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Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2).

Author: AghajanianCarol, ChambersSetsuko K, ChenLee-May, ColemanRobert L, DobrovicAlexander, DominyErin, DorigoOliver, ElvinJulia A, GhatagePrafull, GiordanoHeidi, GobleSandra, HardingThomas, KaufmannScott H, KonecnyGottfried E, KristeleitRebecca S, KwanTanya T, LearyAlexandra, LinDouglas I, LinKevin K, MaLing, MaloneyLara, McNeishIain A, MusaferAshan, O'MalleyDavid M, OakninAna, OzaAmit M, ProvencherDiane, Ray-CoquardIsabelle, ScottClare L, SwisherElizabeth M, TinkerAnna V, VoLan-Thanh, Wahner HendricksonAndrea E, WelchStephen

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Overview

Rucaparib, a PARP inhibitor, showed promising efficacy in patients with relapsed high-grade ovarian carcinoma who had previously received platinum-based chemotherapy. Mutations in RAD51C, RAD51D, and high-level BRCA1 promoter methylation were associated with response to rucaparib. BRCA1 methylation loss might be a key factor in developing resistance to platinum and PARP inhibitors. This study suggests that rucaparib may be an effective treatment option for patients with relapsed ovarian cancer who have certain genetic markers.
Paper Details　
Original Abstract of the Article :
ARIEL2 (NCT01891344) is a single-arm, open-label phase 2 study of the PARP inhibitor (PARPi) rucaparib in relapsed high-grade ovarian carcinoma. In this post hoc exploratory biomarker analysis of pre- and post-platinum ARIEL2 samples, RAD51C and RAD51D mutations and high-level BRCA1 promoter methyla...See full text at original site
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引用元：
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093258/

データ提供：米国国立医学図書館（NLM）

Deciphering the Secrets of Rucaparib in Ovarian Cancer: A Biomarker Odyssey

In the realm of ovarian cancer research, the search for effective treatments continues. This study embarked on a biomarker odyssey, exploring the molecular landscape of ovarian cancer in patients undergoing treatment with rucaparib, a PARP inhibitor. They sought to identify the molecular markers that predict a patient's response to this therapy, like navigating a treacherous desert with a map and compass.

Mapping the Terrain: Predicting Response and Resistance

The researchers unearthed a treasure trove of insights: mutations in RAD51C and RAD51D, as well as high-level BRCA1 promoter methylation, emerged as reliable predictors of response to rucaparib. Furthermore, they discovered that BRCA1 methylation loss could be a key factor driving resistance to both platinum-based chemotherapy and rucaparib. These findings shed light on the intricate mechanisms of response and resistance, guiding future treatment strategies.

The Path Forward: Precision Medicine

This research underscores the critical role of biomarkers in guiding personalized treatment strategies. By identifying patients who are most likely to benefit from rucaparib, we can tailor therapies and improve outcomes. This approach, known as precision medicine, helps us navigate the complex landscape of ovarian cancer treatment with greater precision and hope.

Dr. Camel's Conclusion

The researchers have navigated a complex landscape, mapping the terrain of ovarian cancer treatment. These findings offer valuable insights into the mechanisms of response and resistance to rucaparib, paving the way for more personalized and effective therapies for patients with this challenging disease.

Date :
  1. Date Completed 2021-05-20
  2. Date Revised 2022-03-02
Further Info :

Pubmed ID

33941784

DOI: Digital Object Identifier

PMC8093258

Related Literature

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・Effects of rucaparib
SNS
PICO Info
in preparation
Languages

English

Positive IndicatorAn AI analysis index that serves as a benchmark for how positive the results of the study are. Note that it is a benchmark and requires careful interpretation and consideration of different perspectives.

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