Cichowski Lab

Brigham & Women's Hospital | Harvard Medical School

Therapeutic development

There has been significant progress in developing targeted therapies for cancers driven by mutations in genes that encode enzymes (e.g. kinases). However, developing effective therapies for cancers that are driven by mutations that do not directly affect a targetable protein represents a major challenge in cancer research. Ras-driven cancers represent an important example of this challenge. We have been taking innovative approaches to develop novel combination therapies for Ras driven tumors and have recently made important advances in developing potential therapies for nervous system malignancies and lung cancer.


USP9X mediates an acute adaptive response to MAPK suppression in pancreatic cancer but creates multiple actionable therapeutic vulnerabilities

Naiara Perurena, Rebecca Lock, Rachel A. Davis, Srivatsan Raghavan, Natalie F. Pilla, Raymond Ng, Patrick Loi, Caroline J. Guild, Abigail L. Miller, Ewa Sicinska, James M. Cleary, Douglas A. Rubinson, Brian M. Wolpin, Nathanael S. Gray, Sandro Santagata, William C. Hahn, Jennifer P. Morton, Owen J. Sansom, Andrew J. Aguirre, Karen Cichowski

Cell Reports Medicine, 2023 Apr

Combating castration-resistant prostate cancer by co-targeting the epigenetic regulators EZH2 and HDAC

Amy E. Schade, Ryan Kuzmickas, Carrie L. Rodriguez, Kaia Mattioli, Miriam Enos, Alycia Gardner, Karen Cichowski

PLOS Biology, vol. 21, Public Library of Science, 2023 Apr, pp. 1-21

MAPK Pathway Suppression Unmasks Latent DNA Repair Defects and Confers a Chemical Synthetic Vulnerability in BRAF-, NRAS-, and NF1-Mutant Melanomas

Ophélia Maertens, Ryan Kuzmickas, Haley E. Manchester, Chloe E. Emerson, Alessandra G. Gavin, Caroline J. Guild, Terence C. Wong, Thomas De Raedt, Christian Bowman-Colin, Elodie Hatchi, Levi A. Garraway, Keith T. Flaherty, Shailja Pathania, Stephen J. Elledge, Karen Cichowski

Cancer Discovery, vol. 9, 2019 Apr, pp. 526-545

mTOR and HDAC Inhibitors Converge on the TXNIP/Thioredoxin Pathway to Cause Catastrophic Oxidative Stress and Regression of RAS-Driven Tumors

Clare F. Malone, Chloe Emerson, Rachel Ingraham, William Barbosa, Stephanie Guerra, Haejin Yoon, Lin L. Liu, Franziska Michor, Marcia Haigis, Kay F. Macleod, Ophélia Maertens, Karen Cichowski

Cancer Discovery, vol. 7, 2017 Dec, pp. 1450-1463

A Collaborative Model for Accelerating the Discovery and Translation of Cancer Therapies

Ophélia Maertens, Mila E. McCurrach, Benjamin S. Braun, Thomas De Raedt, Inbal Epstein, Tannie Q. Huang, Jennifer O. Lauchle, Hyerim Lee, Jianqiang Wu, Timothy P. Cripe, D. Wade Clapp, Nancy Ratner, Kevin Shannon, Karen Cichowski

Cancer Research, vol. 77, 2017 Oct, pp. 5706-5711

Cotargeting MNK and MEK kinases induces the regression of NF1-mutant cancers

Rebecca Lock, Rachel Ingraham, Ophélia Maertens, Abigail L. Miller, Nelly Weledji, Eric Legius, Bruce M. Konicek, Sau-Chi B. Yan, Jeremy R. Graff, Karen Cichowski

The Journal of Clinical Investigation, vol. 126, The American Society for Clinical Investigation, 2016 Jun, pp. 2181-2190


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