Steroid hormones (SHs) and growth factors (GFs) bind to cell-specific receptors and regulate the complex processes of cell cycle progression, differentiation, migration and apoptosis. However, aberrations in the SH/GF signaling axis are major causative factors in the pathophysiology of human malignant disease and have the potential to cause permanent tissue-specific alterations in anatomy and physiology during some key developmental stages.
The classical biologic actions of SHs are mediated by their nuclear receptors which can act as transcriptional activators. Recent findings indicate that several protein kinases and kinase cascades are activated cooperatively by both GFs and in response to the binding of SHs to their cognate cytoplasmic or membrane-associated receptors. The available evidence further suggests that bidirectional cross-talk between several SH receptors and polypeptide GF receptor systems has critical clinical implications in tumor initiation, progression, survival, resistance to chemotherapy and patient outcomes.
GFs can modulate the expression and activity of SH receptors as well as the action of various SH receptor transcriptional co-factors in tumor cells involving, in certain circumstances, physical interaction between SH and GF receptors. The underlying molecular mechanisms are largely unknown.
SH and polypeptide GF receptors are the predominant drivers of tumor growth and progression. Despite recent advances in clarifying the mechanisms of action of SHs and GFs and their role in human cancer, it has become evident that therapies restricted to one pathway exclusively generally result in treatment failure and poor patient outcomes due to collateral pathway up-regulation. Recent findings and the results of encouraging clinical trials suggest that targeted combination chemotherapy, designed to disrupt more than one receptor-signaling pathway, may be efficient in selected patients. However, questions remain regarding the biological basis of pathway cross-talk, the mechanism of signaling cooperativity, identification of responsive patients and tumor types, selection of appropriate combined chemotherapy and the criteria for unbiased target selection in next-generation combination therapies.
This Special Issue is devoted to papers that will discuss these topics with the ultimate aim to pave the way for future therapeutic breakthroughs. The Research Topic aims to bring an update on the latest evidence regarding SHs and GFs in cancer. Reviews, and Original Research articles regarding the following sub-topics and related studies are warmly welcomed:
• Innovative aspects of SH and GF biology in human cancer;
• Dissection of SH and/or GF receptors and their activated signaling axis;
• Biological effects exerted by SHs or GFs (individually or in combination) and their receptors in cancer cells including;
- Development and mechanism of action of new small molecules and drugs that target SH and GF ligands, receptors and signaling pathways;
- Determination of the effects of SHs and GFs, and the consequences of their pathway disruption, in cancer using new approaches, such as organoids,
spheroids, exosomes, and cancer-associated fibroblasts are particularly encouraged;
- Studies of non-genomic actions of SHs, via their non-nuclear (cytoplasmic or mitochondrial) localization of their receptors;
- Cooperative transcriptional and genomic actions of SH/GF crosstalk.
- Studies on metabolic changes associated with SH and GF intercommunication in cancer.
- Studies on epigenetic changes associated with SH and/or GF action.
Steroid hormones (SHs) and growth factors (GFs) bind to cell-specific receptors and regulate the complex processes of cell cycle progression, differentiation, migration and apoptosis. However, aberrations in the SH/GF signaling axis are major causative factors in the pathophysiology of human malignant disease and have the potential to cause permanent tissue-specific alterations in anatomy and physiology during some key developmental stages.
The classical biologic actions of SHs are mediated by their nuclear receptors which can act as transcriptional activators. Recent findings indicate that several protein kinases and kinase cascades are activated cooperatively by both GFs and in response to the binding of SHs to their cognate cytoplasmic or membrane-associated receptors. The available evidence further suggests that bidirectional cross-talk between several SH receptors and polypeptide GF receptor systems has critical clinical implications in tumor initiation, progression, survival, resistance to chemotherapy and patient outcomes.
GFs can modulate the expression and activity of SH receptors as well as the action of various SH receptor transcriptional co-factors in tumor cells involving, in certain circumstances, physical interaction between SH and GF receptors. The underlying molecular mechanisms are largely unknown.
SH and polypeptide GF receptors are the predominant drivers of tumor growth and progression. Despite recent advances in clarifying the mechanisms of action of SHs and GFs and their role in human cancer, it has become evident that therapies restricted to one pathway exclusively generally result in treatment failure and poor patient outcomes due to collateral pathway up-regulation. Recent findings and the results of encouraging clinical trials suggest that targeted combination chemotherapy, designed to disrupt more than one receptor-signaling pathway, may be efficient in selected patients. However, questions remain regarding the biological basis of pathway cross-talk, the mechanism of signaling cooperativity, identification of responsive patients and tumor types, selection of appropriate combined chemotherapy and the criteria for unbiased target selection in next-generation combination therapies.
This Special Issue is devoted to papers that will discuss these topics with the ultimate aim to pave the way for future therapeutic breakthroughs. The Research Topic aims to bring an update on the latest evidence regarding SHs and GFs in cancer. Reviews, and Original Research articles regarding the following sub-topics and related studies are warmly welcomed:
• Innovative aspects of SH and GF biology in human cancer;
• Dissection of SH and/or GF receptors and their activated signaling axis;
• Biological effects exerted by SHs or GFs (individually or in combination) and their receptors in cancer cells including;
- Development and mechanism of action of new small molecules and drugs that target SH and GF ligands, receptors and signaling pathways;
- Determination of the effects of SHs and GFs, and the consequences of their pathway disruption, in cancer using new approaches, such as organoids,
spheroids, exosomes, and cancer-associated fibroblasts are particularly encouraged;
- Studies of non-genomic actions of SHs, via their non-nuclear (cytoplasmic or mitochondrial) localization of their receptors;
- Cooperative transcriptional and genomic actions of SH/GF crosstalk.
- Studies on metabolic changes associated with SH and GF intercommunication in cancer.
- Studies on epigenetic changes associated with SH and/or GF action.
