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Akademický článek

Combined inhibition of KRASG12C and mTORC1 kinase is synergistic in non-small cell lung cancer

Publikováno v: Nature Communications, Vol 15, Iss 1, Pp 1-15 (2024)

Abstract Current KRASG12C (OFF) inhibitors that target inactive GDP-bound KRASG12C cause responses in less than half of patients and these responses are not durable. A class of RASG12C (ON) inhibitors that targets active GTP-bound KRASG12C blocks ERK

Externí odkaz: https://doaj.org/article/7ad6de68f66945a2a3cb9c50ceaaf9b5

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Akademický článek

HER2 + breast cancers evade anti-HER2 therapy via a switch in driver pathway

Autor: Alison E. Smith, Emanuela Ferraro, Anton Safonov, Cristina Bernado Morales, Enrique J. Arenas Lahuerta, Qing Li, Amanda Kulick, Dara Ross, David B. Solit, Elisa de Stanchina, Jorge Reis-Filho, Neal Rosen, Joaquín Arribas, Pedram Razavi, Sarat Chandarlapaty

Publikováno v: Nature Communications, Vol 12, Iss 1, Pp 1-10 (2021)

Resistance to HER2 inhibition in HER2- amplified breast cancer is common in the metastatic setting and the underlying molecular mechanisms remain unknown. Here, the authors, perform genomic profiling of 733 HER2-amplified breast cancers and propose g

Externí odkaz: https://doaj.org/article/0069fe3f63d440449928bce36543115c

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Akademický článek

Defining the therapeutic selective dependencies for distinct subtypes of PI3K pathway-altered prostate cancers

Autor: Ninghui Mao, Zeda Zhang, Young Sun Lee, Danielle Choi, Aura Agudelo Rivera, Dan Li, Cindy Lee, Samuel Haywood, Xiaoping Chen, Qing Chang, Guotai Xu, Hsuan-An Chen, Elisa de Stanchina, Charles Sawyers, Neal Rosen, Andrew C. Hsieh, Yu Chen, Brett S. Carver

Publikováno v: Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021)

Understanding the mechanisms driving PI3K isoform dependency in prostate cancer can help the design of future clinical trials. Here, the authors show that gain-of-function mutations in PIK3CA or PIK3CB can confer PI3K p110 isoform dependency and that

Externí odkaz: https://doaj.org/article/907e2e85e15748fa85c06a824495c169

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Akademický článek

Anti-tumor effects of an ID antagonist with no observed acquired resistance

Publikováno v: npj Breast Cancer, Vol 7, Iss 1, Pp 1-17 (2021)

Abstract ID proteins are helix-loop-helix (HLH) transcriptional regulators frequently overexpressed in cancer. ID proteins inhibit basic-HLH transcription factors often blocking differentiation and sustaining proliferation. A small-molecule, AGX51, t

Externí odkaz: https://doaj.org/article/fcc94ce778e043e9991e8da7d30777e4

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Akademický článek

Mutant-selective degradation by BRAF-targeting PROTACs

Autor: Shanique Alabi, Saul Jaime-Figueroa, Zhan Yao, Yijun Gao, John Hines, Kusal T. G. Samarasinghe, Lea Vogt, Neal Rosen, Craig M. Crews

Publikováno v: Nature Communications, Vol 12, Iss 1, Pp 1-11 (2021)

Hundreds of BRAF mutations have been identified in patients with cancer but currently approved drugs only target BRAF V600 mutants. Here, the authors develop a vemurafenib-based PROTAC that induces degradation of all classes of BRAF mutants without a

Externí odkaz: https://doaj.org/article/c199e2f0eb92437a873d93ab5b38d197

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Akademický článek

RAF dimer inhibition enhances the antitumor activity of MEK inhibitors in K‐RAS mutant tumors

Publikováno v: Molecular Oncology, Vol 14, Iss 8, Pp 1833-1849 (2020)

The mutation of K‐RAS represents one of the most frequent genetic alterations in cancer. Targeting of downstream effectors of RAS, including of MEK and ERK, has limited clinical success in cancer patients with K‐RAS mutations. The reduced sensiti

Externí odkaz: https://doaj.org/article/3c9d127250f544f0b8e196531da074da

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Akademický článek

Phase 1 Clinical Trial of Trametinib and Ponatinib in Patients With NSCLC Harboring KRAS Mutations

Autor: Kathryn C. Arbour, MD, Eusebio Manchado, PhD, Matthew J. Bott, MD, Linda Ahn, NP, Yosef Tobi, BA, Andy Ai Ni, Helena A. Yu, MD, Alyssa Shannon, BA, Marc Ladanyi, MD, Victoria Perron, BS, Michelle S. Ginsberg, MD, Amanda Johnson, BA, Andrei Holodny, MD, Mark G. Kris, MD, Charles M. Rudin, MD, PhD, Piro Lito, MD, PhD, Neal Rosen, MD, PhD, Scott Lowe, PhD, Gregory J. Riely, MD, PhD

Publikováno v: JTO Clinical and Research Reports, Vol 3, Iss 1, Pp 100256- (2022)

Introduction: Somatic KRAS mutations occur in 25% of patients with NSCLC. Treatment with MEK inhibitor monotherapy has not been successful in clinical trials to date. Compensatory activation of FGFR1 was identified as a mechanism of trametinib resist

Externí odkaz: https://doaj.org/article/08ab67b4ab914fc8921cb36a60feebfe

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