bims-ovdlit 2023-07-23 papers

Issue of 2023–07–23
two papers selected by
Lara Paracchini, Humanitas Research

Nat Commun. 2023 Jul 20. 14(1): 4387

The copy number and mutational landscape of recurrent ovarian high-grade serous carcinoma.

BriTROC Investigators

The drivers of recurrence and resistance in ovarian high grade serous carcinoma remain unclear. We investigate the acquisition of resistance by collecting tumour biopsies from a cohort of 276 women with relapsed ovarian high grade serous carcinoma in the BriTROC-1 study. Panel sequencing shows close concordance between diagnosis and relapse, with only four discordant cases. There is also very strong concordance in copy number between diagnosis and relapse, with no significant difference in purity, ploidy or focal somatic copy number alterations, even when stratified by platinum sensitivity or prior chemotherapy lines. Copy number signatures are strongly correlated with immune cell infiltration, whilst diagnosis samples from patients with primary platinum resistance have increased rates of CCNE1 and KRAS amplification and copy number signature 1 exposure. Our data show that the ovarian high grade serous carcinoma genome is remarkably stable between diagnosis and relapse and acquired chemotherapy resistance does not select for common copy number drivers.

DOI: https://doi.org/10.1038/s41467-023-39867-7

Cancer Drug Resist. 2023 ;6(2): 358-377

Immune checkpoint inhibitors in ovarian cancer: where do we go from here?

Won-Hee Yoon, Anna DeFazio, Lawrence Kasherman.

Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy, and despite advancements in therapeutics, most women unfortunately still succumb to their disease. Immunotherapies, in particular immune checkpoint inhibitors (ICI), have been therapeutically transformative in many tumour types, including gynaecological malignancies such as cervical and endometrial cancer. Unfortunately, these therapeutic successes have not been mirrored in ovarian cancer clinical studies. This review provides an overview of the ovarian tumour microenvironment (TME), particularly factors associated with survival, and explores current research into immunotherapeutic strategies in EOC, with an exploratory focus on novel therapeutics in navigating drug resistance.

Keywords: Ovarian cancer; drug development; immunotherapy; tumour microenvironment

DOI: https://doi.org/10.20517/cdr.2023.13