357certain BRAF mutations. Simultaneously, the agency approved BioMérieux’s
THxID-BRAF companion diagnostic, a real-time PCR assay designed to identify
patients whose tumors harbor BRAF V600E and BRAF V600K mutations, and thus
are best responders to these agents. Approximately half of melanoma patients have
tumors driven by BRAF mutations.
BRAF inhibitor Sorafenib has not shown selective affi nity against tumors carry-
ing BRAF mutations in clinical trials, whether used alone or in combination with
other chemotherapies. It is possible that non-BRAF side effects of sorafenib limit
the likelihood of achieving drug concentrations that are high enough to inhibit V600
mutation.
Management of Drug-Resistant Metastatic Melanoma
BRAF inhibitors Vemurafenib and Dabrafenib markedly inhibit tumor growth and
advance patients’ overall survival but this response is almost inevitably followed by
complete tumor relapse due to drug resistance hampering the encouraging initial
responses. Several mechanisms of resistance within and outside the MAPK path-
way have now been uncovered and have paved the way for clinical trials of combi-
nation therapies to try and overcome tumor relapse. It is apparent that personalized
treatment management will be required in this new era of targeted treatment.
Circulating tumor cells (CTCs) provide an easily accessible means of monitoring
patient relapse and several new approaches are available for the molecular charac-
terization of CTCs. Thus CTCs provide a monitoring tool to evaluate treatment
effi cacy and early detection of drug resistance in real time. Advances in the molecu-
lar analysis of CTCs may provide insight into new avenues of approaching thera-
peutic options that would benefi t personalized melanoma management (Klinac
et al. 2013 ).
Vaccine for Malignant Melanoma Based on Heat Shock Protein
Autologous tumor-derived HSP gp96 peptide complex (HSPPC-96, Prophage ® ,
vitespen) vaccine (Agenus Inc) is emerging as a tumor- and patient-specifi c cancer
vaccine, with confi rmed activity in several malignancies. It has been tested in phase
III clinical trials in advanced melanoma with evidence for effi cacy in patients with
earlier stage disease. HSPPC-96-based vaccine demonstrated an excellent safety
profi le, thus emerging as a novel therapeutic approach with a suggestive role in
cancer therapy. Further investigations are needed to understand the biological basis
of immune functions in order to improve the clinical outcome of HSP-based cancer
therapy. In the near future, the combination of HSP-based vaccines with other bio-
logical compounds might represent a successful strategy in the therapy of advanced
melanoma.
Personalized Management of Cancers of Various Organs