Tina Roy

Georgetown University Medical Center

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Aiwu Ruth He

Georgetown University

Martin C. Tammemägi

Brock University

Chao Yin

Ocean University of China

Paul Sackstein

Georgetown University Medical Center

Samuel A. Kareff

Sylvester Comprehensive Cancer Center

George Luta

Georgetown University

Brennan Decker

Foundation Medicine (United States)

Reena Jha

Georgetown University

Randi M. Williams

Georgetown University Medical Center

Kathryn L. Taylor

Georgetown University

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Georgetown University

Georgetown University Medical Center

MedStar Georgetown University Hospital

Georgetown Lombardi Comprehensive Cancer Center

Foundation Medicine (United States)

Vince Lombardi Cancer Clinic

Memorial Sloan Kettering Cancer Center

Houston Methodist

Western University

Chongqing Medical University

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Homologous Recombination Repair in Biliary Tract Cancers: A Prime Target for PARP Inhibition?

Cancers (2022)

Chao Yin Monika Kulasekaran Tina Roy Brennan Decker Sonja Alexander

Biliary tract cancers (BTCs) are a heterogeneous group of malignancies that make up ~7% of all gastrointestinal tumors. It is notably aggressive and difficult to treat; in fact, >70% of patients with BTC are diagnosed at an advanced, unresectable stage and are not amenable to curative therapy. For these patients, chemotherapy has been the mainstay treatment, providing an inadequate overall survival of less than one year. Despite the boom in targeted therapies over the past decade, only a few targeted agents have been approved in BTCs (i.e., IDH1 and FGFR inhibitors), perhaps in part due to its relatively low incidence. This review will explore current data on PARP inhibitors (PARPi) used in homologous recombination deficiency (HRD), particularly with respect to BTCs. Greater than 28% of BTC cases harbor mutations in genes involved in homologous recombination repair (HRR). We will summarize the mechanisms for PARPi and its role in synthetic lethality and describe select genes in the HRR pathway contributing to HRD. We will provide our rationale for expanding patient eligibility for PARPi use based on literature and anecdotal evidence pertaining to mutations in HRR genes, such as RAD51C, and the potential use of reliable surrogate markers of HRD.

Synthetic Lethality

10.3390/cancers14102561

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Race & sex disparities related to low-dose computed tomography lung cancer screening eligibility criteria: A lung cancer cases review

Lung Cancer (2022)

Randi M. Williams Samuel A. Kareff Paul Sackstein Tina Roy George Luta

10.1016/j.lungcan.2022.05.008

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Citations (5)