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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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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DOI: https://doi.org/10.1007/s00018-019-03134-0