Is combination therapy the next step to overcome resistance and reduce toxicities in melanoma?

Abstract:

:In the last few years, several drugs targeting signalling proteins critical for melanoma entered clinical evaluation. In 2011 vemurafenib (Zelboraf®, F. Hoffman-La Roche Ltd.) was approved for BRAF V600-positive melanoma and showed high overall response rates (48-53%). However recent results from a phase II clinical trial also showed that the median duration of response was 6.7months and median progression free survival was 6.8months with tumour relapse. Resistance to targeted agents is quite common and understanding of the underlying molecular mechanisms might predict response or failure. The knowledge of the mechanisms involved in intrinsic and acquired resistance to mutated BRAF is increasing swiftly. Subsequently the elucidation of these mechanisms resulted in the development of rational combination therapies to overcome toxicity and resistance. These combination therapies will be discussed.

journal_name

Cancer Treat Rev

journal_title

Cancer treatment reviews

authors

Nijenhuis CM,Haanen JB,Schellens JH,Beijnen JH

doi

10.1016/j.ctrv.2012.10.006

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

305-12

issue

4

eissn

0305-7372

issn

1532-1967

pii

S0305-7372(12)00213-7

journal_volume

39

pub_type

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