Combination of chemotherapy with BRAF inhibitors effective in treating metastatic melanoma : Study

Combination of chemotherapy with BRAF inhibitors effective in treating metastatic melanoma : Study
Combining BRAF oncogene inhibitors and chemotherapy may be a very effective strategy for fighting metastatic melanoma, finds a new study published in the journal Oncogene.

The study was conducted by researchers from the Hospital del Mar Medical Research Institute (IMIM), Hospital del Mar, and the CIBER Cancer (CIBERONC), in collaboration with the Bellvitge Medical Research Institute (ICO-IDIBELL).

The study analysed the effect of combining the two types of treatment in cases of malignant melanoma. In the previous studies, these researchers had demonstrated the efficacy of blocking BRAF oncogene expression to reduce the ability of colon and rectal cancer cells to repair after chemotherapy treatment. The researchers tested the two treatments both separately and together in mice and in tumour cells in vitro. The combination of the two approaches proved to be superior in all trials after one week of treatment.

“We have demonstrated the therapeutic potential of combining the two treatments to eradicate cancer cells. This strategy not only prevents the appearance of resistance to one of the approaches, but also offers a new therapeutic perspective for patients with mutations affecting the BRAF oncogene,” explained Dr Lluis Espinosa, a researcher at the IMIM-Hospital del Mar and CIBERONC, and author of the study.

The study also indicates that chemotherapy administered at low doses helps reduce its toxicity.  When combined with the standard treatment with BRAF inhibitor the combination therapy can have an enormous effect on the progression of metastatic melanoma. Furthermore, the benefits were maintained after the end of treatment. Because the combined treatment eliminates tumour cells rather than stopping their growth, it would also avoid lengthy treatments and the possible development of resistance.

By combining low-dose chemotherapy, which has very low toxicity, with BRAF inhibitors, we damage the cell’s DNA with the chemotherapy while at the same time we prevent the cell from repairing itself thanks to the BRAF inhibitors. This not only enhances the effect of each of the treatments, but it might make the effect irreversible,” commented Dr Fernando Gallardo, head of the dermatology department and author of the study.

One of the main problems encountered with BRAF inhibitor treatment, the gold standard approach to this disease, is that the cancer cells re-grow and become resistant to this therapy, as the inhibitor only stops them, and does not eliminate them. The possibility of using this in combination with chemotherapy could eliminate the problem of certain resistance and relapse.