Title:Oxidative Stress, Redox Signaling and Cancer Chemoresistance: Putting Together the Pieces of the Puzzle
Volume: 21
Issue: 28
Author(s): Vanessa Jacob Victorino, Luciana Pizzatti, Pamela Michelletti and Carolina Panis
Affiliation:
关键词:
抗肿瘤药物,癌症,化疗耐药性,化疗,氧化应激,氧化还原内稳态。
摘要: Chemotherapy continues to be the main treatment option for cancer. Although systemic chemotherapy can efficiently
eradicate cancer cells, a significant proportion of patients carry tumors that present a chemoresistant phenotype, resulting
in disease progression, cancer relapse, and reduced survival. It has also become clear that the effect of most chemotherapeutic
drugs is associated with their capacity to generate reactive species (RS) that bind to specific structures
within the cancer cell and promote cell death. Due to repeated exposure to chemotherapeutic agents, the redox homeostasis
of cancer cells is continuously disturbed, which can result in changes to the cell’s ability to cope with excessive RS
levels through the production of protective molecules. It is thought that the imbalance resulting from this process—
oxidative stress—is toxic to cancer cells. Paradoxically, the metabolites produced during oxidative stress can favor the
survival of some cancer subpopulations, which present specific gene signatures that confer a chemoresistant phenotype on
these clones. Despite the huge amount of information generated by currently available technologies, we cannot predict
whether this resistance will arise during chemotherapy and we still do not fully understand the mechanism by which it
arises. In this review, we discuss the main findings regarding the role of oxidative stress signaling in cancer chemotherapy
and the key redox molecules and pathways that lead to the development of chemoresistance.