Treatment of patients with severe COVID-19, is challenging specifically when a patient carries high risk of mortality, such as old age, immune suppression or cancer. Also a patient who manifests the disease with sever...Treatment of patients with severe COVID-19, is challenging specifically when a patient carries high risk of mortality, such as old age, immune suppression or cancer. Also a patient who manifests the disease with severe symptoms, such as hypoxia, requiring supplemental oxygenation, or artificial ventilation has a poor prognosis. Here we review the scientific rationale used to design a very promising therapy based on existing literature, but in significantly different method and protocols, used to treat cases of severe COVID-19, and we conclude that although the effort on drug development has been enormous, but as of today, we do not have a therapy with specific characteristics as this protocol, to be used safely in human and yet potentially meet the expectations we would have for a so called “effective therapy”. Further clinical trials are needed to support this hypothesis and generate further hypothesis to prove the concept in larger cohort of patients.展开更多
Since the discovery of tyrosine kinase inhibitors in treatment of lung cancer harboring such actionable targets, many lives have been prolonged. To the same extent, same group of patients have failed to benefit from t...Since the discovery of tyrosine kinase inhibitors in treatment of lung cancer harboring such actionable targets, many lives have been prolonged. To the same extent, same group of patients have failed to benefit from this category of drugs, in long run, either initially or during the course of treatments, simply due to either known or unknown mechanism of resistance which occurs very often in the first few months after initiation of therapy. The resistance is 100 percent expected, and no patient is reported to be a waiver of such pattern. With best practices of oncology, the average duration of response is expected to be below 12 months [1]. About half of the resistance is caused by mutation at T790M in EGFR target, which can be revealed by liquid biopsy [1] [2]. The most recent studies have revealed the significant role of epigenome in controlling this complicated resistance pattern. We have learned that Histone deacetylation, as opposed to promoter methylation, may contribute to the epigenetic silencing and to EGFR TKI resistance in NSCLC [3] [4]. Here we present a case study with a model of combinational therapy that targets the EGFR molecule, (by small molecule inhibitor, Afatanib) with simultaneous epigenetic modification of the target, (by application of multitargeted epigenetic therapy (MTET) with significantly improved clinical results. We propose further trials are needed to support such hypothesis, which if proved, could significantly shift the current practices in management of this set of cases in lung adenocarcinomas.展开更多
文摘Treatment of patients with severe COVID-19, is challenging specifically when a patient carries high risk of mortality, such as old age, immune suppression or cancer. Also a patient who manifests the disease with severe symptoms, such as hypoxia, requiring supplemental oxygenation, or artificial ventilation has a poor prognosis. Here we review the scientific rationale used to design a very promising therapy based on existing literature, but in significantly different method and protocols, used to treat cases of severe COVID-19, and we conclude that although the effort on drug development has been enormous, but as of today, we do not have a therapy with specific characteristics as this protocol, to be used safely in human and yet potentially meet the expectations we would have for a so called “effective therapy”. Further clinical trials are needed to support this hypothesis and generate further hypothesis to prove the concept in larger cohort of patients.
文摘Since the discovery of tyrosine kinase inhibitors in treatment of lung cancer harboring such actionable targets, many lives have been prolonged. To the same extent, same group of patients have failed to benefit from this category of drugs, in long run, either initially or during the course of treatments, simply due to either known or unknown mechanism of resistance which occurs very often in the first few months after initiation of therapy. The resistance is 100 percent expected, and no patient is reported to be a waiver of such pattern. With best practices of oncology, the average duration of response is expected to be below 12 months [1]. About half of the resistance is caused by mutation at T790M in EGFR target, which can be revealed by liquid biopsy [1] [2]. The most recent studies have revealed the significant role of epigenome in controlling this complicated resistance pattern. We have learned that Histone deacetylation, as opposed to promoter methylation, may contribute to the epigenetic silencing and to EGFR TKI resistance in NSCLC [3] [4]. Here we present a case study with a model of combinational therapy that targets the EGFR molecule, (by small molecule inhibitor, Afatanib) with simultaneous epigenetic modification of the target, (by application of multitargeted epigenetic therapy (MTET) with significantly improved clinical results. We propose further trials are needed to support such hypothesis, which if proved, could significantly shift the current practices in management of this set of cases in lung adenocarcinomas.
