Geoffrey Ira Shapiro

DNA-PK enforces the S/G2 checkpoint in ATM-deficient cells to limit ATR inhibitor efficacy

This study shows DNA-PK enforces the S/G2 checkpoint in ATM-deficient cells, reducing ATR inhibitor efficacy, and suggests combining ATR and DNA-PK inhibition could enhance treatment in such cancers.

TALAVE in Breast Cancer: BRCA1/2 Mutation-Dependent Immune Remodeling after PARP Inhibition with Limited Checkpoint Engagement

The paper shows BRCA-mutant breast cancers respond to PARP inhibitors with immune remodeling, but PD-L1 blockade is ineffective due to spatial separation of PD-L1+ cells and PD-1+ T cells.

BET BD2 inhibition facilitates SPOP-mediated degradation of chromatin-associated BRD4/BRD4-NUT, a therapeutic vulnerability in NUT carcinoma

The paper shows that selective inhibition of BRD4-BD2 promotes SPOP-mediated degradation of BRD4/BRD4-NUT in NUT carcinoma, leading to better therapeutic outcomes than pan-BET inhibition.

Defective Microhomology-Mediated End-joining in SMARCB1-Deficient Tumors

This study identifies a defect in MMEJ repair in SMARCB1-deficient tumors, leading to hyper-dependence on the FA/BRCA pathway, which can be targeted for therapy.

Disruption of Microhomology-mediated End-joining in Ewing Sarcoma

This paper shows that Ewing sarcoma cells have reduced POLθ expression and MMEJ activity due to EWS-FLI1 or EWSR1 disruption, making them sensitive to inhibitors of FA, NHEJ, or HR pathways.

Targeting FGFR signaling overcomes therapeutic resistance and immune evasion in oncogenic PIK3CA-driven serous-like endometrial cancer

This study identifies FGFR signaling as a driver of resistance and immune evasion in PIK3CA-driven serous-like endometrial cancer and shows that dual FGFR/PI3K inhibition improves tumor control.

AI-Enhanced Adaptive Virtual Screening Platform Enabling Exploration of 69 Billion Molecules Discovers Structurally Validated FSP1 Inhibitors

AdaptiveFlow enables large-scale virtual screening of 69 billion molecules to discover validated FSP1 inhibitors, improving efficiency and scalability in drug discovery.

MatchMiner: An open source computational platform for real-time matching of cancer patients to precision medicine clinical trials using genomic and clinical criteria

MatchMiner automates matching cancer patients to precision medicine trials using genomic and clinical criteria, enabling efficient and accurate trial enrollment.