Alternative approaches to overcome chemoresistance to apoptosis in cancer

Adv Protein Chem Struct Biol. 2021:126:91-122. doi: 10.1016/bs.apcsb.2021.01.005. Epub 2021 Mar 9.


Apoptosis, or programmed cell death, is a form of regulated cell death (RCD) that is essential for organogenesis and homeostatic maintenance of normal cell populations. Apoptotic stimuli activate the intrinsic and/or extrinsic pathways to induce cell death due to perturbations in the intracellular and extracellular microenvironments, respectively. In patients with cancer, the induction of apoptosis by anticancer drugs and radiation can produce cancer cell death. However, tumor cells can adapt and become refractory to apoptosis-inducing therapies, resulting in the development of clinical resistance to apoptosis. Drug resistance facilitates the development of aggressive primary tumors that eventually metastasize, leading to therapy failure and mortality. To overcome the resistance to apoptosis to neoadjuvant chemotherapy or targeted therapy, alternative targets of RCD can be induced in apoptosis-resistant cancer cells. Alternatively, cell death can be independent of apoptosis and this strategy could be utilized to develop novel anti-cancer therapies. This chapter discusses approaches that could be employed to overcome clinical resistance to apoptosis in cancer cells.

Keywords: Apoptosis; Apoptosis resistance; Cancer; Cell death; Non-apoptotic cell death; Regulated cell death.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Drug Resistance, Neoplasm / immunology*
  • Humans
  • Neoadjuvant Therapy*
  • Neoplasm Metastasis
  • Neoplasms* / immunology
  • Neoplasms* / pathology
  • Neoplasms* / therapy