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PHIP as a therapeutic target for driver-negative subtypes of melanoma, breast, and lung cancer [Medical Sciences]

The development of targeted therapies represents a major advance in cancer therapy, with its most prominent examples including agents targeting HER2 in breast cancer, EGFR and ALK in lung cancer, and BRAF in melanoma. However, a key challenge confronting such precision medicine approaches concerns the presence of subtypes of each of these three common, lethal solid tumors that lack identified molecular drivers, and are thus not amenable to targeted therapies. Our studies identify a role for pleckstrin homology domain-interacting protein (PHIP) in promoting the progression of “driver-negative” subtypes of these common solid tumors. In addition, they demonstrate a physical interaction between PHIP and an activating histone modification, thereby identifying PHIP as a rational target for the therapy of these solid tumor subtypes.

Authors:   David de Semir; Vladimir Bezrookove; Mehdi Nosrati; Altaf A. Dar; Clayton Wu; Julia Shen; Christopher Rieken; Meenakshi Venkatasubramanian; James R. Miller; Pierre-Yves Desprez; Sean McAllister; Liliana Soroceanu; Robert J. Debs; Nathan Salomonis; Dirk Schadendorf; James E. Cleaver; Mohammed Kashani-Sabet
Journal:   Proceedings of the National Academy of Sciences current issue
Volume:   115
edition:   25
Year:   2018
Pages:   E5766
DOI:   10.1073/pnas.1804779115
Publication date:   19-Jun-2018
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