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
Existing literature supports the role of signaling protein vascular endothelial growth factor (VEGF) in tumor growth and metastasis and furthers its involvement in recurrence. In both experimental and clinical studies...Existing literature supports the role of signaling protein vascular endothelial growth factor (VEGF) in tumor growth and metastasis and furthers its involvement in recurrence. In both experimental and clinical studies, VEGF has been shown to be a significant factor involved for aberrant blood vessel growth, and in fact is the target of several classes of antineoplastic drugs [1] [2] [3] [4]. That said, the current standard of care for estrogen receptor positive breast cancer (although improved over the last decade), has not provided a “meaningful preventive shift” since the discovery of angiogenesis and its role in induction of recurrence. In this article, we discuss an anti angiogenic therapy implementing natural compounds to inhibit the production of VEGF. We applied our preclinical data to justify the predicted effect on VEGF. We used liquid biopsy to monitor patients response to therapy as a surrogate for recurrence. We hypothesize that by inhibition of angiogenesis through this protocol, we are able to positively impact tumor recurrence. It is our experience that patients in our sample even with high recurrence scores (based on Oncotype Dx testing) had a major reduction in recurrence when estrogen blockers were combined with this protocol. We also propose longitudinal studies to compare outcomes with combinational therapies with estrogen blockers in highly expected to recur disease.展开更多
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
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.
文摘Existing literature supports the role of signaling protein vascular endothelial growth factor (VEGF) in tumor growth and metastasis and furthers its involvement in recurrence. In both experimental and clinical studies, VEGF has been shown to be a significant factor involved for aberrant blood vessel growth, and in fact is the target of several classes of antineoplastic drugs [1] [2] [3] [4]. That said, the current standard of care for estrogen receptor positive breast cancer (although improved over the last decade), has not provided a “meaningful preventive shift” since the discovery of angiogenesis and its role in induction of recurrence. In this article, we discuss an anti angiogenic therapy implementing natural compounds to inhibit the production of VEGF. We applied our preclinical data to justify the predicted effect on VEGF. We used liquid biopsy to monitor patients response to therapy as a surrogate for recurrence. We hypothesize that by inhibition of angiogenesis through this protocol, we are able to positively impact tumor recurrence. It is our experience that patients in our sample even with high recurrence scores (based on Oncotype Dx testing) had a major reduction in recurrence when estrogen blockers were combined with this protocol. We also propose longitudinal studies to compare outcomes with combinational therapies with estrogen blockers in highly expected to recur disease.
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.
