Vitamin A and Retinoids in Bladder Cancer Chemoprevention and Treatment: A Narrative Review of Current Evidence, Challenges and Future Prospects

Int J Mol Sci. 2021 Mar 29;22(7):3510. doi: 10.3390/ijms22073510.

Abstract

Bladder cancer (BC) is the tenth most common cancer worldwide with a high recurrence rate, morbidity and mortality. Therefore, chemoprevention and improved treatment of BC are of paramount importance. Epidemiological studies suggest that adequate vitamin A intake may be associated with reduced BC risk. In addition, retinoids, natural and synthetic derivatives of vitamin A, are intensively studied in cancer research due to their antioxidant properties and their ability to regulate cell growth, differentiation, and apoptosis. Findings from in vivo and in vitro models of BC show great potential for the use of retinoids in the chemoprevention and treatment of BC. However, translation to the clinical practice is limited. In this narrative review we discuss: (i) vitamin A and retinoid metabolism and retinoic acid signalling, (ii) the pathobiology of BC and the need for chemoprevention, (iii) the epidemiological evidence for the role of dietary vitamin A in BC, (iv) mechanistic insights obtained from in vivo and in vitro models, (v) clinical trials of retinoids and the limitations of retinoid use, (vi) novel systems of retinoid delivery, and (vii) components of retinoid signalling pathways as potential novel therapeutic targets.

Keywords: bladder cancer; chemoprevention; clinical trials; delivery systems; experimental bladder cancer models; novel targets; retinoic acid signalling; retinoids; treatment; vitamin A.

Publication types

  • Review

MeSH terms

  • Animals
  • Anticarcinogenic Agents / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis
  • Cell Differentiation
  • Humans
  • Retinoids / metabolism*
  • Retinoids / pharmacology
  • Retinoids / therapeutic use
  • Signal Transduction
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / physiopathology
  • Urinary Bladder Neoplasms / prevention & control
  • Vitamin A / metabolism*
  • Vitamin A / pharmacology
  • Vitamin A / therapeutic use

Substances

  • Anticarcinogenic Agents
  • Antineoplastic Agents
  • Retinoids
  • Vitamin A