Mitochondrial integration and ovarian cancer chemotherapy resistance

Exp Cell Res. 2021 Apr 15;401(2):112549. doi: 10.1016/j.yexcr.2021.112549. Epub 2021 Feb 26.

Abstract

Ovarian cancer has been nicknamed the "silent killer". Most patients with ovarian cancer are diagnosed at an advanced stage of the disease for the first time because of its insignificant early clinical symptoms. In addition to the difficulty of early screening and delay in diagnosis, the high recurrence rate and relapsed refractory status of patients with ovarian cancer are also important factors for their high mortality. Patients with recurrent ovarian cancer often use neoadjuvant chemotherapy followed by surgery as the first choice. However, this is often accompanied by chemotherapy resistance, leading to treatment failure and a mortality rate of more than 90%. In the past, it was believed that the anti-tumor effect of chemotherapeutics represented by cisplatin was entirely attributable to its irreversible damage to DNA, but current research has found that it can inhibit cell growth and cytotoxicity via nuclear and cytoplasmic coordinated integration. As an important hub and integration platform for intracellular signal communication, mitochondria are responsible for multiple key factors during tumor occurrence and development, such as metabolic reprogramming, acquisition of metastatic ability, and chemotherapy drug response. The role of mitochondria in ovarian cancer chemotherapy resistance is becoming increasingly recognized. In this review, we discuss the cellular interactive regulatory network surrounding mitochondria, elucidate the mechanisms of tumor cell survival under chemotherapy, and discuss potential means of interfering with mitochondrial function as a novel anti-cancer therapy.

Keywords: Apoptosis; Autophagy; Chemotherapy resistance; Integration response; Mitochondria; Organelle interaction; Ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Cell Proliferation / drug effects*
  • Cisplatin / adverse effects
  • Cisplatin / therapeutic use
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Humans
  • Mitochondria / genetics*
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Signal Transduction / drug effects

Substances

  • Cisplatin