The development of therapeutic resistance to anticancer agents, such as cytotoxic molecules and targeted therapies, is one of the major challenges in cancer treatment. Therapeutic resistance is a complex process that arises from many factors. In particular, oncogene activating, and tumor suppressor inactivating mutations, either pre-existing (intrinsic resistance) or induced by drugs (acquired resistance), can mediate resistance to certain agents and promote tumor cell evasion from apoptosis, cell cycle arrest, immune suppression and other mechanisms that lead to therapeutic failure. There remains an urgent need to improve our understanding of the genetic and epigenetic basis for resistance to chemotherapeutics in tumor cells and within the tumor microenvironment.
In this special issue, we call for research papers (basic, translational, and clinical), perspectives, reviews and protocols evaluating therapeutic resistance in cancer, specifically regarding genetic and epigenetic mechanisms related to altered gene expression and novel mutations in tumor and stromal cells that can impact key processes involved in chemoresistance, such as EMT, TEM, metabolism, and immune invasion. Utilization of cutting-edge sequencing technologies, tumor models which can mimic tumor/stromal interaction (e.g., 3D organotypic models), and models of tumor/immune cell interactions can further delineate the contribution of gene expression and mutations on these signaling processes that promote tumor cell survival and progression. In addition to basic and translational approaches, bioinformatic analysis of clinical datasets (those that include a training dataset and at least one dataset for external validation) are also strongly encouraged for submission to give insight into novel mechanisms to evaluate experimentally. The new knowledge and prospects herein will enable us to better understand the complex pathways of therapeutic resistance and overcome this obstacle to improve patient care.
Advances in novel sequencing approaches from bulk tissue, single cells, micro-dissected cells, co-culture systems and complex 3D organotypic models have shed light into genetic and epigenetic modulation of tumor cell resistance mechanisms. Coupled with the increasing understanding of the complex relationship between cancer cells and their tumor microenvironment, alterations in gene expression as well as increased mutational burden arising from disease progression (i.e., from genomic instability) and in response to chemotherapeutic intervention may alter tumor and stromal cell behavior that promotes resistance to standard therapeutic practices. Within the tumor microenvironment, these genetic/epigenetic alterations can improve the ability of tumor cells to exploit signaling molecules and metabolites from stromal cells (e.g., fibroblasts, adipocytes) as well as enable them to avoid detection and elimination from immune cells. Changes to the genetic landscape can also directly confer resistance to the cytotoxic effect of targeted small molecules through modulating signaling pathways required for the efficacy of these agents. Elucidating these potential (epi)genetic mechanisms may inform therapeutic approaches to delay or overcome resistance and improve patient outcomes.
The development of therapeutic resistance to anticancer agents, such as cytotoxic molecules and targeted therapies, is one of the major challenges in cancer treatment. Therapeutic resistance is a complex process that arises from many factors. In particular, oncogene activating, and tumor suppressor inactivating mutations, either pre-existing (intrinsic resistance) or induced by drugs (acquired resistance), can mediate resistance to certain agents and promote tumor cell evasion from apoptosis, cell cycle arrest, immune suppression and other mechanisms that lead to therapeutic failure. There remains an urgent need to improve our understanding of the genetic and epigenetic basis for resistance to chemotherapeutics in tumor cells and within the tumor microenvironment.
In this special issue, we call for research papers (basic, translational, and clinical), perspectives, reviews and protocols evaluating therapeutic resistance in cancer, specifically regarding genetic and epigenetic mechanisms related to altered gene expression and novel mutations in tumor and stromal cells that can impact key processes involved in chemoresistance, such as EMT, TEM, metabolism, and immune invasion. Utilization of cutting-edge sequencing technologies, tumor models which can mimic tumor/stromal interaction (e.g., 3D organotypic models), and models of tumor/immune cell interactions can further delineate the contribution of gene expression and mutations on these signaling processes that promote tumor cell survival and progression. In addition to basic and translational approaches, bioinformatic analysis of clinical datasets (those that include a training dataset and at least one dataset for external validation) are also strongly encouraged for submission to give insight into novel mechanisms to evaluate experimentally. The new knowledge and prospects herein will enable us to better understand the complex pathways of therapeutic resistance and overcome this obstacle to improve patient care.
Advances in novel sequencing approaches from bulk tissue, single cells, micro-dissected cells, co-culture systems and complex 3D organotypic models have shed light into genetic and epigenetic modulation of tumor cell resistance mechanisms. Coupled with the increasing understanding of the complex relationship between cancer cells and their tumor microenvironment, alterations in gene expression as well as increased mutational burden arising from disease progression (i.e., from genomic instability) and in response to chemotherapeutic intervention may alter tumor and stromal cell behavior that promotes resistance to standard therapeutic practices. Within the tumor microenvironment, these genetic/epigenetic alterations can improve the ability of tumor cells to exploit signaling molecules and metabolites from stromal cells (e.g., fibroblasts, adipocytes) as well as enable them to avoid detection and elimination from immune cells. Changes to the genetic landscape can also directly confer resistance to the cytotoxic effect of targeted small molecules through modulating signaling pathways required for the efficacy of these agents. Elucidating these potential (epi)genetic mechanisms may inform therapeutic approaches to delay or overcome resistance and improve patient outcomes.