ABSTRACT
The National Cancer Institute (NCI) Division of Cancer Prevention (DCP) convened the “Translational Advances in Cancer Prevention Agent Development (TACPAD) Workshop on Immunomodulatory Agents” as a virtual 2-day workshop on September 13 to 14, 2021. The main goals of this workshop were to foster the exchange of ideas and potentially new collaborative interactions among leading cancer immunoprevention researchers from basic and clinical research and highlight new and emerging trends in immunoprevention. The workshop included an overview of the mechanistic classes of immunomodulatory agents and three sessions covering the gamut from preclinical to clinical studies. The workshop convened individuals working in immunology and cancer prevention to discuss trends in discovery and development of immunomodulatory agents individually and in combination with other chemopreventive agents or vaccines.
ABSTRACT
The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.
ABSTRACT
The Division of Cancer Prevention of the National Cancer Institute (NCI) and the Office of Disease Prevention of the National Institutes of Health co-sponsored the Translational Advances in Cancer Prevention Agent Development Meeting on August 27 to 28, 2020. The goals of this meeting were to foster the exchange of ideas and stimulate new collaborative interactions among leading cancer prevention researchers from basic and clinical research; highlight new and emerging trends in immunoprevention and chemoprevention as well as new information from clinical trials; and provide information to the extramural research community on the significant resources available from the NCI to promote prevention agent development and rapid translation to clinical trials. The meeting included two plenary talks and five sessions covering the range from pre-clinical studies with chemo/immunopreventive agents to ongoing cancer prevention clinical trials. In addition, two NCI informational sessions describing contract resources for the preclinical agent development and cooperative grants for the Cancer Prevention Clinical Trials Network were also presented.
ABSTRACT
Natural compounds from diverse sources, including botanicals and commonly consumed foods and beverages, exert beneficial health effects via mechanisms that impact the epigenome and gene expression during disease pathogenesis. By targeting the socalled epigenetic ‘readers’, ‘writers’, and ‘erasers’, dietary phytochemicals can reverse abnormal epigenome signatures in cancer cells and preneoplastic stages. Thus, such agents provide avenues for cancer interception via prevention or treatment/therapeutic strategies. To date, much of the focus on dietary agents has been directed towards writers (e.g., histone acetyltransferases) and erasers (e.g., histone deacetylases), with less attention given to epigenetic readers (e.g., BRD proteins). The drug JQ1 was developed as a prototype epigenetic reader inhibitor, selectively targeting members of the bromodomain and extraterminal domain (BET) family, such as BRD4. Clinical trials with JQ1 as a single agent, or in combination with standard of care therapy, revealed antitumor efficacy but not without toxicity or resistance. In pursuit of second-generation epigenetic reader inhibitors, attention has shifted to natural sources, including dietary agents that might be repurposed as ‘JQ1-like’ bioactives. This review summarizes the current status of nascent research activity focused on natural compounds as inhibitors of BET and other epigenetic ‘reader’ proteins, with a perspective on future directions and opportunities.
ABSTRACT
Natural compounds from diverse sources, including botanicals and commonly consumed foods and beverages, exert beneficial health effects via mechanisms that impact the epigenome and gene expression during disease pathogenesis. By targeting the socalled epigenetic ‘readers’, ‘writers’, and ‘erasers’, dietary phytochemicals can reverse abnormal epigenome signatures in cancer cells and preneoplastic stages. Thus, such agents provide avenues for cancer interception via prevention or treatment/therapeutic strategies. To date, much of the focus on dietary agents has been directed towards writers (e.g., histone acetyltransferases) and erasers (e.g., histone deacetylases), with less attention given to epigenetic readers (e.g., BRD proteins). The drug JQ1 was developed as a prototype epigenetic reader inhibitor, selectively targeting members of the bromodomain and extraterminal domain (BET) family, such as BRD4. Clinical trials with JQ1 as a single agent, or in combination with standard of care therapy, revealed antitumor efficacy but not without toxicity or resistance. In pursuit of second-generation epigenetic reader inhibitors, attention has shifted to natural sources, including dietary agents that might be repurposed as ‘JQ1-like’ bioactives. This review summarizes the current status of nascent research activity focused on natural compounds as inhibitors of BET and other epigenetic ‘reader’ proteins, with a perspective on future directions and opportunities.