Targeting cell survival proteins for cancer cell death

Manoj K. Pandey, Sahdeo Prasad, Amit Kumar Tyagi, Lokesh Deb, Jiamin Huang, Deepkamal N. Karelia, Shantu Amin, Bharat B. Aggarwal

Research output: Contribution to journalReview article

21 Citations (Scopus)

Abstract

Escaping from cell death is one of the adaptations that enable cancer cells to stave off anticancer therapies. The key players in avoiding apoptosis are collectively known as survival proteins. Survival proteins comprise the Bcl-2, inhibitor of apoptosis (IAP), and heat shock protein (HSP) families. The aberrant expression of these proteins is associated with a range of biological activities that promote cancer cell survival, proliferation, and resistance to therapy. Several therapeutic strategies that target survival proteins are based on mimicking BH3 domains or the IAP-binding motif or competing with ATP for the Hsp90 ATP-binding pocket. Alternative strategies, including use of nutraceuticals, transcriptional repression, and antisense oligonucleotides, provide options to target survival proteins. This review focuses on the role of survival proteins in chemoresistance and current therapeutic strategies in preclinical or clinical trials that target survival protein signaling pathways. Recent approaches to target survival proteins-including nutraceuticals, small-molecule inhibitors, peptides, and Bcl-2-specific mimetic are explored. Therapeutic inventions targeting survival proteins are promising strategies to inhibit cancer cell survival and chemoresistance. However, complete eradication of resistance is a distant dream. For a successful clinical outcome, pretreatment with novel survival protein inhibitors alone or in combination with conventional therapies holds great promise.

Original languageEnglish (US)
Article number11
JournalPharmaceuticals
Volume9
Issue number1
DOIs
StatePublished - Mar 1 2016

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Cell Survival
Cell Death
Neoplasms
Proteins
Apoptosis
Dietary Supplements
Therapeutics
Adenosine Triphosphate
Antisense Oligonucleotides
Protein Transport
Heat-Shock Proteins
Cell Proliferation
Clinical Trials
Peptides

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmaceutical Science

Cite this

Pandey, M. K., Prasad, S., Tyagi, A. K., Deb, L., Huang, J., Karelia, D. N., ... Aggarwal, B. B. (2016). Targeting cell survival proteins for cancer cell death. Pharmaceuticals, 9(1), [11]. https://doi.org/10.3390/ph9010011
Pandey, Manoj K. ; Prasad, Sahdeo ; Tyagi, Amit Kumar ; Deb, Lokesh ; Huang, Jiamin ; Karelia, Deepkamal N. ; Amin, Shantu ; Aggarwal, Bharat B. / Targeting cell survival proteins for cancer cell death. In: Pharmaceuticals. 2016 ; Vol. 9, No. 1.
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Pandey, MK, Prasad, S, Tyagi, AK, Deb, L, Huang, J, Karelia, DN, Amin, S & Aggarwal, BB 2016, 'Targeting cell survival proteins for cancer cell death', Pharmaceuticals, vol. 9, no. 1, 11. https://doi.org/10.3390/ph9010011

Targeting cell survival proteins for cancer cell death. / Pandey, Manoj K.; Prasad, Sahdeo; Tyagi, Amit Kumar; Deb, Lokesh; Huang, Jiamin; Karelia, Deepkamal N.; Amin, Shantu; Aggarwal, Bharat B.

In: Pharmaceuticals, Vol. 9, No. 1, 11, 01.03.2016.

Research output: Contribution to journalReview article

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Pandey MK, Prasad S, Tyagi AK, Deb L, Huang J, Karelia DN et al. Targeting cell survival proteins for cancer cell death. Pharmaceuticals. 2016 Mar 1;9(1). 11. https://doi.org/10.3390/ph9010011