Identification of potential new therapeutic targets and treatment strategies in melanoma cells with different phenotypes

• Grant number: 20/15868-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2021
• End date: June 30, 2022
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Miriam Galvonas Jasiulionis
• Grantee: Sabrina Meira de Neiva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Melanoma is a neoplastic disease that affects melanocytes, the second most abundant cell population in the epidermis, responsible for the production of melanin and protection from UV radiation. It is the subtype of skin cancer that most leads patients to death due to its great metastatic potential and its ability to develop resistance to treatments that are currently available. Most of the treated melanomas do not show an effective response to drugs or have a recurrence due to the proliferation of a resistant cell population. This resistance has already been related to several genetic and epigenetic factors, such as the variation between different cellular phenotypes, growth factors such as TGF-Beta, reactivation of metabolic pathways, and mutations in genes such as BRAF and MEK. Despite this, an effective way to overcome this great difficulty that is found in most patients has not yet been discovered. Relatively new drugs have a good perspective when compared to drugs such as dacarbazine, as is the case with BRAF inhibitors or immunotherapies such as anti-PD-1 and anti-CTLA-4. Despite this, there are still a large number of patients, which do not respond or have a recurrence after a certain period. The knowledge about the molecular characteristics of melanoma and its tumor microenvironment facilitates an approach aimed at characterizing new therapeutic targets. A study that assesses the effects of combined therapy may show new characteristics of the behavior of melanoma when subjected to a stressful environment, which also highlights new factors related to the development of resistance. (AU)