HIV Drug Could Re-sensitize Therapy-resistant Melanoma
Source: Oncology Nurse Advisor, March 2016
The expression of the PAX3 and MITF genes in melanoma can cause early, nonmutational, reversible drug resistance. Melanoma tissues that express these genes can then later develop mutational, irreversible drug resistance. The HIV drug nelfinavir can prevent this targeted therapy resistance in melanoma, according to a study published in Cancer Cell.1
Nelfinivar was predicted to inhibit both PAX3 and MITF. The drug is a protease inhibitor with known antiretroviral activity.
This study examined melanoma tissue samples from 11 patients undergoing vemurafenib or dabrafenib and trametinib therapy. Samples were taken at day 0 and at days 10 to 14 of treatment. Samples were also taken at time of progression if applicable.
In patient tissue samples, cell cultures, and samples from a mouse model of melanoma, researchers revealed increased expression in PAX3 and MITF in the development of targeted therapy resistance. An immunofluorescence-based drug screen on 640 FDA-approved drugs that could inhibit PAX3 and MITF expression revealed 7 drugs that inhibit both genes. Nelfinivar had the strongest predicted effect of all 7 drugs.