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Topical 5-fluorouracil elicits regressions of BRAF inhibitor-induced cutaneous squamous cell carcinoma.

Authors:
Amaya Viros Robert Hayward Matthew Martin Sharona Yashar Clarissa C Yu Berta Sanchez-Laorden Alfonso Zambon Dan Niculescu-Duvaz Caroline Springer Roger S Lo Richard Marais

J Invest Dermatol 2013 Jan 16;133(1):274-6. Epub 2012 Aug 16.

Seccio Dermatologia, Departament de Medicina, Hospital Universitari Vall d’Hebron, Universitat Autonomade Barcelona, Spain.

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http://dx.doi.org/10.1038/jid.2012.268DOI Listing
January 2013

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LXH254, a Potent and Selective ARAF-Sparing Inhibitor of BRAF and CRAF for the Treatment of MAPK-Driven Tumors.

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Kelli-Ann Monaco Scott Delach Jing Yuan Yuji Mishina Paul Fordjour Emma Labrot Daniel McKay Ribo Guo Stacy Higgins Hui Qin Wang Jinsheng Liang Karen Bui John Green Peter Aspesi Jessi Ambrose Felipa Mapa Lesley Griner Mariela Jaskelioff John Fuller Kenneth Crawford Gwynn Pardee Stephania Widger Peter S Hammerman Jeffrey A Engelman Darrin D Stuart Vesselina G Cooke Giordano Caponigro

Clin Cancer Res 2020 Dec 22. Epub 2020 Dec 22.

Novartis Institutes for Biomedical Research, Cambridge, Massachusetts.

Purpose: Targeting RAF for antitumor therapy in RAS-mutant tumors holds promise. Herein, we describe in detail novel properties of the type II RAF inhibitor, LXH254.

Experimental Design: LXH254 was profiled in biochemical, , and assays, including examining the activities of the drug in a large panel of cancer-derived cell lines and a comprehensive set of models. Read More

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AZD0364 Is a Potent and Selective ERK1/2 Inhibitor That Enhances Antitumor Activity in -Mutant Tumor Models when Combined with the MEK Inhibitor, Selumetinib.

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Vikki Flemington Emma J Davies David Robinson Linda C Sandin Oona Delpuech Pei Zhang Lyndsey Hanson Paul Farrington Sigourney Bell Katarzyna Falenta Francis D Gibbons Nicola Lindsay Aaron Smith Joanne Wilson Karen Roberts Michael Tonge Philip Hopcroft Sophie E Willis Martine P Roudier Claire Rooney Elizabeth A Coker Patricia Jaaks Mathew J Garnett Stephen E Fawell Clifford D Jones Richard A Ward Iain Simpson Sabina C Cosulich J Elizabeth Pease Paul D Smith

Mol Cancer Ther 2021 02 3;20(2):238-249. Epub 2020 Dec 3.

Bioscience, Oncology R&D, AstraZeneca, Cambridge, England, United Kingdom.

The RAS-regulated RAF-MEK1/2-ERK1/2 (RAS/MAPK) signaling pathway is a major driver in oncogenesis and is frequently dysregulated in human cancers, primarily by mutations in or genes. The clinical benefit of inhibitors of this pathway as single agents has only been realized in -mutant melanoma, with limited effect of single-agent pathway inhibitors in -mutant tumors. Combined inhibition of multiple nodes within this pathway, such as MEK1/2 and ERK1/2, may be necessary to effectively suppress pathway signaling in -mutant tumors and achieve meaningful clinical benefit. Read More

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The Clinicopathological and Survival Profiles Comparison Across Primary Sites in Acral Melanoma.

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Xiaoting Wei Di Wu Hang Li Rui Zhang Yu Chen Hong Yao Zhihong Chi Xinan Sheng Chuanliang Cui Xue Bai Zhonghui Qi Ke Li Shijie Lan Lizhu Chen Rui Guo Xinyu Yao Lili Mao Bin Lian Yan Kong Jie Dai Bixia Tang Xieqiao Yan Xuan Wang Siming Li Li Zhou Charles M Balch Lu Si Jun Guo

Ann Surg Oncol 2020 Sep 6;27(9):3478-3485. Epub 2020 Apr 6.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Haidian District, Beijing, China.

Background: The clinicopathological and survival profiles across primary sites in acral melanoma (AM) are still controversial and unclear.

Methods: This is a multi-center retrospective study. Clinicopathological data of AM patients diagnosed between 1 January 2000 and 31 December 2017 from 6 large tertiary hospitals in China were extracted. Read More

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Bristol rheumatoid arthritis fatigue scale is valid in patients with psoriatic arthritis and is associated with overall severe disease and higher comorbidities.

Authors:
Muhammad Haroon Agnes Szentpetery Mohsin Ashraf Phil Gallagher Oliver FitzGerald

Clin Rheumatol 2020 Jun 18;39(6):1851-1858. Epub 2020 Jan 18.

Department of Rheumatology, St. Vincent's University Hospital, Dublin, Ireland.

Aims: To (1) determine the reliability and validity of the Bristol Rheumatoid Arthritis Fatigue scale (BRAF-NRS) in patients with psoriatic arthritis (PsA) and (2) examine possible clinical associations of worse fatigue in PsA.

Methods: Study phase 1: BRAF-NRS scale validation cohort. A consecutive cohort of 70 PsA patients was recruited to complete the 3-item BRAF-NRS and the 13-item Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaires, alongside disease activity assessment. Read More

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June 2020
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Destabilization of NOXA mRNA as a common resistance mechanism to targeted therapies.

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Nat Commun 2019 11 14;10(1):5157. Epub 2019 Nov 14.

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave, Boston, 02115, MA, USA.

Most targeted cancer therapies fail to achieve complete tumor regressions or attain durable remissions. To understand why these treatments fail to induce robust cytotoxic responses despite appropriately targeting oncogenic drivers, here we systematically interrogated the dependence of cancer cells on the BCL-2 family of apoptotic proteins after drug treatment. We observe that multiple targeted therapies, including BRAF or EGFR inhibitors, rapidly deplete the pro-apoptotic factor NOXA, thus creating a dependence on the anti-apoptotic protein MCL-1. Read More

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November 2019
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