Abstract

Due to the high resistance that cancer has shown to conventional therapies, it is difficult to treat this disease, particularly in advanced stages. In recent decades, treatments have been improved, being more specific according to the characteristics of the tumor, becoming more effective, less toxic, and invasive. Cancer can be treated by the combination of surgery, radiation therapy, and/or drug administration, but therapies based on anticancer drugs are the main cancer treatment. Cancer drug development requires long-time preclinical and clinical studies and is not cost-effective. Drug repurposing is an alternative for cancer therapies development since it is faster, safer, easier, cheaper, and repurposed drugs do not have serious side effects. However, cancer is a complex, heterogeneous, and highly dynamic disease with multiple evolving molecular constituents. This tumor heterogeneity causes several resistance mechanisms in cancer therapies, mainly the target mutation. The CRISPR-dCas9-based artificial transcription factors (ATFs) could be used in cancer therapy due to their possibility to manipulate DNA to modify target genes, activate tumor suppressor genes, silence oncogenes, and tumor resistance mechanisms for targeted therapy. In addition, drug repurposing combined with the use of CRISPR-dCas9-based ATFs could be an alternative cancer treatment to reduce cancer mortality. The aim of this review is to describe the potential of the repurposed drugs combined with CRISPR-dCas9-based ATFs to improve the efficacy of cancer treatment, discussing the possible advantages and disadvantages.

Highlights

  • Cancer represents one of the most important health challenges in the world

  • CRISPR-dCas9-Based artificial transcription factors (ATFs) for Cancer Treatment therapy applied; anticancer drug-based therapies are the main treatment used in different tumor types [2]

  • Pregenomic era drugs are targeted against a tumor phenotype, whereas genomic era drugs are developed after the target is identified by using molecular techniques that consider intratumoral genetic heterogeneity [1, 3, 4]

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Summary

Introduction

Cancer represents one of the most important health challenges in the world It can be treated by the combination of surgery, radiation therapy, and/or drug administration. Some repurposed drugs have demonstrated antitumor efficacy by inducing cancer cell death or suppressing various genes related to cancer [12]. There are different mechanisms by which the repurposed drugs cause antitumor effects, it is important to study mechanisms that regulate gene expression related to proliferation and cell death to improve the cancer treatment efficacy and avoid drug resistance. The possibility to combine pregenomic era drugs and molecular tools could increase tumor cell killing and reduce the likelihood of drug resistance [1]

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