Reverse repurposing: Potential utility of cancer drugs in nonmalignant illnesses.

Growth and immune process dysregulation can result in both cancer and nonmalignant disease (hereditary or acquired, with and without predisposition to malignancy). Moreover, perhaps unexpectedly, many nonmalignant illnesses harbor genomic alterations indistinguishable from druggable oncogenic drivers. Therefore, targeted compounds used successfully to treat cancer may have therapeutic potential for nonmalignant conditions harboring the same target. MEK, PI3K/AKT/mTOR, fibroblast growth factor receptor (FGFR), and NRG1/ERBB pathway genes have all been implicated in both cancer and noncancerous conditions, and several cognate antagonists, as well as Bruton's tyrosine kinase inhibitors, JAK inhibitors, and CD20-directed antibodies, have established or theoretical therapeutic potential to bridge cancer and benign diseases. Intriguingly, pharmacologically tractable cancer drivers characterize a wide spectrum of disorders without malignant potential, including but not limited to Alzheimer's disease and a variety of other neurodegenerative conditions, rheumatoid arthritis, achondroplastic dwarfism, and endometriosis. Expanded repositioning of oncology agents in order to benefit benign but serious medical illnesses is warranted.
Competing Interests: Declaration of interests R.K. has received research funding from Boehringer Ingelheim, Debiopharm, Foundation Medicine, Genentech, Grifols, Guardant, Incyte, Konica Minolta, Medimmune, Merck Serono, Omniseq, Pfizer, Sequenom, Takeda, and TopAlliance and from the NCI as well as consultant and/or speaker fees and/or a position as an advisory board member/consultant for Actuate Therapeutics; AstraZeneca; Bicara Therapeutics, Inc.; Biological Dynamics; Caris; Datar Cancer Genetics; Daiichi; EISAI; EOM Pharmaceuticals; Iylon; LabCorp; Merck; NeoGenomics; Neomed; Pfizer; Precirix; Prosperdtx; Regeneron; Roche; TD2/Volastra; Turning Point Therapeutics; and X-Biotech. She also has an equity interest in CureMatch, Inc., and IDbyDNA; serves on the board of CureMatch and CureMetrix; and is a cofounder of CureMatch. S.K. serves as a consultant for Medpace, Foundation Medicine, NeoGenomics, and CureMatch. He receives speaker fees from Chugai, Roche/Genentech, and Bayer and serves on the advisory board for Pfizer. He has research funding from ACT Genomics, Sysmex, Konica Minolta, OmniSeq, Personalis, and Function Oncology.
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