In a recent study titled “Proteomic Profile and In Silico Analysis in Metastatic Melanoma with and without BRAF Mutation”, published in the PlosOne journal, a team of researchers led by Dr. Vito Michele Garrisi from the Istituto Tumori “Giovanni Paolo II”, Bari, Italy, sought to discover novel candidate biomarkers predictive of melanoma treatment.
Currently, BRAF inhibitors, such as vemurafenib and dabrafenib, are the standard of care for metastatic melanoma patients that carry BRAF V600, as opposed to BRAF wild type patients, who mainly undergo chemotherapy.
The researchers wanted to test surface enhanced laser desorption ionization time of flight mass spectrometry (SELDI ToF MS), a method enabling biomarker discovery, in the identification of new candidate peptides that could be used as predicative biomarkers of response or resistance to treatment.
A total of 39 patients diagnosed with stage IV metastatic melanoma, and who were treatment naïve, were enrolled in the trial for a period of 3 years.
Among them, 19 BRAF V600 patients received vemurafenib at 960 mg twice daily until progression or unacceptable toxicity. The other 20 patients (17 BRAF wild type patients and 3 BRAF V600E) received chemotherapy every 3 weeks up to a maximum of 9 cycles.
The results showed that in patients presenting different BRAF status, there were 5 peptides significantly deregulated, with a particular peptide peak, m/z 9176, associated with the BRAF mutation.
At baseline, 2 peptides, m/z 6411, 4075, were significantly up-regulated after chemotherapy and 4 peptides, m/z 5900, 12544, 49124 and 11724, were consistently up-regulated in longer versus shorter responders to vemurafenib.
After patients responded to treatment, the team verified that 3 peptides, m/z 4658, 18639, and 9307, were down-regulated, while another 3, m/z 9292, 7765 and 9176, were up-regulated in chemotherapy and vemurafenib responder patients.
Furthermore, when patients were treated with vemurafenib, there were 16 peaks differentially regulated during response compared to baseline.
Additionally analysis identified proteins involved in different malignant processes such as invasiveness (SLAIN1), resistance (ABCC12) and apoptosis (RBM10, TOX3, MTEFD1, TSPO2).
These results stress the fact that more biomarkers are necessary to improve melanoma treatment strategies.
As the authors write in their study, “Therapeutic decisions are made selectively, tailoring therapy according to specific patient and tumor characteristics. Currently in metastatic melanoma, beyond “baseline” evaluation of BRAF mutations in the tumor sample to identify patients who are candidates to receive Vemurafenib, clinicians have no minimally invasive pharmacodynamic biomarkers in routine use to identify those patients most likely to benefit and to early monitor treatment efficacy. Serum biomarkers of melanoma are still awaited and the clinical significance of many evaluated peptides remains a matter of debate.”
