RESUMO
BACKGROUND: Anti-cancer cytotoxic treatments like platinum-derived compounds often show low therapeutic efficacy, high-risk side effects and resistance. Hence, targeted treatments designed to attack only tumour cells avoiding these harmful side effects are highly needed in clinical practice. Due to this, precision oncology has arisen as an approach to specifically target alterations present only in cancer cells, minimising side effects for patients. It involves the use of molecular biomarkers present in each kind of tumour for diagnosis, prognosis and treatment. Since these biomarkers are specific for each cancer type, physicians use them to stratify, diagnose or take the best therapeutic options for each patient depending on the features of the specific tumour. AIM: This review aims to describe the current situation, limitations, advantages and perspectives about precision oncology in Latin America. MAIN BODY: For many years, many biomarkers have been used in a clinical setting in developed countries. However, in Latin American countries, their broad application has not been affordable partially due to financial and technical limitations associated with precarious health systems and poor access of low-income populations to quality health care. Furthermore, the genetic mixture in Latin American populations could generate differences in treatment responses from one population to another (pharmacoethnicity) and this should be evaluated before establishing precision therapy in particular populations. Some research groups in the region have done a lot of work in this field and these data should be taken as a starting point to establish networks oriented to finding clinically useful cancer biomarkers in Latin American populations. CONCLUSION: Latin America must create policies allowing excluded populations to gain access to health systems and next generation anti-cancer drugs, i.e. high-cost targeted therapies to improve survival. Also, cancer clinical research must be oriented to establish cancer biomarkers adapted to specific populations with different ethnicity, allowing the improvement of patient outcomes.
RESUMO
BACKGROUND: Cu/Zn superoxide dismutases (SODs) like the extracellular SOD3 and cytoplasmic SOD1 regulate cell proliferation by generating hydrogen peroxide (H2O2). This pro-oxidant inactivates essential cysteine residues in protein tyrosine phosphatases (PTP) helping receptor tyrosine kinase activation by growth factor signaling, and further promoting downstream MEK/ERK linked cell proliferation. Disulfiram (DSF), currently in clinical cancer trials is activated by copper chelation, being potentially capable of diminishing the copper dependent activation of MEK1/2 and SOD1/SOD3 and promoting reactive oxygen species (ROS) toxicity. However, copper (Cu) overload may occur when co-administered with DSF, resulting in toxicity and mutagenicity against normal tissue, through generation of the hydroxyl radical (â¢OH) by the Fenton reaction. PURPOSE: To investigate: a) whether sub-toxic DSF efficacy can be increased without Cu overload against human melanoma cells with unequal BRAF(V600E) mutant status and Her2-overexpressing SKBR3 breast cancer cells, by increasing H2O2 from exogenous SOD; b) to compare the anti-tumor efficacy of DSF with that of another clinically used copper chelator, tetrathiomolybdate (TTM). RESULTS: a) without copper supplementation, exogenous SOD potentiated sub-toxic DSF toxicity antagonized by sub-toxic TTM or by the anti-oxidant N-acetylcysteine; b) exogenous glucose oxidase, another H2O2 generator resembled exogenous SOD in potentiating sub-toxic DSF. CONCLUSIONS: potentiation of sub-lethal DSF toxicity by extracellular H2O2 against the human tumor cell lines investigated, only requires basal Cu and increased ROS production, being unrelated to non-specific or TTM copper chelator sequestration. SIGNIFICANCE: These findings emphasize the relevance of extracellular H2O2 as a novel mechanism to improve disulfiram anticancer effects minimizing copper toxicity.