Title:Ipilimumab and Vemurafenib: Two Different Routes for Targeting Melanoma
VOLUME: 13 ISSUE: 8
Author(s):Ana Burgeiro, Faustino Mollinedo and Paulo J. Oliveira
Affiliation:Center for Neuroscience and Cell Biology, Largo Marquês de Pombal, University of Coimbra, 3004-517 Coimbra, Portugal.
Keywords:BRAFV600E mutation, Clinical investigation, Immunotherapy, Ipilimumab, Melanoma, Vemurafenib.
Abstract:Melanoma, a malignant tumor of melanocytes, causes the majority (75%) of all skin cancer-related deaths. The
overall efficacy of different anti-cancer therapies on metastatic melanoma is quite limited, due to its high resistance to all
forms of conventional treatments, including chemotherapy, radiotherapy and immunotherapy, leading to low patient
survival rates.
The present review identifies possible strategies for the treatment of advanced melanoma and describes two novel agents,
Ipilimumab and Vemurafenib, which may now be useful for clinical practice.
Ipilimumab, a humanized, IgG1 monoclonal antibody, acts through immune-modulation since it blocks cytotoxic Tlymphocyte-
associated antigen-4 (CTLA-4), producing favourable antitumor immune system responses and reducing
tolerance to tumor-associated antigens. Vemurafenib is a novel oral small-molecule kinase inhibitor with high selectivity
and efficacy toward a specific mutated oncogenic BRAF-signalling mediator. The mechanism of action of Vemurafenib
involves selective inhibition of the mutated BRAFV600E kinase that leads to reduced signalling through the aberrant MAPK
pathway. However, as patients commonly develop Vemurafenib resistance, clinical trials of Vemurafenib in combination
with Ipilimumab or other targeted or cytotoxic chemotherapeutic agents may provide more effective regimens with longterm
clinical benefits, emphasizing the importance of simultaneously targeting several pathways.
As both drugs had only modest effects on median survival, new therapeutic combinations are needed, such as BRAF
inhibitors with MEK inhibitors or combinations of immunomodulators and pathway inhibitors. Such strategies should
have the potential of maximizing antitumor effect while minimizing and improving clinical benefit. Nevertheless, these
two new agents open a promising view into an effective management of melanoma.
