Phase I Trial of Regorafenib, Hydroxychloroquine, and Entinostat in Metastatic Colorectal Cancer | Zendy

Thomas B. Karasic | Zendy; Timothy J. Brown | Zendy; Charles Schneider | Zendy; Ursina Teitelbaum | Zendy; Kim A. Reiss | Zendy; Tara C. Mitchell | Zendy; Ryan Massa | Zendy; Mark H. O’Hara | Zendy; Lisa Dicicco | Zendy; Luis Garcia-Marcano | Zendy; Ravi K. Amaravadi | Zendy; Peter J. O’Dwyer | Zendy

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Phase I Trial of Regorafenib, Hydroxychloroquine, and Entinostat in Metastatic Colorectal Cancer

Author(s) -

Thomas B. Karasic,

Timothy J. Brown,

Charles Schneider,

Ursina Teitelbaum,

Kim A. Reiss,

Tara C. Mitchell,

Ryan Massa,

Mark H. O’Hara,

Lisa Dicicco,

Luis Garcia-Marcano,

Ravi K. Amaravadi,

Peter J. O’Dwyer

Publication year - 2022

Publication title -

the oncologist

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.176

H-Index - 164

eISSN - 1549-490X

pISSN - 1083-7159

DOI - 10.1093/oncolo/oyac078

Subject(s) - medicine , regorafenib , colorectal cancer , oncology , phases of clinical research , autophagy , hydroxychloroquine , cancer , pharmacology , toxicity , apoptosis , biochemistry , chemistry , disease , covid-19 , infectious disease (medical specialty)

The antiangiogenic tyrosine kinase inhibitor regorafenib provides a survival benefit in patients with previously treated metastatic colorectal cancer (CRC). Antiangiogenic therapy causes hypoxic stress within tumor cells, which activates autophagy as a survival mechanism. The histone deacetylase inhibitor (HDAC) entinostat increases dependence on autophagy through epigenetic mechanisms. Hydroxychloroquine (HCQ) blocks autophagy by blunting lysosomal acidification. We hypothesized that HCQ and entinostat would be tolerable with regorafenib and potentiate the antitumor response.

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