One of the biggest barriers to cure cancer is the occurrence of metastasis. Metastatic cells are characterized by having a high mutational load in their DNA as well as many other epigenetic modifications compared to the primary tumor cells from which they derive. In addition, they are generally resistant to conventional radio- and chemotherapy. Therapy-resistance in cancer is provoked by a myriad of factors that together favor a drastic evolution of tumors into particularly aggressive variants that do not respond to chemotherapeutic regimens. The main factors that contribute to such resistance are metabolic changes, hypoxic microenvironment, epigenetic/genetic modulation, aberrant inflammatory response, autophagy disruption and evasion from apoptosis. These events are interlinked, for example, both metabolic changes and hypoxia contribute to the angiogenic development of cancer.
Despite the fact that the altered metabolic pathways in cancer cells were first described almost a century ago, the connection between these alterations and other crucial cellular mechanisms that determine cancer evolution is still poorly understood. For example, while a hypoxic environment directly promotes radio- and chemoresistance in tumor cells; hypoxia-associated microenvironmental stress modulates tumor cell metabolism, survival, and angiogenesis.
The purpose of this Research Topic is to describe key metabolic and tumor microenvironment changes required for a malignant cell (derived from the primary tumor) to become metastatic (and generally resistant to chemo & radiotherapy). Understanding how these factors interact with each other and what are the determinant proteins ultimately responsible for resistance will open new avenues for cancer treatment and therapy.
In this Research Topic we welcome Original Research, Review and Mini-Review articles focussing on the following subtopics:
1) Metabolites resulting from glycolysis, gluconeogenesis, and cellular respiration.
2) Antioxidant defense and cancer: implications for reactive oxygen species (ROS) regulation.
3) Cancer-associated fibroblasts (CAFs) and inflammation: role of tumor microenvironment in inducing drug resistance.
4) Hypoxic adaptation to different niches, including the cancer stem cell niche.
5) Glycolysis in cancer, in the specific context of metabolic plasticity, which may be specifically associated with resistance to therapy and metastasis.
6) Examples of alternative splicing and RNA translation in tumor progression.
7) How does lipid metabolic adaptation play a crucial role in cancer?
8) Disruption of mitochondrial function and mitochondrial DNA mutations in relation to the development and progression of cancer.
9) Targeting aberrant signaling pathways related to stemness.
10) Autophagy and apoptosis: How does the disruption of autophagy influence and determine the resistance acquisition phenotype, and how do these two processes are interconnected.
11) Vasculogenesis and angiogenesis: Advances in how these two closely related processes predispose to metastasis.
12) How the metabolism in cancer interacts with the microbiome.
13) Where the new therapies in oncology are headed: An overview.
One of the biggest barriers to cure cancer is the occurrence of metastasis. Metastatic cells are characterized by having a high mutational load in their DNA as well as many other epigenetic modifications compared to the primary tumor cells from which they derive. In addition, they are generally resistant to conventional radio- and chemotherapy. Therapy-resistance in cancer is provoked by a myriad of factors that together favor a drastic evolution of tumors into particularly aggressive variants that do not respond to chemotherapeutic regimens. The main factors that contribute to such resistance are metabolic changes, hypoxic microenvironment, epigenetic/genetic modulation, aberrant inflammatory response, autophagy disruption and evasion from apoptosis. These events are interlinked, for example, both metabolic changes and hypoxia contribute to the angiogenic development of cancer.
Despite the fact that the altered metabolic pathways in cancer cells were first described almost a century ago, the connection between these alterations and other crucial cellular mechanisms that determine cancer evolution is still poorly understood. For example, while a hypoxic environment directly promotes radio- and chemoresistance in tumor cells; hypoxia-associated microenvironmental stress modulates tumor cell metabolism, survival, and angiogenesis.
The purpose of this Research Topic is to describe key metabolic and tumor microenvironment changes required for a malignant cell (derived from the primary tumor) to become metastatic (and generally resistant to chemo & radiotherapy). Understanding how these factors interact with each other and what are the determinant proteins ultimately responsible for resistance will open new avenues for cancer treatment and therapy.
In this Research Topic we welcome Original Research, Review and Mini-Review articles focussing on the following subtopics:
1) Metabolites resulting from glycolysis, gluconeogenesis, and cellular respiration.
2) Antioxidant defense and cancer: implications for reactive oxygen species (ROS) regulation.
3) Cancer-associated fibroblasts (CAFs) and inflammation: role of tumor microenvironment in inducing drug resistance.
4) Hypoxic adaptation to different niches, including the cancer stem cell niche.
5) Glycolysis in cancer, in the specific context of metabolic plasticity, which may be specifically associated with resistance to therapy and metastasis.
6) Examples of alternative splicing and RNA translation in tumor progression.
7) How does lipid metabolic adaptation play a crucial role in cancer?
8) Disruption of mitochondrial function and mitochondrial DNA mutations in relation to the development and progression of cancer.
9) Targeting aberrant signaling pathways related to stemness.
10) Autophagy and apoptosis: How does the disruption of autophagy influence and determine the resistance acquisition phenotype, and how do these two processes are interconnected.
11) Vasculogenesis and angiogenesis: Advances in how these two closely related processes predispose to metastasis.
12) How the metabolism in cancer interacts with the microbiome.
13) Where the new therapies in oncology are headed: An overview.