Stuart A. Aaronson

Spatial modulation of RAF by RAF/MEK glue enables full-dose combination with pan-RAF inhibitor and potent RAS-mutant tumor-selective MAPK and growth inhibition

Ana Orive‐Ramos, Bijaya Gaire, Christos Adamopoulos, Beau Baars et autres

Abstract The clinical benefit of MAPK-targeted therapies depends on greater pathway inhibition in tumors than normal tissues. Although pan-RAF inhibitors are active in RAS-mutant cancers, combining them with MEK inhibitors requires dose reductions due to toxicity, limiting efficacy. We show the toxicity …

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Figure S5 from RAS Mutation–Specific Responses to Paralog- and State-Selective RAS Inhibitors

Beau Baars, Ana Orive-Ramos, Matthew J. Emmett, Bijaya Gaire et autres

Sensitivity to any single RAS-targeted inhibitor is restricted to the subset of RAS(MUT)-specific inhibitor-sensitive tumors

Figure S1 from RAS Mutation–Specific Responses to Paralog- and State-Selective RAS Inhibitors

Beau Baars, Ana Orive-Ramos, Matthew J. Emmett, Bijaya Gaire et autres

Chemical structures of compounds used in this study

Supplementary Data Legends from RAS Mutation–Specific Responses to Paralog- and State-Selective RAS Inhibitors

Beau Baars, Ana Orive-Ramos, Matthew J. Emmett, Bijaya Gaire et autres

Supplementary Data Legends

Figure S4 from RAS Mutation–Specific Responses to Paralog- and State-Selective RAS Inhibitors

Beau Baars, Ana Orive-Ramos, Matthew J. Emmett, Bijaya Gaire et autres

RAS(Q61R/K) cells are insensitive to combined SHP2i+MEKi treatment due to feedback activation of RAS(Q61R/K) and induction of a SHP2 conformation with reduced binding to SHP2i

Data from RAS Mutation–Specific Responses to Paralog- and State-Selective RAS Inhibitors

Beau Baars, Ana Orive-Ramos, Matthew J. Emmett, Bijaya Gaire et autres

Abstract A high therapeutic index, defined as potent inhibition of oncogenic signaling in tumor cells with minimal effects on normal cells, is critical for effective cancer therapies. Recent advances have introduced diverse RAS-targeting inhibitors, including mutant-specific inhibitors such as KRAS G12C and …

Figure S2 from RAS Mutation–Specific Responses to Paralog- and State-Selective RAS Inhibitors

Beau Baars, Ana Orive-Ramos, Matthew J. Emmett, Bijaya Gaire et autres

KRAS(G12X)-expressing cells exhibit differential sensitivity to panRAS- GEF(OFF)i

Figure S3 from RAS Mutation–Specific Responses to Paralog- and State-Selective RAS Inhibitors

Beau Baars, Ana Orive-Ramos, Matthew J. Emmett, Bijaya Gaire et autres

KRAS(G13D) cells are insensitive to next generation SHP2i and SOS1i

Retraction Note: ROCK1 mechano-signaling dependency of human malignancies driven by TEAD/YAP activation

Davide Esposito, Ila Pant, Yao Shen, Rui Fang Qiao et autres

3. Fig 1f p53 DNA contact mutant cells - HCC193-Ctr and Fig 2I p53 DNA contact mutant cells - HCC193-DMSO appear similar.

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RAS Mutation–Specific Responses to Paralog- and State-Selective RAS Inhibitors

Beau Baars, Ana Orive‐Ramos, Matthew J. Emmett, Bijaya Gaire et autres

A high therapeutic index, defined as potent inhibition of oncogenic signaling in tumor cells with minimal effects on normal cells, is critical for effective cancer therapies. Recent advances have introduced diverse RAS-targeting inhibitors, including mutant-specific inhibitors such as KRAS G12C and KRAS …

us, gr (code pays fourni par la source)

Prolonging lung cancer response to EGFR inhibition by targeting the selective advantage of resistant cells

Lisa J. Brunet, David Alexandre, Ji‐Young Lee, Maria del Mar Blanquer-Rosselló et autres

Non-small cell lung cancers (NSCLCs) treated with tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) almost invariably relapse in the long term, due to the emergence of subpopulations of resistant cells. Through a DNA barcoding approach, we show that …

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Abstract LB294: Mechanism of tumor-selective inhibition of dimeric RAF by a Type 1 RAF inhibitor

Mathieu Desaunay, Tara L. Peters, Beau Baars, Bijaya Gaire et autres

Abstract Over a third of human tumors are driven by deregulated RAS/MAPK signaling, frequently by mutations in RAS or BRAF. First generation RAF inhibitors bind in the Type 1.5 mode (αC-OUT/DFG-IN) and are effective in inhibiting monomeric BRAF(V600X), while inducing paradoxical RAF …

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