Taxanes – The Backbone of Medical Oncology

Abstract

Drug development in oncology has witnessed a revolutionary growth from its humble beginning with nitrogen mustard in 1940 to immunotherapy in 1986 (Interferon alpha). The arsenal of cytotoxics is ever increasing, contributing to better survival outcomes and improved quality of life. Over the years, many cytotoxics have fallen out of favor too, due to its side effects and availability of drugs with better efficacy and toxicity profile. Taxane, a microtubule stabilizing agent extracted from the poisonous Yew tree, was discovered in 1964 and came into clinical use in 1992 with its approval for ovarian cancer. This group has grown into a cornerstone of many treatment protocols, spanning multiple tumor types. This review discusses in brief the salient features of cytotoxic agents in this drug group, its history, physico-chemical properties, mechanism of action, pharmacodynamics, and pharmacokinetics. Though the benefits of taxanes are well understood, there are unique problems associated with the use of taxanes and there is an expanding literature on taxane resistance. We briefly look at the resistance mechanisms. There have been significant efforts to circumvent the problems related to conventional taxanes, with an attempt at creating newer carrier molecules and adjunct drugs with taxanes, which is slowly gaining traction in clinical practice.

Biosynthesis of anticancer phytochemical compounds and their chemistry

“…Using bio-based nanoparticles such as chitosan helps increase the bioavailability of these drugs ( Ashrafizadeh et al, 2020 ). Many taxol analogs are developed, such as larotaxel dehydrate, paclitaxel polyglumex, cabazitaxel, ortataxel, and taxoperein, are under clinical trials ( Newman et al, 2008 ; Jose, 2020 ) ( Table 1 ). Phase III clinical trials for treating breast and pancreatic cancer are now being conducted with larotaxel, which features a cyclopropane ring in place of the C-7 hydroxyl group ( Newman, Cragg, and Kingston, 2008 ).…”