Evolutionary Medicine May Provide Clues for Cancer Genetics

Maurie Markman, MD
Published: Friday, Jun 28, 2019
Maurie Markman, MD

Maurie Markman, MD
Long before the explosion of molecular data about germline abnormalities or variants that can increase the lifetime risk for developing a malignancy, physicians were taught the importance of obtaining a detailed family history from their patients to learn about the potential for a genetic risk. Classic examples of the value of such knowledge include the development of epithelial ovarian cancer or early onset breast cancer in several generations or the documentation of colon cancer in members of a family at a young age.

Today, with the routine performance of single gene or germline panel testing, as well as a critical focus on prospective follow-up of individuals with incompletely understood germline variants, clinicians are developing an increasingly robust appreciation for the influence of an individual’s genetic background on the likelihood of developing specific malignancies or a group of malignant conditions.

In the case of the BRCA genes, the relevance of this knowledge has extended beyond individual risk projections into evidence-based recommendations for strategies to favorably affect that risk (eg, prophylactic oophorectomy, mastectomy) or to increase cancer-related surveillance. More recently, the presence of BRCA mutations in women with ovarian or breast cancer has led to the use of targeted therapeutic agents (PARP inhibitors) to influence mechanisms of the molecular abnormalities. Knowledge of the relevance of germline events that influence the risk of future cancer for an individual or family member, or that may be exploited to achieve a successful therapeutic outcome, has led to an increase in basic and translational laboratory investigations as well as clinical trials. Research teams are actively exploring mechanisms of resistance to PARP inhibitors, such as the functional reversion of a BRCA-mutant state to a wild-type state and the combination of this class of drugs with other antineoplastic strategies, such as checkpoint inhibitors.

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Online CME Activities
TitleExpiration DateCME Credits
Oncology Briefings™: Individualizing Treatment After Second-Line Therapy for Patients With mCRCAug 29, 20191.0
Community Practice Connections™: Immunotherapeutic Strategies with the Potential to Transform Treatment for Genitourinary CancersAug 29, 20191.0
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