Literature DB >> 23549875

Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer.

Erin M Coffee1, Anthony C Faber, Jatin Roper, Mark J Sinnamon, Gautam Goel, Lily Keung, Wei Vivian Wang, Loredana Vecchione, Veerle de Vriendt, Barbara J Weinstein, Roderick T Bronson, Sabine Tejpar, Ramnik J Xavier, Jeffrey A Engelman, Eric S Martin, Kenneth E Hung.   

Abstract

PURPOSE: BRAF(V600E) mutations are associated with poor clinical prognosis in colorectal cancer (CRC). Although selective BRAF inhibitors are effective for treatment of melanoma, comparable efforts in CRC have been disappointing. Here, we investigated potential mechanisms underlying this resistance to BRAF inhibitors in BRAF(V600E) CRC. EXPERIMENTAL
DESIGN: We examined phosphoinositide 3-kinase (PI3K)/mTOR signaling in BRAF(V600E) CRC cell lines after BRAF inhibition and cell viability and apoptosis after combined BRAF and PI3K/mTOR inhibition. We assessed the efficacy of in vivo combination treatment using a novel genetically engineered mouse model (GEMM) for BRAF(V600E) CRC.
RESULTS: Western blot analysis revealed sustained PI3K/mTOR signaling upon BRAF inhibition. Our BRAF(V600E) GEMM presented with sessile serrated adenomas/polyps, as seen in humans. Combination treatment in vivo resulted in induction of apoptosis and tumor regression.
CONCLUSIONS: We have established a novel GEMM to interrogate BRAF(V600E) CRC biology and identify more efficacious treatment strategies. Combination BRAF and PI3K/mTOR inhibitor treatment should be explored in clinical trials. ©2013 AACR

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Year:  2013        PMID： 23549875      PMCID： PMC3815598          DOI： 10.1158/1078-0432.CCR-12-2556

Source DB:  PubMed          Journal:  Clin Cancer Res        ISSN： 1078-0432            Impact factor:   12.531


  47 in total

1.  Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR.

Authors:  Anirudh Prahallad; Chong Sun; Sidong Huang; Federica Di Nicolantonio; Ramon Salazar; Davide Zecchin; Roderick L Beijersbergen; Alberto Bardelli; René Bernards
Journal:  Nature       Date:  2012-01-26       Impact factor: 49.962

2.  EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib.

Authors:  Ryan B Corcoran; Hiromichi Ebi; Alexa B Turke; Erin M Coffee; Michiya Nishino; Alexandria P Cogdill; Ronald D Brown; Patricia Della Pelle; Dora Dias-Santagata; Kenneth E Hung; Keith T Flaherty; Adriano Piris; Jennifer A Wargo; Jeffrey Settleman; Mari Mino-Kenudson; Jeffrey A Engelman
Journal:  Cancer Discov       Date:  2012-01-16       Impact factor: 39.397

3.  Resistance to selective BRAF inhibition can be mediated by modest upstream pathway activation.

Authors:  Fei Su; William D Bradley; Qiongqing Wang; Hong Yang; Lizhong Xu; Brian Higgins; Kenneth Kolinsky; Kathryn Packman; Min Jung Kim; Kerstin Trunzer; Richard J Lee; Kathleen Schostack; Jade Carter; Thomas Albert; Soren Germer; Jim Rosinski; Mitchell Martin; Mary Ellen Simcox; Brian Lestini; David Heimbrook; Gideon Bollag
Journal:  Cancer Res       Date:  2011-12-28       Impact factor: 12.701

4.  Antitumor activity of BRAF inhibitor vemurafenib in preclinical models of BRAF-mutant colorectal cancer.

Authors:  Hong Yang; Brian Higgins; Kenneth Kolinsky; Kathryn Packman; William D Bradley; Richard J Lee; Kathleen Schostack; Mary Ellen Simcox; Scott Kopetz; David Heimbrook; Brian Lestini; Gideon Bollag; Fei Su
Journal:  Cancer Res       Date:  2011-12-16       Impact factor: 12.701

5.  Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells.

Authors:  Jihye Yun; Carlo Rago; Ian Cheong; Ray Pagliarini; Philipp Angenendt; Harith Rajagopalan; Kerstin Schmidt; James K V Willson; Sandy Markowitz; Shibin Zhou; Luis A Diaz; Victor E Velculescu; Christoph Lengauer; Kenneth W Kinzler; Bert Vogelstein; Nickolas Papadopoulos
Journal:  Science       Date:  2009-08-06       Impact factor: 47.728

6.  Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial.

Authors:  Arnaud D Roth; Sabine Tejpar; Mauro Delorenzi; Pu Yan; Roberto Fiocca; Dirk Klingbiel; Daniel Dietrich; Bart Biesmans; György Bodoky; Carlo Barone; Enrique Aranda; Bernard Nordlinger; Laura Cisar; Roberto Labianca; David Cunningham; Eric Van Cutsem; Fred Bosman
Journal:  J Clin Oncol       Date:  2009-12-14       Impact factor: 44.544

7.  Resistance to BRAF inhibition in BRAF-mutant colon cancer can be overcome with PI3K inhibition or demethylating agents.

Authors:  Muling Mao; Feng Tian; John M Mariadason; Chun C Tsao; Robert Lemos; Farshid Dayyani; Y N Vashisht Gopal; Zhi-Qin Jiang; Ignacio I Wistuba; Xi M Tang; William G Bornman; Gideon Bollag; Gordon B Mills; Garth Powis; Jayesh Desai; Gary E Gallick; Michael A Davies; Scott Kopetz
Journal:  Clin Cancer Res       Date:  2012-12-18       Impact factor: 12.531

Review 8.  Molecular origins of cancer: Molecular basis of colorectal cancer.

Authors:  Sanford D Markowitz; Monica M Bertagnolli
Journal:  N Engl J Med       Date:  2009-12-17       Impact factor: 91.245

9.  Development of a mouse model for sporadic and metastatic colon tumors and its use in assessing drug treatment.

Authors:  Kenneth E Hung; Marco A Maricevich; Larissa Georgeon Richard; Wei Y Chen; Michael P Richardson; Alexandra Kunin; Roderick T Bronson; Umar Mahmood; Raju Kucherlapati
Journal:  Proc Natl Acad Sci U S A       Date:  2010-01-04       Impact factor: 11.205

10.  A robust genomic signature for the detection of colorectal cancer patients with microsatellite instability phenotype and high mutation frequency.

Authors:  Sun Tian; Paul Roepman; Vlad Popovici; Magali Michaut; Ian Majewski; Ramon Salazar; Cristina Santos; Robert Rosenberg; Ulrich Nitsche; Wilma E Mesker; Sjoerd Bruin; Sabine Tejpar; Mauro Delorenzi; Rene Bernards; Iris Simon
Journal:  J Pathol       Date:  2012-10-12       Impact factor: 7.996
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  44 in total

Review 1.  Colorectal cancer models for novel drug discovery.

Authors:  Daniel Golovko; Dmitriy Kedrin; Ömer H Yilmaz; Jatin Roper
Journal:  Expert Opin Drug Discov       Date:  2015-08-21       Impact factor: 6.098

Review 2.  Serrated colorectal cancer: Molecular classification, prognosis, and response to chemotherapy.

Authors:  Oscar Murcia; Miriam Juárez; Eva Hernández-Illán; Cecilia Egoavil; Mar Giner-Calabuig; María Rodríguez-Soler; Rodrigo Jover
Journal:  World J Gastroenterol       Date:  2016-04-07       Impact factor: 5.742

Review 3.  Targeting mTOR network in colorectal cancer therapy.

Authors:  Xiao-Wen Wang; Yan-Jie Zhang
Journal:  World J Gastroenterol       Date:  2014-04-21       Impact factor: 5.742

4.  HDAC Inhibition Overcomes Acute Resistance to MEK Inhibition in BRAF-Mutant Colorectal Cancer by Downregulation of c-FLIPL.

Authors:  Robbie Carson; Basak Celtikci; Patrick G Johnston; Sandra Van Schaeybroeck; Cathy Fenning; Arman Javadi; Nyree Crawford; Lucia Perez Carbonell; Mark Lawler; Daniel B Longley
Journal:  Clin Cancer Res       Date:  2015-03-26       Impact factor: 12.531

Review 5.  Targeting BRAF mutant metastatic colorectal cancer: clinical implications and emerging therapeutic strategies.

Authors:  Jeanne Tie; Jayesh Desai
Journal:  Target Oncol       Date:  2014-08-15       Impact factor: 4.493

Review 6.  RAS and BRAF in metastatic colorectal cancer management.

Authors:  Jun Gong; May Cho; Marwan Fakih
Journal:  J Gastrointest Oncol       Date:  2016-10

7.  Inhibition of HSP90 by AT13387 delays the emergence of resistance to BRAF inhibitors and overcomes resistance to dual BRAF and MEK inhibition in melanoma models.

Authors:  Tomoko Smyth; Kim H T Paraiso; Keisha Hearn; Ana M Rodriguez-Lopez; Joanne M Munck; H Eirik Haarberg; Vernon K Sondak; Neil T Thompson; Mohammad Azab; John F Lyons; Keiran S M Smalley; Nicola G Wallis
Journal:  Mol Cancer Ther       Date:  2014-10-27       Impact factor: 6.261

8.  Dovitinib (TKI258), a multi-target angiokinase inhibitor, is effective regardless of KRAS or BRAF mutation status in colorectal cancer.

Authors:  Choong-Kun Lee; Myung Eun Lee; Won Suk Lee; Jeong Min Kim; Kyu Hyun Park; Tae Soo Kim; Kang Young Lee; Joong Bae Ahn; Hyun Cheol Chung; Sun Young Rha
Journal:  Am J Cancer Res       Date:  2014-12-15       Impact factor: 6.166

9.  Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer.

Authors:  Jatin Roper; Mark J Sinnamon; Erin M Coffee; Peter Belmont; Lily Keung; Larissa Georgeon-Richard; Wei Vivian Wang; Anthony C Faber; Jihye Yun; Ömer H Yilmaz; Roderick T Bronson; Eric S Martin; Philip N Tsichlis; Kenneth E Hung
Journal:  Cancer Lett       Date:  2014-02-24       Impact factor: 8.679

10.  Challenges in secondary analysis of high throughput screening data.

Authors:  Aurora S Blucher; Shannon K McWeeney
Journal:  Pac Symp Biocomput       Date:  2014
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