Williams Cancer Institute

Pentoxifylline an FDA Approved

Pentoxifylline an FDA Approved Drug for Vascular Disease That May Boost Immunotherapy

Pentoxifylline, sold under the brand name Trental is typically used for vascular disease to increase blood flow due to its effect in reducing blood viscosity.  However, there is a gene called c-Rel that is important to maintain the function of regulatory cells such as Tregs and MDSC.  As I have discussed, the immune system has two sides, one that is regulatory, which has been tricked by cancer to protect it.  There is the other side that can attack cancer.

Our goal is to tip the balance in favor of attacking cancer.   In a study published by Grinberg-Bleyer, et al in Cell, Sept 7, 2017, titled “NF-kB c-Rel Is Crucial for the Regulatory T Cell Immune Checkpoint in Cancer” they describe how blocking c-Rel can reduce the regulatory function of Tregs.  In addition, Li, et al published in Nature Cancer, May 18, 2020, an article titled “c-Rel is a Myeloid Checkpoint for Cancer Immunotherapy” which discusses MDSC.

These two articles are describing how c-Rel is key to two of the main groups of immune cells that can inhibit an anti-cancer immune response.  In turn, blocking c-Rel was demonstrated in animals to enhance standard immunotherapy, such as PD-1 inhibitors.  Blocking both c-Rel and PD-1 together was better than either alone.  The study by Grinberg-Bleyer showed that Pentoxifylline, a c-Rel inhibitor delayed tumor growth in the mouse model.  When administered with a PD-1 inhibitor, the effects of both were enhanced.  Though there are other c-Rel inhibitors in development, since Pentoxifylline is available and FDA approved, it may allow for off-label use which could improve the results of immunotherapy.

Reference: Samlaska, C. P. (1994). Pentoxifylline. Journal of the American Academy of Dermatology,, 603-621. Obtenido de https://doi.org/10.1016/s0190-9622(94)70069-9

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