Page 146 - Read Online

Kumar et al. Cancer Drug Resist 2019;2:161-77 Cancer
DOI: 10.20517/cdr.2018.27 Drug Resistance

Review Open Access

Emerging targets in cancer drug resistance

Shashank Kumar , Prem Prakash Kushwaha , Sanjay Gupta 2,3,4,5,6
1
1
1 School of Basic and Applied Sciences, Department of Biochemistry and Microbial Sciences, Central University of Punjab,
Bathinda 151001, India.
2 Department of Urology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
3 The Urology Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio 44106, USA.
4 Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106, USA.
5 Divison of General Medical Sciences, Case Comprehensive Cancer Center, Cleveland, Ohio 44106, USA.
6 Department of Urology, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio 44106, USA.

Correspondence to: Prof. Sanjay Gupta, The James and Eilleen Dicke Laboratory, Department of Urology, Case Western Reserve
University, 2109 Adelbert Road, Wood Research Tower-RTG01 Cleveland, Ohio 44106, USA. E-mail: sanjay.gupta@case.edu

How to cite this article: Kumar S, Kushwaha PP, Gupta S. Emerging targets in cancer drug resistance. Cancer Drug Resist
2019;2:161-77. http://dx.doi.org/10.20517/cdr.2018.27
Received: 27 Nov 2018 First Decision: 19 Feb 2019 Revised: 8 Mar 2019 Accepted: 14 Mar 2019 Published: 19 Jun 2019

Science Editor: Enrico Mini Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Drug resistance is a complex phenomenon that frequently develops as a failure to chemotherapy during cancer
treatment. Malignant cells increasingly generate resistance to various chemotherapeutic drugs through distinct
mechanisms and pathways. Understanding the molecular mechanisms involved in drug resistance remains an important
area of research for identification of precise targets and drug discovery to improve therapeutic outcomes. This review
highlights the role of some recent emerging targets and pathways which play critical role in driving drug resistance.

Keywords: Drug resistance, transforming growth factor-β, Keap1-Nrf2, PI3K-Akt, FOXO transcription factors, focal
adhesion kinases, annexins, MIEN1, gene splicing, sphingolipids, microRNA

INTRODUCTION
Drug resistance during cancer treatment frequently originates with the failure of chemotherapy. The
term “chemotherapy” was first introduced 70 years back by Goodman and co-workers for the treatment
[1]
of leukemia and lymphosarcoma at the end of the II World war . Since then chemotherapy remains a
mainstay treatment modality in cancer management. A large number of targets and treatment approaches
to cancer have recently emerged, however pertinent resistance and severe side-effects remains a major
clinical problem. A large patient inter-individual variability in their pharmacokinetics and inconsistent
[2]
antitumor effects has been observed for most anticancer drugs . However, most patients do not respond
© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

www.cdrjournal.com