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Drug repurposing to overcome resistance to various therapies for colorectal cancer

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Abstract

Emergence of novel treatment modalities provides effective therapeutic options, apart from conventional cytotoxic chemotherapy, to fight against colorectal cancer. Unfortunately, drug resistance remains a huge challenge in clinics, leading to invariable occurrence of disease progression after treatment initiation. While novel drug development is unfavorable in terms of time frame and costs, drug repurposing is one of the promising strategies to combat resistance. This approach refers to the application of clinically available drugs to treat a different disease. With the well-established safety profile and optimal dosing of these approved drugs, their combination with current cancer therapy is suggested to provide an economical, safe and efficacious approach to overcome drug resistance and prolong patient survival. Here, we review both preclinical and clinical efficacy, as well as cellular mechanisms, of some extensively studied repurposed drugs, including non-steroidal anti-inflammatory drugs, statins, metformin, chloroquine, disulfiram, niclosamide, zoledronic acid and angiotensin receptor blockers. The three major treatment modalities in the management of colorectal cancer, namely classical cytotoxic chemotherapy, molecular targeted therapy and immunotherapy, are covered in this review.

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Abbreviations

ARB:

Angiotensin II receptor blockers

CAF:

Cancer-associated fibroblast

CXCL-12:

Chemokine (C-X-C motif) ligand 12

DC:

Dendritic cells

gp70:

An envelope protein of an endogenous ecotropic murine leukemia virus

IL-6:

Interleukin 6

IFN-γ:

Interferon-gamma

MDSC:

Myeloid-derived suppressing cells

NK cells:

Natural killer cells

NOS-2:

Nitric oxide synthase 2

TAM:

Tumor-associated macrophages

TEM:

Effector memory T cells

Treg:

Regulatory T cells

VEGF:

Vascular endothelial growth factor

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Acknowledgements

The authors’ team was supported by the Health and Medical Research Fund [Food and Health Bureau, Hong Kong SAR, grant number 03140276] and a research grant from the Medicine Panel of the Chinese University of Hong Kong [Direct Grant for Research 4054371].

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    Winnie Fong & Kenneth K. W. To

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Fong, W., To, K.K.W. Drug repurposing to overcome resistance to various therapies for colorectal cancer. Cell. Mol. Life Sci. 76, 3383–3406 (2019). https://doi.org/10.1007/s00018-019-03134-0

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