Research Topic

Targeting Intra- and Extracellular signals contributing to Cancer Stemness and Metastasis in aggressive cancers

About this Research Topic

Cancer-related diseases are within the top three causes of death worldwide. Although for some cancer types the survival rate has greatly improved during the last years due to advances in diagnostic and therapeutic approaches, several highly aggressive cancers remain as unmet clinical needs. These aggressive tumors share common features such as high chemoresistance to conventional systemic therapies, rapid relapse after treatment and metastases formation in vital organs which, eventually, leads to death. These features are often attributed to specific subpopulations of malignant cells with tumor- and metastasis-initiating properties, such as cancer stem cells (CSCs). Indeed, it has become apparent that cancer cells within a tumor are very heterogeneous: not only genetic and epigenetically, but also in terms of differentiation state and functionality. Numerous microenvironmental and cell-autonomous factors support and amplify such heterogeneity, contributing to cancer malignancy by inducing stemness and the acquisition of pro-metastatic abilities.

Due to its crucial role in chemoresistance, tumor relapse and metastasis, a great number of research projects are currently underway trying to find and target both external and internal signals regulating the functionality of cancer and metastasis-initiating cells. Due to its intrinsic similarities with normal adult stem cells, the scientific community from the cancer stemness and metastasis field faces a great challenge: the identification or design of therapeutic strategies able to specifically target tumoral stem cells maintaining the normal stem cells pool unharmed. To do so, the study of the tumor microenvironment (or CSC niche specifically affecting these cells), has become an essential tool due to its particularities: on one side, the fundamental properties of certain tumors, such as hypoxia and lack of nutrients due to the hypervascularization and desmoplasia; on the other side, the unique features conferred by tumoral stromal cells, including endothelial cells and different populations of fibroblasts and immune cells. Apart from that, we now know that CSC may present specific functional properties, such as their unique metabolism, that makes them essentially different from normal stem cells and represent excellent potential targets.

For this Research Topic, we invite authors to submit original contributions that provide novel findings in the field of therapeutic approaches targeting cancer stemness and metastasis, with special focus in highly aggressive cancers such as glioblastoma, colon cancer and pancreatic cancer. In particular (but not limited to), insights in the areas of therapeutic targeting of intracellular signals (metabolites, calcium, reactive oxygen species, cellular stress including oxidative stress, organelle functionality) or extracellular signals (soluble factors such as growth factors, ligands or metabolites, as well as extracellular matrix and stromal cells). Reviews that highlight new findings in the above areas are also welcome.


Keywords: Tumor stemness, metastasis, microenvironment, metabolism, therapeutic targeting


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Cancer-related diseases are within the top three causes of death worldwide. Although for some cancer types the survival rate has greatly improved during the last years due to advances in diagnostic and therapeutic approaches, several highly aggressive cancers remain as unmet clinical needs. These aggressive tumors share common features such as high chemoresistance to conventional systemic therapies, rapid relapse after treatment and metastases formation in vital organs which, eventually, leads to death. These features are often attributed to specific subpopulations of malignant cells with tumor- and metastasis-initiating properties, such as cancer stem cells (CSCs). Indeed, it has become apparent that cancer cells within a tumor are very heterogeneous: not only genetic and epigenetically, but also in terms of differentiation state and functionality. Numerous microenvironmental and cell-autonomous factors support and amplify such heterogeneity, contributing to cancer malignancy by inducing stemness and the acquisition of pro-metastatic abilities.

Due to its crucial role in chemoresistance, tumor relapse and metastasis, a great number of research projects are currently underway trying to find and target both external and internal signals regulating the functionality of cancer and metastasis-initiating cells. Due to its intrinsic similarities with normal adult stem cells, the scientific community from the cancer stemness and metastasis field faces a great challenge: the identification or design of therapeutic strategies able to specifically target tumoral stem cells maintaining the normal stem cells pool unharmed. To do so, the study of the tumor microenvironment (or CSC niche specifically affecting these cells), has become an essential tool due to its particularities: on one side, the fundamental properties of certain tumors, such as hypoxia and lack of nutrients due to the hypervascularization and desmoplasia; on the other side, the unique features conferred by tumoral stromal cells, including endothelial cells and different populations of fibroblasts and immune cells. Apart from that, we now know that CSC may present specific functional properties, such as their unique metabolism, that makes them essentially different from normal stem cells and represent excellent potential targets.

For this Research Topic, we invite authors to submit original contributions that provide novel findings in the field of therapeutic approaches targeting cancer stemness and metastasis, with special focus in highly aggressive cancers such as glioblastoma, colon cancer and pancreatic cancer. In particular (but not limited to), insights in the areas of therapeutic targeting of intracellular signals (metabolites, calcium, reactive oxygen species, cellular stress including oxidative stress, organelle functionality) or extracellular signals (soluble factors such as growth factors, ligands or metabolites, as well as extracellular matrix and stromal cells). Reviews that highlight new findings in the above areas are also welcome.


Keywords: Tumor stemness, metastasis, microenvironment, metabolism, therapeutic targeting


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

29 December 2020 Abstract
28 April 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

29 December 2020 Abstract
28 April 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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