Mutations in DNA repair genes are known drivers of hereditary cancers. However, only a small fraction of patients with hereditary breast or ovarian cancers has BRCA1/2 mutations, which are involved in homologous recombination (HR) DNA repair. Researchers led by Nidhi Sahni, Ph.D., calculated scores across tumors from The Cancer Genome Atlas to comprehensively identify tumors that were either positive or negative for HR defects. Around 75% of tumors with a positive HR score did not have defects in known HR genes,...

The immune checkpoint inhibitor avelumab has been approved for multiple cancer types, but has thus far had mixed results in gynecologic patients. A study led by Aung Naing, M.D., was designed to evaluate whether combining avelumab with a 4-1BB agonist (utomilumab), an OX40 agonist (PF-04518600) or radiotherapy would increase efficacy. Although the combinations proved to be safe, they did not produce significant responses in this heavily pretreated population. In 35 patients evaluated, the overall response rate (ORR) was 2.9% and...

The human genome contains thousands of non-canonical open reading frames (ORFs) with the potential to encode functional proteins, including microproteins. These unannotated, cryptic proteins are not easily detected by conventional approaches and are considered part of the “dark” proteome. Previous studies have highlighted the tumor-suppressive function of some microproteins in colorectal cancer (CRC), but their role in cancer remains largely unknown. To provide further insights, researchers led by Yiwen Chen, Ph.D., used an integrated multiomic approach combining ribosome...