Successful rechallenge in two patients with BRAF-V600-mutant melanoma who experienced previous progression during treatment with a selective BRAF inhibitor

Melanoma Research
Amélie Clémentine SeghersBart Neyns

Abstract

The v-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene is mutated at position 600 in about 50% of melanoma. Mutant BRAF activates the downstream effectors of the RAS-RAF-MEK-MAPK pathways and is a driver oncogene in these melanoma cells. Selective BRAF-V600 inhibitors (vemurafenib, dabrafenib) have high antitumor activity against BRAF-V600-mutant melanoma with objective tumor response rates. Resistance, however, develops within less than a year in the majority of patients. Several different mechanisms have been found to mediate acquired resistance, but these do not involve the occurrence of secondary mutations in the BRAF gene. Two patients with BRAF-V600E mutant melanoma who had documented progression during treatment with dabrafenib/GSK1120212 and dabrafenib, respectively, were rechallenged with dabrafenib and vemurafenib after a treatment-free interval of 8 and 4 months during which further progression was documented. Both patients showed a marked clinical response and, in both, objective tumor regression (qualifying as a mixed and a partial response according to RECIST) was documented. These two case observations indicate that resistance to BRAF-selective inhibitors can be reversible following treatment interruption.

References

Sep 3, 2004·The New England Journal of Medicine·Hensin TsaoArthur J Sober
Nov 18, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Charles M BalchVernon K Sondak
Apr 22, 2010·Journal of Translational Medicine·Jonas N SøndergaardAntoni Ribas
Jun 8, 2010·The New England Journal of Medicine·F Stephen HodiWalter J Urba
Sep 8, 2010·The New England Journal of Medicine·Keith T FlahertyPaul B Chapman
Nov 26, 2010·Nature·Cory M JohannessenLevi A Garraway
Dec 1, 2010·Cancer Chemotherapy and Pharmacology·Mrinal M Gounder, Robert G Maki
Dec 21, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Begoña Comin-AnduixAntoni Ribas
Mar 9, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nikhil WagleLevi A Garraway
Jun 7, 2011·The New England Journal of Medicine·Paul B ChapmanUNKNOWN BRIM-3 Study Group
Dec 2, 2011·Cancer Research·Jessie VillanuevaMeenhard Herlyn
Dec 14, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·James S WilmottRichard A Scolyer
Jan 5, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alexander Marzuka Alcalá, Keith T Flaherty

❮ Previous
Next ❯

Citations

Jun 5, 2013·Journal of Translational Medicine·Paolo A AsciertoMagdalena Thurin
Sep 23, 2014·Trends in Biochemical Sciences·Chong Sun, René Bernards
Jun 18, 2014·FEBS Letters·Botond CsehManuela Baccarini
Oct 29, 2014·Journal of Translational Medicine·Paolo A AsciertoMagdalena Thurin
Nov 29, 2015·Seminars in Oncology·Keara L RedmondSandra Van Schaeybroeck
Jun 2, 2015·Nature Medicine·Giulia SiravegnaAlberto Bardelli
May 2, 2015·The Journal of Clinical Investigation·Stefan GrossKlaus P Hoeflich
Dec 4, 2014·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·S SchmidM Früh
Dec 5, 2012·Cancer Treatment Reviews·C M NijenhuisJ H Beijnen
Jul 25, 2014·The Annals of Pharmacotherapy·Anthony JarkowskiVan Anh Trinh
Nov 22, 2013·The Annals of Pharmacotherapy·Van Anh TrinhKevin B Kim
Mar 3, 2017·Nature Reviews. Clinical Oncology·Giulia SiravegnaAlberto Bardelli
Jun 25, 2017·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Tony IbrahimCaroline Robert
Dec 2, 2017·Journal of Cell Communication and Signaling·Heinz Hammerlindl, Helmut Schaider
Dec 16, 2017·International Journal of Cancer. Journal International Du Cancer·Claire A MartinKaren E Sheppard
Mar 11, 2015·Therapeutic Advances in Medical Oncology·Sarah J Welsh, Pippa G Corrie
Nov 5, 2014·Therapeutic Advances in Medical Oncology·Andrew J DooleyMark R Middleton
Dec 22, 2015·Biomarkers in Cancer·Amit Dipak AminJonathan H Schatz
Jul 20, 2018·Frontiers of Medicine·Liqin Wang, Rene Bernards
Apr 13, 2017·Journal of the European Academy of Dermatology and Venereology : JEADV·V C AmannS M Goldinger
Oct 5, 2017·Nature·Xiangjun KongDaniel S Peeper
Jan 17, 2020·Cells·Ufuk DegirmenciJiancheng Hu
Nov 29, 2017·Oncotarget·Grace J YoungIan F Dunn
Jun 25, 2020·Cancers·Paolo BeccoMassimo Aglietta
Jul 16, 2013·Melanoma Research·Pierre GuerreschiLaurent Mortier
Jan 5, 2019·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·D ViñalE Espinosa
Sep 24, 2015·Melanoma Research·Jennifer RouxCéleste Lebbe
Aug 1, 2015·Melanoma Management·Samantha BowyerPaul Lorigan
Mar 30, 2020·Melanoma Research·Bożena Cybulska-StopaPiotr Rutkowski
Jul 3, 2020·Pathology Oncology Research : POR·Viktoria KoroknaiMargit Balazs

❮ 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.