Results 11 to 20 of about 81,917 (261)

RAF isoform selectivity of MEK inhibitors and rational design of a covalent ARAF-MEK inhibitor. [PDF]

Sci Adv
Abstract Aberrant activation of the RAS/RAF/MEK/ERK pathway is a frequent cause of cancer. Allosteric MEK inhibitors block this pathway by binding RAF-MEK complexes to prevent activation of MEK by RAF. However, how MEK inhibitor potency varies across the three RAF isoforms remains poorly understood.
Chakraborty S, Jiang J, Camallonga JV, Gazgalis D, Gero TW, Tavares MT, Dittemore G, Tkacik E, Beyett TS, Jang DM, Ha BH, Gottlieb FH, Levitz T, Metivier RJ, Schmoker AM, Scott DA, Jeon H, Jänne PA, Eck MJ.   +18 more
europepmc   +3 more sources

Emerging MEK inhibitors

Expert Opinion on Emerging Drugs, 2010
The Ras/Raf/MEK/ERK pathway is often activated by genetic alterations in upstream signaling molecules. Integral components of this pathway such as Ras and B-Raf are also activated by mutation. The Ras/Raf/MEK/ERK pathway has profound effects on proliferative, apoptotic and differentiation pathways.
J.A. McCubrey, L.S. Steelman, S.L. Abrams, W.H. Chappell, S. Russo, R. Ove, M. Milella, A. Tafuri, LUNGHI, Paolo, BONATI, Antonio, F. Stivala, F. Nicolettti, M. Libra, A.M. Martelli, G. Montalto, M. Cervello   +15 more
openaire   +6 more sources

BRAF Splice Variant Resistance to RAF Inhibitor Requires Enhanced MEK Association

Cell Reports, 2018
Summary: Expression of aberrantly spliced BRAF V600E isoforms (BRAF V600E ΔEx) mediates resistance in 13%–30% of melanoma patients progressing on RAF inhibitors. BRAF V600E ΔEx confers resistance, in part, through enhanced dimerization.
Michael J. Vido, Kaitlyn Le, Edward J. Hartsough, Andrew E. Aplin   +3 more
doaj   +1 more source

MEK inhibition suppresses B regulatory cells and augments anti-tumor immunity.

PLoS ONE, 2019
Mitogen-activated protein kinase (MAPK) kinase (MEK) is an integral component of the RAS pathway and a therapeutic target in RAS-driven cancers. Although tumor responses to MEK inhibition are rarely durable, MEK inhibitors have shown substantial activity
Mark Yarchoan, Aditya A Mohan, Lauren Dennison, Teena Vithayathil, Amanda Ruggieri, Gregory B Lesinski, Todd D Armstrong, Nilofer S Azad, Elizabeth M Jaffee   +8 more
doaj   +1 more source

Crosstalk between PI3 Kinase/PDK1/Akt/Rac1 and Ras/Raf/MEK/ERK Pathways Downstream PDGF Receptor

Cellular Physiology and Biochemistry, 2013
Background/Aims: Our earlier studies suggested crosstalk between IRS/PI3 kinase/PDK1/Akt/Rac1/ROCK and (Shc2/Grb2/SOS)/Ras/Raf/MEK/ERK pathways downstream PDGF-ββ receptor responsible for chemotaxis and proliferation of malignant mesothelioma cells.
Emma Tabe Eko Niba, Hisao Nagaya, Takeshi Kanno, Ayako Tsuchiya, Akinobu Gotoh, Chiharu Tabata, Kohzo Kuribayashi, Takashi Nakano, Tomoyuki Nishizaki   +8 more
doaj   +1 more source

Combined MEK/MDM2 inhibition demonstrates antitumor efficacy in TP53 wild-type thyroid and colorectal cancers with MAPK alterations

Scientific Reports, 2022
Most tumors with activating MAPK (mitogen-activated protein kinase) pathway alterations respond poorly to MEK inhibitors alone. Here, we evaluated combination therapy with MEK inhibitor selumetinib and MDM2 inhibitor KRT-232 in TP53 wild-type and MAPK ...
Seyed Pairawan, Argun Akcakanat, Scott Kopetz, Coya Tapia, Xiaofeng Zheng, Huiqin Chen, Min Jin Ha, Yasmeen Rizvi, Vijaykumar Holla, Jing Wang, Kurt W. Evans, Ming Zhao, Naifa Busaidy, Bingliang Fang, Jack A. Roth, Ecaterina Ileana Dumbrava, Funda Meric-Bernstam   +16 more
doaj   +1 more source

Combining MEK and SRC inhibitors for treatment of colorectal cancer demonstrate increased efficacy in vitro but not in vivo

PLoS ONE, 2023
Metastatic colorectal cancer (mCRC) is the second leading cause of cancer deaths in the United States. More than 50% of patients with mCRC harbor mutations of the oncogenic driver RAS (KRAS or NRAS).
Fan Fan, Susmita Ghosh, Reid Powell, Jason Roszik, Yongsun Park, Mary Sobieski, Alexey Sorokin, Clifford Stephan, Scott Kopetz, Lee M. Ellis, Rajat Bhattacharya   +10 more
doaj   +3 more sources

Cobimetinib- and vemurafenib-induced granulomatous dermatitis and erythema induratum: A case report

SAGE Open Medical Case Reports, 2019
Metastatic melanoma is an aggressive malignancy. Survival can be increased with the combination of BRAF and MEK inhibition. BRAF inhibitor-induced cutaneous toxicities can be attenuated with MEK inhibition.
Marco AJ Iafolla, Jennifer Ramsay, Judy Wismer, Elaine McWhirter   +3 more
doaj   +1 more source

Synthetic Lethal Interaction of SHOC2 Depletion with MEK Inhibition in RAS-Driven Cancers

Cell Reports, 2019
Summary: The mitogen-activated protein kinase (MAPK) pathway is a critical effector of oncogenic RAS signaling, and MAPK pathway inhibition may be an effective combination treatment strategy. We performed genome-scale loss-of-function CRISPR-Cas9 screens
Rita Sulahian, Jason J. Kwon, Katherine H. Walsh, Emma Pailler, Timothy L. Bosse, Maneesha Thaker, Diego Almanza, Joshua M. Dempster, Joshua Pan, Federica Piccioni, Nancy Dumont, Alfredo Gonzalez, Jonathan Rennhack, Behnam Nabet, John A. Bachman, Amy Goodale, Yenarae Lee, Mukta Bagul, Rosy Liao, Adrija Navarro, Tina L. Yuan, Raymond W.S. Ng, Srivatsan Raghavan, Nathanael S. Gray, Aviad Tsherniak, Francisca Vazquez, David E. Root, Ari J. Firestone, Jeff Settleman, William C. Hahn, Andrew J. Aguirre   +30 more
doaj   +1 more source

A CRISPR screen identifies MAPK7 as a target for combination with MEK inhibition in KRAS mutant NSCLC. [PDF]

PLoS ONE, 2018
Mutant KRAS represents one of the most frequently observed oncogenes in NSCLC, yet no therapies are approved for tumors that express activated KRAS variants. While there is strong rationale for the use of MEK inhibitors to treat tumors with activated RAS/
Nicholas Dompe, Christiaan Klijn, Sara A Watson, Katherine Leng, Jenna Port, Trinna Cuellar, Colin Watanabe, Benjamin Haley, Richard Neve, Marie Evangelista, David Stokoe   +10 more
doaj   +1 more source