A less common but more serious cutaneous manifestation
following BRAF inhibitor therapy is the induction or differentiation
of melanocytic lesions considered to arise via wild
type paradoxical MAPK pathway stimulation by increased
activity upstream. Dalle et al reported on 5 BRAF wild
type melanomas and one dysplastic nevus in four patients
undergoing BRAF inhibitor treatment.6 Chapman et al documented
5 cases in 464 patients undergoing treatment with
a RAF inhibitor.7 Zimmer et al investigated 19 patients with
22 changing melanocytic lesions or secondary melanomas
treating with a RAF inhibitor, and their genetic investigation
of the new primary melanomas were found to be BRAF negative
with increased levels of cyclin D1 and pAKT, which may
suggest other proliferative pathways aside from MAPK may
be involved.5 Early detection and treatment of melanoma is
vital as it imparts a greatly improved prognosis.
The patient’s 3-year progression free survival is evidence of
exceptional therapeutic benefit. Prior treatment with dacarbazine
gave a median overall survival prognosis of slightly more
than 6 months.3 Unfortunately, monotherapy for these cancers
limits the therapeutic window of susceptibility and leads to resistance
with multiple mechanisms upstream and downstream
