Optimizing targeted therapeutic development: analysis of a colorectal cancer patient population with the BRAF(V600E) mutation

International Journal of Cancer. Journal International Du Cancer
Jeanne TieJayesh Desai

Abstract

BRAF(V600E) mutations are found in 10% of colorectal cancers (CRCs). The low frequency of this mutation therefore makes it a challenging target for drug development, unless subsets of patients with higher rates of BRAF(V600E) can be defined. Knowledge of the concordance between primary-metastasis pairs and the impact of BRAF(V600E) on outcome would also assist in optimal drug development. We selected primary CRCs from 525 patients (stages I-IV) evenly matched for age (<70 and ≥70), gender and tumor location (right, left and rectum), and 81 primary-metastasis pairs. BRAF(V600E), KRAS mutation and microsatellite instability (MSI) were determined and correlated with clinical features and patient outcomes. In multivariate analyses, increasing patient age (p = 0.04), female gender (p = 0.0005) and right-sided tumor location (p < 0.0001) were independently associated with BRAF(V600E). The prevalence of BRAF(V600E) was considerably higher in older (age > 70) females with KRAS wild-type right-sided colon cancers (50%) compared to the unselected cohort (10%). BRAF(V600E) was associated with inferior overall survival in metastatic CRC (HR = 2.02; 95% CI 1.26-3.26), particularly evident in patients treated with chemotherapy, and is indepe...Continue Reading

References

Sep 1, 1988·The New England Journal of Medicine·B VogelsteinJ L Bos
May 3, 1987·Nature·J L BosB Vogelstein
Apr 1, 1996·Current Opinion in Cell Biology·C J Marshall
Aug 1, 1997·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·T Joneson, D Bar-Sagi
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·M L VeiglS D Markowitz
Oct 21, 1998·Oncogene·S L CampbellC J Der
Feb 13, 2001·The American Journal of Pathology·J AlexanderS R Hamilton
Jul 4, 2001·International Journal of Cancer. Journal International Du Cancer·B BaisseJ Benhattar
Jun 18, 2002·Nature·Helen DaviesP Andrew Futreal
Aug 29, 2002·Nature·Harith RajagopalanVictor E Velculescu
Dec 23, 2003·Carcinogenesis·Karin FransénPeter Söderkvist
Jan 22, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Guoren DengYoung S Kim
May 3, 2005·The Lancet Oncology·Jing Yuan Fang, Bruce C Richardson
Jun 1, 2005·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A RussoN Gebbia
Jul 7, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Steven J CohenNeal J Meropol
Jul 19, 2005·Cancer Research·Wade S SamowitzMartha L Slattery
Aug 29, 2007·Oncogene·C MichaloglouD S Peeper
Jan 19, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Astrid LièvrePierre Laurent-Puig
Jan 29, 2008·International Journal of Cancer. Journal International Du Cancer·Ludovic BaraultFrancoise Piard
Sep 2, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Salvatore ArtaleSalvatore Siena
Oct 24, 2008·The New England Journal of Medicine·Christos S KarapetisJohn R Zalcberg
Nov 13, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Federica Di NicolantonioAlberto Bardelli
Jan 7, 2009·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Glenn E PalomakiStephen N Thibodeau
Apr 3, 2009·The New England Journal of Medicine·Eric Van CutsemPhilippe Rougier
Jul 3, 2009·The New England Journal of Medicine·Jolien TolCornelis J A Punt
Oct 28, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lars Henrik JensenDorthe G Crüger
Dec 17, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Arnaud D RothFred Bosman

❮ Previous
Next ❯

Citations

Jun 15, 2011·The New England Journal of Medicine·Enrico TiacciBrunangelo Falini
Jun 27, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M VoskoboynikP Gibbs
Nov 1, 2011·PloS One·Hazem El-OstaRazelle Kurzrock
Apr 26, 2014·World Journal of Gastroenterology : WJG·Jung Ho Kim, Gyeong Hoon Kang
Oct 3, 2013·Clinical & Experimental Metastasis·Matthew K H HongChristopher M Hovens
Jul 19, 2013·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M K BoisenB V Jensen
Jan 19, 2016·Future Oncology·Daniel H Ahn, Richard M Goldberg
Jul 15, 2015·Expert Review of Molecular Diagnostics·Christos S KarapetisMichael Z Michael
May 16, 2015·Expert Review of Molecular Diagnostics·Mario ScartozziStefano Cascinu
Nov 18, 2015·British Journal of Cancer·Fotios LoupakisEmilio Bria
Jul 15, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C CremoliniF Pietrantonio
Aug 26, 2015·British Journal of Cancer·Robert N JorissenOliver M Sieber
Jul 6, 2012·Critical Reviews in Oncology/hematology·Stephen J ClarkeJosep Tabernero
Jun 28, 2016·Biochimica Et Biophysica Acta·Paulo MatosPeter Jordan
Oct 19, 2016·Expert Review of Pharmacoeconomics & Outcomes Research·Taehwan ParkDong-Churl Suh
Dec 28, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Hui-li Wong, Peter Gibbs
Jan 25, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ben TranLillian L Siu
Sep 24, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ryan B CorcoranScott Kopetz
Oct 16, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Scott KopetzLeonard Saltz
Jan 2, 2014·Therapeutic Advances in Gastroenterology·Christopher M Hocking, Timothy J Price
May 1, 2018·Expert Review of Molecular Diagnostics·Eleonora LaiMario Scartozzi
Oct 15, 2013·The Journal of Pathology·Jérôme GalonFranck Pagès
Nov 2, 2018·Expert Review of Anticancer Therapy·Per PfeifferCamilla Qvortrup
Aug 26, 2018·International Journal of Cancer. Journal International Du Cancer·Levent DizdarAndreas Krieg
Aug 11, 2012·British Journal of Cancer·B KinnersleyUNKNOWN Colon Cancer Family Registry
Aug 22, 2013·Virchows Archiv : an International Journal of Pathology·Alexandra ThielAri Ristimäki
May 15, 2013·Oncology Reports·Thais Gulim De CarvalhoAndre Luiz Vettore
Jul 11, 2019·Nature Reviews. Clinical Oncology·Anita SveenRagnhild A Lothe
Aug 9, 2018·Scientific Reports·Abril Sánchez-BotetJosep Clotet
May 9, 2014·International Journal of Cancer. Journal International Du Cancer·Marta SchirripaAlfredo Falcone
Feb 11, 2015·World Journal of Gastroenterology : WJG·Ju-Xiang YeXue-Ying Shi
Oct 19, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·E Sanz-GarciaJ Tabernero

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.