4.7 Review

Molecular determinants as therapeutic targets in cancer chemotherapy: An update

Journal

PHARMACOLOGY & THERAPEUTICS
Volume 200, Issue -, Pages 85-109

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2019.04.011

Keywords

Tumor targeting; mitochondrial targets; endoplasmic reticulum targets; nuclear targets; lysosome targets; pattern recognition receptors

Funding

  1. Indian Council of Medical Research (ICMR), New Delhi, India

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It is well known that cancer cells are heterogeneous in nature and very distinct from their normal counterparts. Commonly these cancer cells possess different and complementary metabolic profile, microenvironment and adopting behaviors to generate more ATPs to fulfill the requirement of high energy that is further utilized in the production of proteins and other essentials required for cell survival, growth, and proliferation. These differences create many challenges in cancer treatments. On the contrary, such situations of metabolic differences between cancer and normal cells may be expected a promising strategy for treatment purpose. In this article, we focus on the molecular determinants of oncogene-specific sub-organelles such as potential metabolites of mitochondria (reactive oxygen species, apoptotic proteins, cytochrome c, caspase 9, caspase 3, etc.), endoplasmic reticulum (unfolded protein response, PKR-like ER kinase, C/EBP homologous protein, etc.), nucleus (nucleolar phosphoprotein, nuclear pore complex, nuclear localization signal), lysosome (microenvironment, etc.) and plasma membrane phospholipids, etc. that might be exploited for the targeted delivery of anti-cancer drugs for therapeutic benefits. This review will help to understand the various targets of subcellular organelles at molecular levels. In the future, this molecular level understanding may be combined with the genomic profile of cancer for the development of the molecularly guided or personalized therapeutics for complete eradication of cancer. (C) 2019 Elsevier Inc. All rights reserved.

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