Hydroxychloroquine and the Power of Repurposed Medications in Cancer Immunotherapy

- Metformin: Known for treating type 2 diabetes, Metformin activates AMPK to improve T-cell function and reduce tumor-induced immunosuppression.
* Reference: Eikawa S, et al. 2015.

- Aspirin: Targets COX-2 to decrease prostaglandin E2 levels, reducing tumor-associated inflammation and boosting the effectiveness of immune checkpoint inhibitors.
* Reference: Zelenay S, et al. 2015.

- Statins (e.g., Simvastatin): These cholesterol-lowering drugs enhance T-cell activation and proliferation, potentially synergizing with immune checkpoint inhibitors by modifying the immune microenvironment.
* Reference: Grabowska J, et al. 2020.

- Hydroxychloroquine: This anti-malarial drug inhibits autophagy in cancer cells, enhancing antigen presentation and reducing immunosuppression in the tumor microenvironment.
* Reference: Piao S, Amaravadi RK. 2016.

- Propranolol: A beta-blocker that reduces stress-induced immunosuppression and enhances T-cell and NK cell activation.
* Reference: Montoya A, et al. 2019.

- Thalidomide: Boosts T-cell and NK cell functions while inhibiting angiogenesis, playing a crucial role in reducing tumor growth and improving immune responses.
* Reference: Bartlett JB, et al. 2004.

- Celecoxib: A COX-2 inhibitor that reduces PGE2 levels, decreasing tumor-associated inflammation and enhancing the efficacy of immune checkpoint inhibitors.
* Reference: Zhu J, et al. 2021.

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Supporting Evidence:

Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat Rev Cancer. 2004;4(4):314-322. doi:10.1038/nrc1323.

Eikawa S, Nishida M, Mizukami S, et al. Immune-mediated antitumor effect by type 2 diabetes drug, metformin. Proc Natl Acad Sci U S A. 2015;112(6):1809-1814. doi:10.1073/pnas.1417636112.

Grabowska J, Lopez-Venegas MA, Affandi AJ, et al. Statins Reprogram Tumor Immune Microenvironment via Inhibition of N-Glycosylation to Promote Therapeutic Efficacy of Immune Checkpoint Inhibitors. Sci Rep. 2020;10(1):2197. doi:10.1038/s41598-020-58983-1.

Montoya A, Varela-Ramirez A, Dickerson E, et al. The beta adrenergic receptor antagonist propranolol alters mitogenic and apoptotic signaling in late stage breast cancer. Biomed J. 2019;42(3):155-165. doi:10.1016/j.bj.2019.06.001.

Piao S, Amaravadi RK. Targeting the lysosome in cancer. Ann N Y Acad Sci. 2016;1371(1):45-54. doi:10.1111/nyas.13022.

Zelenay S, van der Veen AG, Böttcher JP, et al. Cyclooxygenase-Dependent Tumor Growth through Evasion of Immunity. Cell. 2015;162(6):1257-1270. doi:10.1016/j.cell.2015.08.015.

Zhu J, Sanidad KZ, Sukamtoh E, et al. The role of COX-2 inhibitors in immune checkpoint blockade therapy: Prospective combinations. Cancer Lett. 2021;502:134-150. doi:10.1016/j.canlet.2020.11.027.

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