Survivin-Based Treatment Strategies for Squamous Cell Carcinoma

Int J Mol Sci. 2018 Mar 24;19(4):971. doi: 10.3390/ijms19040971.

Abstract

Survivin, an anti-apoptotic molecule abundantly expressed in most human neoplasms, has been reported to contribute to cancer initiation and drug resistance in a wide variety of human tumors. Efficient downregulation of survivin can sensitize tumor cells to various therapeutic interventions, generating considerable efforts in its validation as a new target in cancer therapy. This review thoroughly analyzes up-to-date information on the potential of survivin as a therapeutic target for new anticancer treatments. The literature dealing with the therapeutic targeting of survivin will be reviewed, discussing specifically squamous cell carcinomas (SCCs), and with emphasis on the last clinical trials. This review gives insight into the recent developments undertaken in validating various treatment strategies that target survivin in SCCs and analyze the translational possibility, identifying those strategies that seem to be the closest to being incorporated into clinical practice. The most recent developments, such as dominant-negative survivin mutants, RNA interference, anti-sense oligonucleotides, small-molecule inhibitors, and peptide-based immunotherapy, seem to be helpful for effectively downregulating survivin expression and reducing tumor growth potential, increasing the apoptotic rate, and sensitizing tumor cells to chemo- and radiotherapy. However, selective and efficient targeting of survivin in clinical trials still poses a major challenge.

Keywords: inhibitor of apoptosis; oral squamous cell carcinoma; squamous cell carcinoma; survivin.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Cell Proliferation / drug effects
  • Clinical Trials as Topic
  • Genetic Therapy / methods
  • Humans
  • Immunotherapy / methods
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors*
  • Inhibitor of Apoptosis Proteins / genetics
  • Mice
  • Molecular Targeted Therapy / methods*
  • Mouth Neoplasms / pathology
  • Mouth Neoplasms / therapy*
  • Oligonucleotides, Antisense / therapeutic use
  • RNA Interference
  • Survivin
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Oligonucleotides, Antisense
  • Survivin