Overcoming Therapy Resistance in Colon Cancer by Drug Repurposing

Abstract

Colorectal cancer (CRC) is the third most common cancer in the world. Despite improvement in standardized screening methods and the development of promising therapies, the 5-year survival rates are as low as 10% in the metastatic setting. The increasing life expectancy of the general population, higher rates of obesity, poor diet, and comorbidities contribute to the increasing trends in incidence. Drug repurposing offers an affordable solution to achieve new indications for previously approved drugs that could play a protagonist or adjuvant role in the treatment of CRC with the advantage of treating underlying comorbidities and decreasing chemotherapy toxicity. This review elaborates on the current data that supports drug repurposing as a feasible option for patients with CRC with a focus on the evidence and mechanism of action promising repurposed candidates that are widely used, including but not limited to anti-malarial, anti-helminthic, anti-inflammatory, anti-hypertensive, anti-hyperlipidemic, and anti-diabetic agents.

Keywords: colorectal cancer; drug repurposing; in silico drug screens; therapy resistance.

Figure 1

Mode of action of candidate repurposed drugs being tested in clinical trials for patients with CRC. HDAC: Histone Deacetylase; TNIK: TRAF2 And NCK Interacting Kinase; COX: Cyclo-oxygenase; mTOR: mammalian Target of Rapamycin. Adapted from “Round-Cell Background”, by BioRender.com (2022). Retrieved from https://app.biorender.com/biorender-templates accessed on 15 April 2022.