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The evolving role of DNA damage response in overcoming therapeutic resistance in ovarian cancer

Cancer Drug Resistance 2023年第2期6卷 345-357页

作者： Sara Bouberhan Liron Bar-Peled yusuke matoba.varvara mazina Lauren Philp Bo R.eda Division of Hematology/Oncology Department of MedicineMassachusetts General HospitalBostonMA 02114USA Department of Medicine Harvard Medical SchoolBostonMA 02115USA Center for Cancer Research Massachusetts General HospitalBostonMA 02114USA Department of Obstetrics and Gynecology Vincent Center for Reproductive BiologyMassachusetts General HospitalBostonMA 02114USA Obstetrics Gynecologyand Reproductive BiologyHarvard Medical SchoolBostonMA 02115 USA Division of Gynecologic Oncology Department of Obstetrics and GynecologyMassachusetts General HospitalBostonMA 02114USA

Epithelial ovarian cancer(EOC)is treated in the first-line setting with combined platinum and taxane chemotherapy,often followed by a maintenance poly(ADP-ribose)polymerase inhibitor(PARPi).Responses to first-line treatment are *** many patients,however,responses are suboptimal or *** the last several years,multiple new classes of agents targeting DNA damage response(DDR)mechanisms have advanced through clinical *** this review,we explore the preclinical rationale for the use of ATR inhibitors,CHK1 inhibitors,and WEE1 inhibitors,emphasizing their application to chemotherapy-resistant and PARPi-resistant ovarian *** also present an overview of the clinical development of the leading drugs in each of these classes,emphasizing the rationale for monotherapy and combination therapy approaches.

关键词： Ovarian cancer platinum resistance PARPi resistance DDR

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Difficult Conversations and Painful Decisions: When Should Patients with Progressive Cancer Stop Chemotherapy?

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Journal of Cancer Therapy 2022年第1期13卷 20-47页

作者： Jeanine Staples varvara mazina Bethany-Rose Daubman Annekathryn Goodman Sibley Memorial Hospital Johns Hopkins Medicine Sibley Center for Gynecologic Oncology and Advanced Pelvic Surgery ashington USA Massachusetts General Hospital Harvard Medical School Division of Gynecologic Oncology Boston USA Massachusetts General Hospital Harvard Medical School Division of Palliative Care and Geriatric Medicine Boston USA

Introduction: The decision to stop anti-cancer treatment is fraught with many challenges for the oncologist, the patient, and their caregivers. This review examines the special considerations surrounding the decision to cease chemotherapy in terminally ill cancer patient. Methods: A comprehensive literature search was conducted to find relevant publications on chemotherapy cessation. A total of 2700 records were retrieved and 141 were identified as eligible for inclusion in this review. Results: Palliative chemotherapy does not achieve the goal of tumor-related symptom reduction for patients who have experienced progressive disease with more than two prior lines of chemotherapy. ECOG performance status is a crucial predictor of response to therapy and chemotherapy-related complications. Challenges to stopping chemotherapy at the end of life are multifactorial and are both patient and physician-driven. Racial, ethnic, and income-based disparities are seen in the timing and quality of end-of-life conversations offered by physicians to their patients. Conclusions: The decision to cease chemotherapy is one that should be approached with careful consideration and accurate information. Clear communication, compassion and empathy are important components to the therapeutic relationship. Early involvement of palliative care and clear conversations about prognosis and the expected utility of further chemotherapy is essential to conduct the best possible care for cancer patients at the end of life.

关键词： Chemotherapy Chemotherapy Resistance Chemotherapy Cessation Palliative Chemotherapy Recurrent Cancer and Prognosis Best Supportive Care Medical Futility End-of-Life

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