Polycomb Repressor Complex 1 (PRC1) in ovarian cancer: a scoping literature review.

in Critical reviews in oncology/hematology by Jessica Floyd, Kristen Desanto, Benjamin G Bitler, Lindsay W Brubaker

TLDR

  • The study is about a type of cancer called high grade serous carcinoma (HGSC) and how it can be treated. HGSC is a type of ovarian cancer that is hard to treat and often comes back. The study looked at a group of proteins called Polycomb Repressor Complexes 1 and 2 (PRC1/2) that may be involved in the development and recurrence of HGSC. The study found that these proteins can help cancer cells become resistant to treatment. The study also found that targeting these proteins could be a promising way to treat HGSC. However, the study needs more research to fully understand how these proteins work and to find new ways to treat HGSC.

Abstract

High grade serous carcinoma (HGSC) is the most common and the deadliest histologic subtype of epithelial ovarian cancer. HGSC is a therapeutic challenge, as it recurs in 80% of patients diagnosed, often as chemoresistant disease. The mechanism of this chemoresistance is not fully elucidated, but it is partly attributed to the ability of HGSC to maintain a stem-like phenotype that enables development of resistance to current therapies. Polycomb Repressor Complexes 1 and 2 (PRC1/2) have been implicated in the maintenance of the stem cell compartment through silencing tumor suppressor genes and regulating stem cells. These complexes are comprised of multiple polycomb group (PcG) proteins that play a role in normal development, and when deregulated contribute to the development of cancer [2]. Proteins included in PRC1 include B lymphoma mouse Moloney leukemia virus insertion region (BMI1), RING1, and chromobox (CBX) proteins. We aimed to review each of the protein components of PRC1 and their mechanistic relationships to promoting chemoresistant recurrences and propagation of ovarian cancer. Where possible, we reviewed therapeutic investigations of these proteins. We utilized a scoping literature review through Covidence to identify 42 articles meeting criteria for inclusion. The authors identified four relevant articles and the Yale MeSH Analysis Grid Generator was used to establish additional keywords and heading terms. A medical librarian used these terms and articles to draft an initial search strategy within each of the following databases: MEDLINE, Embase, Cochrane Library, and Web of Science Core Collection, yielding 439 articles based on title and abstract. Abstracts were independently reviewed by the authors, identifying 77 articles for full text review, of which 35 were ultimately excluded, leaving 42 articles for full review. Our review identified the currently known mechanisms of the subunits of PRC1 that contribute to HGSC development, recurrence, and chemoresistance. By compiling a comprehensive review of available scientific knowledge, we support and direct further investigation into PRC1 that can affect meaningful advances in the treatment of HGSC.

Overview

  • The study aims to review the protein components of Polycomb Repressor Complexes 1 and 2 (PRC1/2) and their mechanistic relationships to promoting chemoresistant recurrences and propagation of ovarian cancer. The authors utilized a scoping literature review through Covidence to identify 42 articles meeting criteria for inclusion. The review identified the currently known mechanisms of the subunits of PRC1 that contribute to HGSC development, recurrence, and chemoresistance. By compiling a comprehensive review of available scientific knowledge, the study supports and directs further investigation into PRC1 that can affect meaningful advances in the treatment of HGSC.

Comparative Analysis & Findings

  • The study identified four relevant articles and the Yale MeSH Analysis Grid Generator was used to establish additional keywords and heading terms. A medical librarian used these terms and articles to draft an initial search strategy within each of the following databases: MEDLINE, Embase, Cochrane Library, and Web of Science Core Collection, yielding 439 articles based on title and abstract. Abstracts were independently reviewed by the authors, identifying 77 articles for full text review, of which 35 were ultimately excluded, leaving 42 articles for full review. The review identified the currently known mechanisms of the subunits of PRC1 that contribute to HGSC development, recurrence, and chemoresistance.

Implications and Future Directions

  • The study's findings suggest that PRC1 plays a crucial role in the development and recurrence of HGSC, and that targeting PRC1 could be a promising therapeutic approach. However, the study also highlights the need for further research to fully understand the mechanisms of PRC1 and to identify new targets for therapy. Possible future research directions include investigating the role of PRC1 in the development of drug resistance and identifying new drugs that target PRC1. Additionally, the study suggests that a combination of PRC1 targeting and other therapies, such as immunotherapy, may be more effective in treating HGSC.
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