BRAF targeted therapy changes the treatment paradigm in melanoma
Therapeutic advances in melanoma seem on the horizon, with the identification of BRAF as a principal therapeutic target. The authors describe the scientific basis for the targeting of BRAF mutations in cancer, the early clinical data with BRAF inhibitors, and how combinatorial therapies may address...
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| Vydáno v: | Nature reviews. Clinical oncology Ročník 8; číslo 7; s. 426 - 433 |
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| Hlavní autoři: | , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
London
Nature Publishing Group UK
01.07.2011
Nature Publishing Group |
| Témata: | |
| ISSN: | 1759-4774, 1759-4782, 1759-4782 |
| On-line přístup: | Získat plný text |
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| Shrnutí: | Therapeutic advances in melanoma seem on the horizon, with the identification of BRAF as a principal therapeutic target. The authors describe the scientific basis for the targeting of
BRAF
mutations in cancer, the early clinical data with BRAF inhibitors, and how combinatorial therapies may address the current limitations of their use in the clinic.
After decades of stagnation, recent therapeutic advances in melanoma seem on the horizon. The discovery of the genetic underpinnings of this historically refractory disease has exposed potential targets for therapy,
BRAF
mutations being principal among them. In the 8 years following the discovery of
BRAF
mutations in 50–60% of advanced melanomas, only recently have potent and selective inhibitors of this intracellular signaling molecule shown efficacy from early clinical testing. Vemurafenib (PLX4032) and GSK2118436, two orally available and well tolerated agents are on the verge of transforming the landscape of melanoma therapy based on the promising results of their respective phase I, II, and III trials.
Key Points
BRAF
is the most frequently mutated oncogene in melanoma
Selective BRAF inhibitors have produced tumor regression in the vast majority of patients with metastatic melanoma whose tumors harbor activating
BRAF
mutations
Selective BRAF inhibitors are associated with the appearance of keratinocyte proliferations in patients; upregulation of the MAPK pathway in normal cells observed
in vitro
may explain this observation
Additional oncogenic events are associated with
BRAF
mutations and may provide rational additional targets for combination therapy
Preliminary evidence suggests that selective BRAF inhibitors may complement immunotherapy by upregulating antigen expression but without inhibiting T-cell function |
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| Bibliografie: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| ISSN: | 1759-4774 1759-4782 1759-4782 |
| DOI: | 10.1038/nrclinonc.2011.69 |