Strategies for the drug discovery and development of taxane anticancer therapeutics

Expert Opin Drug Discov. 2022 Nov;17(11):1193-1207. doi: 10.1080/17460441.2022.2131766. Epub 2022 Oct 14.

Abstract

Introduction: Paclitaxel and docetaxel have been extensively used in the clinic over the past three decades. Although the patents of these first-generation taxanes have expired, their clinical applications, particularly new formulations and combination therapies, are under active investigations. Inspired by the notable success of Abraxane and Lipusu, new formulations have been extensively developed. In parallel, to overcome multidrug resistance (MDR) and to eradicate cancer stem cells, immense efforts have been made on the discovery and development of new-generation taxanes with improved potency and superior pharmacological properties.

Areas covered: This review covers (a) natural sources of advanced intermediates used for semi-synthesis of taxane API, (b) new formulations, (c) the major issues of FDA approved taxanes, (d) the design and development of next-generation taxanes, (e) new mechanisms of action, and (f) a variety of taxane-based drug delivery systems.

Expert opinion: As the highly potent next-generation taxanes can eradicate cancer stem cells and overcome MDR, the priority is to develop these compounds as an integral part of cancer therapy, especially for pancreatic, colon and prostate cancers which hardly respond to checkpoint inhibitors. In order to mitigate undesirable side effects, the exploration of effective nanoformulations and tumor-targeted drug delivery systems are essential.

Keywords: Paclitaxel; cancer; drug delivery system; nanoformulation; next-generation taxanes.

Publication types

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

MeSH terms

  • Antineoplastic Agents*
  • Bridged-Ring Compounds / pharmacology
  • Bridged-Ring Compounds / therapeutic use
  • Drug Discovery
  • Humans
  • Male
  • Prostatic Neoplasms* / drug therapy
  • Taxoids / pharmacology
  • Taxoids / therapeutic use

Substances

  • taxane
  • Taxoids
  • Bridged-Ring Compounds
  • Antineoplastic Agents