Evolution of Chemosensitivity and Resistance Assays as Predictors of Clinical Outcomes in Epithelial Ovarian Cancer Patients

Abstract

Epithelial ovarian cancer (EOC) is responsible for more cancer-related deaths than any other malignancy of the female reproductive system. The standard of care for advanced EOC involves a combination of cytoreductive surgery and platinum-based chemotherapy. Although a majority of patients respond to a platinum-containing regimen, many fail to respond to first-line treatment (platinum-refractory disease) or experience disease progression within 6 months of completing treatment (platinum-resistant disease). Even in patients who initially respond to platinum-based therapy, secondary development of platinum resistance is common. Many chemotherapeutic regimens with comparable efficacy and toxicities are available, leaving the determination of optimal therapy to the physician’s discretion. There have been many efforts over the years to develop accurate predictors of outcomes in patients treated with chemotherapy to help inform treatment decisions. Predictive treatment markers are particularly relevant in a disease such as EOC, where a large number of similarly efficacious chemotherapy regimens are available. Chemosensitivity and resistance assays (CSRAs) are attractive approaches to interrogate the efficacy and complex biology of EOC. Some early predictive cellular tests, such as the early clonogenic assays, were limited by technical and logistical issues. Over time, changes in these assays have improved their prognostic and predictive value, but there is still a lack of widespread adoption due to methodological difficulties or limited clinical validation. Herein, we provide an overview of the evolution of CSRAs used to predict outcomes in patients treated with chemotherapy that have been evaluated for use in EOC, with a focus on the latest generation chemoresponse assay.

ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease

“…Thus, resistance to platinum-based treatment is common, with roughly 20% of women experiencing disease progression 6 months after completing a platinum-based regimen (previously classified as 'platinum-resistant' relapse) or who fail to respond at all to first-line treatment or relapse within 4-6 weeks after last platinum dose (previously classified as 'platinum-refractory') [43]. There have been many efforts over the years to develop accurate predictors of outcomes in patients treated with chemotherapy to help inform treatment decisions [44].…”

“…For SOLO2 [36], TFST analysis was preplanned and showed an additional advantage of 7.2 months, comparing the difference between the median TFST and PFS for patients who received olaparib compared with placebo. In the NOVA and ARIEL3 trials [43,44], PARP inhibitor treatment was discontinued upon progression. Currently, the recommended length of PARP inhibitor treatment, based on these results, remains unclear.…”

Current Approaches for Personalized Therapy of Soft Tissue Sarcomas

“…It refers to the identification of antisarcoma activity of individual drugs or drug combinations using cell-or tissue-based models: chemosensitivity and resistance assays (CSRA). e development of CSRA was started in 1970s for identification of anticancer drugs for individual patients, and the first assays were based on colony-forming efficiency of tumor-derived cells in the presence of various drugs [8,9]. Furthermore, CSRA were incorporated in a variety of detection systems but shared similar principles and general procedures: (a) tumor cells were isolated and established in an in vitro medium; (b) cells were incubated with the chemotherapeutic agent(s) of interest; (c) cell survival (or death) was assessed; and (d) a report detailing sensitivity and/or resistance to tested drugs was generated.…”

Low expression of NCALD is associated with chemotherapy resistance and poor prognosis in epithelial ovarian cancer

“…However, chemotherapy resistance in the later stage of treatment results in high recurrence, metastasis and mortality [4,5]. Current prognostic indicators including age, stage, and histological type are insufficient to predict the efficacy of conventional chemotherapy [6,7]. In order to improve the prognosis of ovarian cancer patients, new biomarkers which predict chemotherapy resistance and treatment strategies to overcome resistance are needed.…”