Chemoresistance in ovarian cancer (I)
Peng-Hui Wang, Szu-Ting Yang, Chia‐Hao Liu, Che-Wei Chang, Brahmana Askandar Tjokroprawiro
Abstract
Epithelial ovarian cancer (OC) presents unique challenges in diagnosis and treatment, characterized by vague symptoms and signs, delayed diagnosis and frequent advanced stage (ad). Initial the standard of care (SOC) treatment includes intensive cytoreductive surgery (CRS) and platinum-paclitaxel chemotherapy with/without adding anti-angiogenetic agent and/or following poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) maintenance therapy based on biomarker-guided recommendation, such as BRCA mutation and/or homologous recombination deficiency (HRD significance). However, OC-associated high recurrence rates and development of chemoresistance to recurrent OC (rOC) result in the therapeutic failure and subsequent fatal outcomes. All suggest the current treatment for platinum-resistant rOC (PR-rOC) patients is clinically unmet. Therefore, better understandings of underlying mechanisms and molecular changes of cancer cells may offer hints to overcome the chemoresistance in OC. Chemoresistance may be derived from "naïve" (underlying or primary) hereditary or acquired adaption (secondary or induced), which are involved in an increasing ability to self-repairing DNA, dysregulated autophagy process and evasion of apoptosis and alternation in mitochondrial pathways as well as metabolic adaptions, changing signaling pathway for proliferation and survival, and modifying genetic and epigenetic resolution, contributing to sustaining proliferative signaling, resisting cell death, evading growth suppressor, inducing angiogenesis, activating invasion and metastases, deregulating cellular energetics, reaching cellular senescence and stemness, and epigenetic reprogramming of cancer cells. The first part is a brief review for PR-rOC, including mechanisms, and combating strategies but only limited to cytoreductive surgery for treating PR-rOC patients.