To survive various physiological and microenvironmental stresses (i.e. oxidative stress, hypoxia, nutrient deprivation, endoplasmic reticulum (ER) stress, mitochondrial stress and DNA damage), tumor cells are forced to reprogram their signaling pathways. Adaptation to stress is regulated in a spatial and temporal manner through the alteration of transcriptional, translational, and post-translational machinery. These alterations result in the clonal expansion of tumor cells with distinct gene expression and metabolic signature. Tumors’ phenotypic heterogeneity, induced as a result of stress response, drives therapy resistance, tumor relapse and metastasis.
Previous studies have demonstrated that cancer cells can exploit different strategies for adaptation and survival in adverse circumstances. For instance, in conditions of high reactive oxygen species (ROS) levels, tumor cells can alter sulfur-based metabolism, NADPH generation and the activity of antioxidant transcription factors. Under hypoxic conditions, HIF-1a upregulation leads to metabolic adaptation and promotion of angiogenesis, participates in the escape from immune recognition and increases cancer cell antioxidant capacity. During replicative stress several genes such as RAD9, PARP1, BRCA1, ATM and TP53 are modulated to maintain the genome stability and integrity. Additionally, endogenous and exogenous stresses may lead to the production of a plethora of molecules by tumor cells having either a beneficial or a harmful role in tumor progression and therapy response. However, our understanding of how cancer cells manage these stresses is far from complete. Delineation of the key mechanisms underlying stress adaptation may reveal new vulnerabilities and offer promising avenues for the development of more effective therapeutics and/or improved diagnostic tools.
The present Research Topic will highlight recent advances in the research on mechanisms of tumor cells adaptation to stressful conditions, as well as biomarkers thereof and the possible therapeutic implication of targeting these pathways.
We welcome submissions of Reviews, Mini-Reviews, Opinions, Perspectives and Original Research Articles covering, but not limited to, the following topics:
- Mechanisms supporting cancer cell survival and clonal expansion in stressful conditions, such as oxidative stress, hypoxia, ER stress, nutrient deprivation and DNA damage;
- Mechanisms driving chemo- and radiotherapy resistance, as well as resistance to target therapies and the identification of potential prognostic markers associated with these mechanisms;
- Strategies for targeting tumor adaptation to stresses (i.e identification of drugs and compounds that sensitize cancer cells to exogenous and endogenous stresses);
To survive various physiological and microenvironmental stresses (i.e. oxidative stress, hypoxia, nutrient deprivation, endoplasmic reticulum (ER) stress, mitochondrial stress and DNA damage), tumor cells are forced to reprogram their signaling pathways. Adaptation to stress is regulated in a spatial and temporal manner through the alteration of transcriptional, translational, and post-translational machinery. These alterations result in the clonal expansion of tumor cells with distinct gene expression and metabolic signature. Tumors’ phenotypic heterogeneity, induced as a result of stress response, drives therapy resistance, tumor relapse and metastasis.
Previous studies have demonstrated that cancer cells can exploit different strategies for adaptation and survival in adverse circumstances. For instance, in conditions of high reactive oxygen species (ROS) levels, tumor cells can alter sulfur-based metabolism, NADPH generation and the activity of antioxidant transcription factors. Under hypoxic conditions, HIF-1a upregulation leads to metabolic adaptation and promotion of angiogenesis, participates in the escape from immune recognition and increases cancer cell antioxidant capacity. During replicative stress several genes such as RAD9, PARP1, BRCA1, ATM and TP53 are modulated to maintain the genome stability and integrity. Additionally, endogenous and exogenous stresses may lead to the production of a plethora of molecules by tumor cells having either a beneficial or a harmful role in tumor progression and therapy response. However, our understanding of how cancer cells manage these stresses is far from complete. Delineation of the key mechanisms underlying stress adaptation may reveal new vulnerabilities and offer promising avenues for the development of more effective therapeutics and/or improved diagnostic tools.
The present Research Topic will highlight recent advances in the research on mechanisms of tumor cells adaptation to stressful conditions, as well as biomarkers thereof and the possible therapeutic implication of targeting these pathways.
We welcome submissions of Reviews, Mini-Reviews, Opinions, Perspectives and Original Research Articles covering, but not limited to, the following topics:
- Mechanisms supporting cancer cell survival and clonal expansion in stressful conditions, such as oxidative stress, hypoxia, ER stress, nutrient deprivation and DNA damage;
- Mechanisms driving chemo- and radiotherapy resistance, as well as resistance to target therapies and the identification of potential prognostic markers associated with these mechanisms;
- Strategies for targeting tumor adaptation to stresses (i.e identification of drugs and compounds that sensitize cancer cells to exogenous and endogenous stresses);
