In most cases, cancer develops as a result of non-inheritable somatic mutations (epimutations), acquired by the individual adult cell, during the evolution of the cell, and propagated into an expanding clone of progen...In most cases, cancer develops as a result of non-inheritable somatic mutations (epimutations), acquired by the individual adult cell, during the evolution of the cell, and propagated into an expanding clone of progeny of the cells by natural selection [1]. The role of microenvironment in selection for such acquired mutations, or epimutations, is a focus of scientific research in carcinogenesis [2]. Here we describe a defective DNA response to hypoxia due to epigenetic aberrancies, in cancer cellular biology [3]. We also summarize a literature review on hypoxia mediated epigenetic responses, and its role in carcinogenesis and metastasis. Further, we review a novel method of treating hypoxic solid tumors with a combination of epigenetic modifiers with both in vitro and in vivo results in human, translating to an improved prognosis and clinical outcome. We propose that this approach both independently and synergistically (with the current standard of care) can provide an improved outcome.展开更多
This article discusses the role of epithelial mesenchymal transition (EMT) and addresses the scientific merits on epigenetic regulation of EMT. The importance of EMT as a prognostic biomarker is explored and the ratio...This article discusses the role of epithelial mesenchymal transition (EMT) and addresses the scientific merits on epigenetic regulation of EMT. The importance of EMT as a prognostic biomarker is explored and the rationale on application of multitargeted epigenetic therapy is discussed. We describe a literature review of the epigenetic influence of such process and we present a potentially effective method to reverse the epigenetic switch in favor for MET, in a clinical setting. A case series of advanced solid tumors are summarized aiming at generating hypothesis for the future recommendations for clinical trials targeting the tumor’s biological behavior through inhibition of EMT. Hypothesis: We propose an integral and integrative approach that can modify tumor’s biological behavior through inhibition of EMT, and further reduce the chances of metastasis, that can translate to improved outcome and patient’s survival in advanced disease.展开更多
文摘In most cases, cancer develops as a result of non-inheritable somatic mutations (epimutations), acquired by the individual adult cell, during the evolution of the cell, and propagated into an expanding clone of progeny of the cells by natural selection [1]. The role of microenvironment in selection for such acquired mutations, or epimutations, is a focus of scientific research in carcinogenesis [2]. Here we describe a defective DNA response to hypoxia due to epigenetic aberrancies, in cancer cellular biology [3]. We also summarize a literature review on hypoxia mediated epigenetic responses, and its role in carcinogenesis and metastasis. Further, we review a novel method of treating hypoxic solid tumors with a combination of epigenetic modifiers with both in vitro and in vivo results in human, translating to an improved prognosis and clinical outcome. We propose that this approach both independently and synergistically (with the current standard of care) can provide an improved outcome.
文摘This article discusses the role of epithelial mesenchymal transition (EMT) and addresses the scientific merits on epigenetic regulation of EMT. The importance of EMT as a prognostic biomarker is explored and the rationale on application of multitargeted epigenetic therapy is discussed. We describe a literature review of the epigenetic influence of such process and we present a potentially effective method to reverse the epigenetic switch in favor for MET, in a clinical setting. A case series of advanced solid tumors are summarized aiming at generating hypothesis for the future recommendations for clinical trials targeting the tumor’s biological behavior through inhibition of EMT. Hypothesis: We propose an integral and integrative approach that can modify tumor’s biological behavior through inhibition of EMT, and further reduce the chances of metastasis, that can translate to improved outcome and patient’s survival in advanced disease.
