The Roles of ROS in Cancer Heterogeneity and Therapy

Autor(es)

de Sa Junior, Paulo Luiz ^[1] ; Dias Camara, Diana Aparecida ^{[2, 3]} ; Porcacchia, Allan Saj ^[4] ; Moreira Fonseca, Pamela Maria ^[1] ; Jorge, Salomao Doria ^[5] ; Araldi, Rodrigo Pinheiro ^[2] ; Ferreira, Adilson Kleber ^[5]

Afiliação do(s) autor(es)

^[1] Mogi das Cruzes Univ UMC, Villa Lobos Campus, Sao Paulo, SP - Brazil

^[2] Butantan Inst, Lab Genet, Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Morphol & Genet Dept, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Tumor Immunol, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo de Revisão
• Fonte: OXIDATIVE MEDICINE AND CELLULAR LONGEVITY; 2017.
• Citações Web of Science: 18

Resumo

Cancer comprises a group of heterogeneous diseases encompassing high rates of morbidity and mortality. Heterogeneity, which is a hallmark of cancer, is one of the main factors related to resistance to chemotherapeutic agents leading to poor prognosis. Heterogeneity is profoundly affected by increasing levels of ROS. Under low concentrations, ROS may function as signaling molecules favoring tumorigenesis and heterogeneity, while under high ROS concentrations, these species may work as cancer modulators due to their deleterious, genotoxic or even proapoptotic effect on cancer cells. This double-edged sword effect represented by ROS relies on their ability to cause genetic and epigenetic modifications in DNA structure. Antitumor therapeutic approaches may use molecules that prevent the ROS formation precluding carcinogenesis or use chemical agents that promote a sudden increase of ROS causing considerable oxidative stress inside tumor mass. Therefore, herein, we review what ROS are and how they are produced in normal and in cancer cells while providing an argumentative discussion about their role in cancer pathophysiology. We also describe the various sources of ROS in cancer and their role in tumor heterogeneity. Further, we also discuss some therapeutic strategies from the current landscape of cancer heterogeneity, ROS modulation, or ROS production. (AU)

• Processo FAPESP: 13/07273-2 - Planejamento racional e desenvolvimento de novos protótipos derivados de fosfolipídios antitumorais como inibidores potenciais da enzima CTP: fosfoetanolamina citidililtransferase e agentes antitumorais em carcinoma de pulmão de não pequenas células
• Beneficiário: Jose Alexandre Marzagão Barbuto
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/18528-7 - Desenvolvimento de novo candidato a fármaco para o tratamento do carcinoma de pulmão de células não pequenas: CHY-1, inibidor de autofagia e protótipo de nova classe de inibidores da enzima CTP: fosfoetanolamina citidililtransferase
• Beneficiário: Adilson Kleber Ferreira
• Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores