RAF265 inhibits the growth of advanced human melanoma tumors.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Yingjun SuAnn Richmond

Abstract

The purpose of this preclinical study was to determine the effectiveness of RAF265, a multikinase inhibitor, for treatment of human metastatic melanoma and to characterize traits associated with drug response. Advanced metastatic melanoma tumors from 34 patients were orthotopically implanted to nude mice. Tumors that grew in mice (17 of 34) were evaluated for response to RAF265 (40 mg/kg, every day) over 30 days. The relation between patient characteristics, gene mutation profile, global gene expression profile, and RAF265 effects on tumor growth, mitogen-activated protein/extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) phosphorylation, proliferation, and apoptosis markers was evaluated. Nine of the 17 tumors that successfully implanted (53%) were mutant BRAF (BRAF(V600E/K)), whereas eight of 17 (47%) tumors were BRAF wild type (BRAF(WT)). Tumor implants from 7 of 17 patients (41%) responded to RAF265 treatment with more than 50% reduction in tumor growth. Five of the 7 (71%) responders were BRAF(WT), of which 1 carried c-KIT(L576P) and another N-RAS(Q61R) mutation, while only 2 (29%) of the responding tumors were BRAF(V600E/K). Gene expression microarray data from nonimplanted tumors rev...Continue Reading

References

Jan 31, 2002·EMBO Reports·Sophie VasseurJuan Lucio Iovanna
Mar 30, 2004·Oncogene·Sandra PaveyNicholas K Hayward
Jun 23, 2004·Oncogene·Maria KarasaridesRichard Marais
Aug 3, 2004·Nature Medicine·Bert Vogelstein, Kenneth W Kinzler
Aug 25, 2004·Cancer Cell·Gergely SzakácsMichael M Gottesman
Aug 23, 2005·Nature Cell Biology·Honglai ZhangCun-Yu Wang
Nov 18, 2005·The New England Journal of Medicine·John A CurtinBoris C Bastian
Jul 19, 2006·Proceedings of the National Academy of Sciences of the United States of America·Martin MonteClaudio Schneider
Aug 2, 2006·British Journal of Cancer·T EisenM J Ratain
Oct 4, 2006·International Journal of Molecular Medicine·Wen G JiangOystein Fodstad
Jan 9, 2007·Human Reproduction·Morten F GjerstorffHenrik J Ditzel
May 23, 2007·Pigment Cell Research·Peter JohanssonNicholas Hayward
Jul 17, 2007·Current Opinion in Immunology·Jerry M Adams, Suzanne Cory
Aug 30, 2007·Apoptosis : an International Journal on Programmed Cell Death·Ainhoa MielgoUrsula Günthert
Oct 24, 2008·Journal of Medicinal Chemistry·Savithri RamurthyPaul A Renhowe
Oct 25, 2008·The Journal of Clinical Investigation·Mark S CraggClare L Scott
Jul 25, 2009·Nature Reviews. Drug Discovery·Pasi A JänneJeff Settleman
Dec 19, 2009·Neoplasia : an International Journal for Oncology Research·Chi-Hung HuangMuh-Hwa Yang
Jun 8, 2010·The New England Journal of Medicine·F Stephen HodiWalter J Urba
Jun 25, 2010·The Journal of Investigative Dermatology·Fred M KaplanAndrew E Aplin
Jul 27, 2010·Journal of Cellular Physiology·Carla E CanoJuan L Iovanna
Sep 8, 2010·The New England Journal of Medicine·Keith T FlahertyPaul B Chapman
Nov 26, 2010·Nature·Cory M JohannessenLevi A Garraway
Mar 11, 2011·Neoplasia : an International Journal for Oncology Research·Jeffrey R TsengSanjiv S Gambhir
Jun 7, 2011·The New England Journal of Medicine·Paul B ChapmanUNKNOWN BRIM-3 Study Group
Jun 15, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Keith T Flaherty, David E Fisher
Nov 9, 2011·Disease Models & Mechanisms·Nihed Draoui, Olivier Feron

❮ Previous
Next ❯

Citations

Apr 16, 2013·Cancer Metastasis Reviews·Yabin ChengGang Li
Oct 13, 2012·Nature Reviews. Drug Discovery·Gideon BollagPeter Hirth
Sep 20, 2007·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·Jiehua LinShusheng Zhang
Dec 20, 2012·Drug Design, Development and Therapy·Alexander M MenziesRajmohan Murali
Dec 12, 2013·Pharmacology & Therapeutics·Carolina Hertzman Johansson, Suzanne Egyhazi Brage
Nov 20, 2014·Future Medicinal Chemistry·Chao DingYuyang Jiang
Jun 23, 2012·Current Oncology Reports·Janice M Mehnert, Harriet M Kluger
Jan 31, 2013·Expert Opinion on Therapeutic Targets·Asami Takashima, Douglas V Faller
May 7, 2013·Expert Opinion on Investigational Drugs·Samra TurajlicJames Larkin
Nov 1, 2015·American Journal of Clinical Dermatology·Hugo Akabane, Ryan J Sullivan
Jun 2, 2014·Hematology/oncology Clinics of North America·Ryan J Sullivan, David E Fisher
Jan 7, 2014·Critical Reviews in Oncology/hematology·M A RahmanA K-Y Lam
Jul 31, 2013·IUBMB Life·Ao-Xue Wang, Xiao-Yi Qi
Mar 23, 2015·Current Treatment Options in Oncology·Douglas B Johnson, Igor Puzanov
Sep 10, 2014·Cell Reports·Simona LambaAlberto Bardelli
Sep 3, 2014·British Journal of Cancer·I V FedorenkoK S M Smalley
May 7, 2016·Scientific Reports·King Tuo YipRaphael Stoll
May 11, 2016·The Journal of Investigative Dermatology·Christian PoschSusana Ortiz-Urda
Jan 1, 2016·Journal of the National Cancer Institute·Anna E VilgelmAnn Richmond
Sep 7, 2019·Nature Communications·Shingo KomuraYasuhiro Yamada
Mar 1, 2016·Melanoma Management·Benjamin Y KongAlexander M Menzies
Jun 21, 2014·Melanoma Research·Inna V FedorenkoKeiran S M Smalley
Apr 3, 2019·International Journal of Molecular Sciences·Paola SavoiaOttavio Cremona
May 21, 2013·Molecular Cancer Therapeutics·Arthur Kwok Leung CheungMaria Li Lung
Apr 18, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Justine V Cohen, Ryan J Sullivan
Sep 10, 2015·Molecular Cancer Therapeutics·Steven R WhittakerLevi A Garraway
Sep 24, 2021·The Journal of Clinical Investigation·Raie T BekeleKent W Mouw

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

© 2022 Meta ULC. All rights reserved