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Last Posted: Feb 02, 2023
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Pancreatic Cancer: Beyond Brca Mutations
V Ricci et al, J Per Med, December 16, 2022

Pancreatic cancer is the fourth-leading cause of cancer-related deaths worldwide. The outcomes in patients with pancreatic cancer remain unsatisfactory. In the current review, we summarize the genetic and epigenetic architecture of metastatic pancreatic cancer beyond the BRCA mutations, focusing on the genetic alterations and the molecular pathology in pancreatic cancer. This review focuses on the molecular targets for the treatment of pancreatic cancer, with a correlation to future treatments. The potential approach addressed in this review may lead to the identification of a subset of patients with specific biological behaviors and treatment responses.

Combining PARP Inhibitor With Immunotherapy-Does the Promise of Preclinical Data Translate to Clinic?
Thawani Rajat et al. JAMA oncology 2022 11

Results from two recent trials warrant further investigation into the underlying biology that resulted in lack of clinical benefit of the study drug combination in the majority of patients with non–BRCA-associated cancers, and apparent lack of improved clinical benefit compared with single agent alone in BRCA-associated cancers.

Avelumab Plus Talazoparib in Patients With BRCA1/2- or ATM-Altered Advanced Solid Tumors: Results From JAVELIN BRCA/ATM, an Open-Label, Multicenter, Phase 2b, Tumor-Agnostic Trial.
Schram Alison M et al. JAMA oncology 2022 11

Is the combination of avelumab and talazoparib effective in patients with pathogenic BRCA1/2 or ATM alterations, regardless of tumor type? In this phase 2b nonrandomized controlled trial with 200 patients, neither the BRCA1/2 nor ATM cohort met the prespecified target of an objective response rate of 40% across cancer types. Durable clinical activity was observed in patients with BRCA1/2-associated tumor types (eg, ovarian, breast, prostate, and pancreatic cancers) vs those with non–BRCA-associated cancer types; a notable exception were patients with BRCA1/2-altered uterine leiomyosarcoma, who had prolonged responses to treatment.

Proband-mediated interventions to increase disclosure of genetic risk in families with a BRCA or Lynch syndrome condition: a systematic review
AL Young et al, EJHG, October 17, 2022

Intervention delivery modes included genetic counselling with additional telephone or in-person follow-up, letters, videos, and decision aids. The percentages of at-risk relatives informed by the proband about their risk ranged from 54.0% to 95.5% in the intervention or family-mediated comparison group. Of those who were informed, 24.4–60.0% contacted a genetics clinic and 22.8–76.2% had genetic testing after they were counselled at a genetics clinic.

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Disclaimer: Articles listed in the Public Health Genomics and Precision Health Knowledge Base are selected by the CDC Office of Public Health Genomics to provide current awareness of the literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the update, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.

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