results of the ZUMA-5 trial, a phase 2 study led by Caron Jacobson, MD, MMSc, and Dana-Farber investigators. Several CAR T-cell therapies, including axi-cel, have received FDA approval for the treatment of aggressive lymphomas, but axi-cel is the first to be approved for indolent forms of the disease ... 

MMB-FOXM1-Driven Premature Mitosis is Required for CHK1 Inhibitor Sensitivity (Cell)

Due to oncogene-driven acceleration of cell division, cancer cells may become hyper-dependent on the ATR-CHK1 pathway to manage replication stress and maintain sufficient genomic integrity for continued survival. Inhibitors of ATR and CHK1 have been developed as anti-cancer agents to exploit this vulnerability ... To identify genes whose monogenic loss confers resistance to the CHK1 inhibitor prexasertib, Timothy Branigan, PhD, and James DeCaprio, MD, led genome-wide CRISPR-Cas9 KO screenings in two non-small-cell lung cancer (NSCLC) cell lines (549 and NCI-H460) in the presence of cytotoxic concentrations of prexasertib ... 

Hotspot Mutation in Transcription Factor IKZF3 Drives B Cell Neoplasia via Transcriptional Dysregulation (Cancer Cell)

Hotspot mutation of IKZF3 (IKZF3-L162R) has been identified as a putative driver of chronic lymphocytic leukemia (CLL), but its function remains unknown. In a recent study in Cancer Cell, Gregory Lazarian, PhD, and Catherine Wu, MD, investigated its driving role in CLL using a B cell-restricted conditional knockin mouse model. Mutant Ikzf3 alters its normal DNA binding specificity and target selection, leading to hyperactivation of B cell receptor (BCR) signaling, overexpression of nuclear factor κB (NF-κB) target genes, and development of CLL-like disease in elderly mice with a penetrance of ~40% ... 

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