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    Exercise, Diet, and Weight Management During Cancer Treatment: ASCO Guideline. Journal of clinical oncology : official journal of the American Society of Clinical Oncology PURPOSE:To provide guidance on exercise, diet, and weight management during active cancer treatment in adults. METHODS:A systematic review of the literature identified systematic reviews and randomized controlled trials evaluating the impact of aerobic and resistance exercise, specific diets and foods, and intentional weight loss and avoidance of weight gain in adults during cancer treatment, on quality of life, treatment toxicity, and cancer control. PubMed and the Cochrane Library were searched from January 2000 to May 2021. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS:The evidence base consisted of 52 systematic reviews (42 for exercise, nine for diet, and one for weight management), and an additional 23 randomized controlled trials. The most commonly studied types of cancer were breast, prostate, lung, and colorectal. Exercise during cancer treatment led to improvements in cardiorespiratory fitness, strength, fatigue, and other patient-reported outcomes. Preoperative exercise in patients with lung cancer led to a reduction in postoperative length of hospital stay and complications. Neutropenic diets did not decrease risk of infection during cancer treatment. RECOMMENDATIONS:Oncology providers should recommend regular aerobic and resistance exercise during active treatment with curative intent and may recommend preoperative exercise for patients undergoing surgery for lung cancer. Neutropenic diets are not recommended to prevent infection in patients with cancer during active treatment. Evidence for other dietary and weight loss interventions during cancer treatment was very limited. The guideline discusses special considerations, such as exercise in individuals with advanced cancer, and highlights the critical need for more research in this area, particularly regarding diet and weight loss interventions during cancer treatment.Additional information is available at www.asco.org/supportive-care-guidelines. 10.1200/JCO.22.00687
    Cancer cells depend on environmental lipids for proliferation when electron acceptors are limited. Nature metabolism Production of oxidized biomass, which requires regeneration of the cofactor NAD, can be a proliferation bottleneck that is influenced by environmental conditions. However, a comprehensive quantitative understanding of metabolic processes that may be affected by NAD deficiency is currently missing. Here, we show that de novo lipid biosynthesis can impose a substantial NAD consumption cost in proliferating cancer cells. When electron acceptors are limited, environmental lipids become crucial for proliferation because NAD is required to generate precursors for fatty acid biosynthesis. We find that both oxidative and even net reductive pathways for lipogenic citrate synthesis are gated by reactions that depend on NAD availability. We also show that access to acetate can relieve lipid auxotrophy by bypassing the NAD consuming reactions. Gene expression analysis demonstrates that lipid biosynthesis strongly anti-correlates with expression of hypoxia markers across tumor types. Overall, our results define a requirement for oxidative metabolism to support biosynthetic reactions and provide a mechanistic explanation for cancer cell dependence on lipid uptake in electron acceptor-limited conditions, such as hypoxia. 10.1038/s42255-022-00588-8
    IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer. Felices M,Chu S,Kodal B,Bendzick L,Ryan C,Lenvik A J,Boylan K L M,Wong H C,Skubitz A P N,Miller J S,Geller M A Gynecologic oncology OBJECTIVE:Natural killer (NK) cells represent a powerful immunotherapeutic target as they lyse tumors directly, do not require differentiation, and can elicit potent inflammatory responses. The objective of these studies was to use an IL-15 super-agonist complex, ALT-803 (Altor BioScience Corporation), to enhance the function of both normal and ovarian cancer patient derived NK cells by increasing cytotoxicity and cytokine production. METHODS:NK cell function from normal donor peripheral blood mononuclear cells (PBMCs) and ovarian cancer patient ascites was assessed using flow cytometry and chromium release assays ±ALT-803 stimulation. To evaluate the ability of ALT-803 to enhance NK cell function in vivo against ovarian cancer, we used a MA148-luc ovarian cancer NOD scid gamma (NSG) xenogeneic mouse model with transferred human NK cells. RESULTS:ALT-803 potently enhanced functionality of NK cells against all ovarian cancer cell lines with significant increases seen in CD107a, IFNγ and TNFα expression depending on target cell line. Function was also rescued in NK cells derived from ovarian cancer patient ascites. Finally, only animals treated with intraperitoneal ALT-803 displayed an NK dependent significant decrease in tumor. CONCLUSIONS:ALT-803 enhances NK cell cytotoxicity against ovarian cancer in vitro and in vivo and is able to rescue functionality of NK cells derived from ovarian cancer patient ascites. These findings suggest that ALT-803 has the potential to enhance NK cell-based immunotherapeutic approaches for the treatment of ovarian cancer. 10.1016/j.ygyno.2017.02.028
    [Research progress in mechanism of berberine's antitumor action]. Yang Xian-Hao,Zhang Li-Jin,Luo Meng-Jun,Luo Shuai,Gong Yu-Yuan,Chen Tao Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica Malignant tumor, an important factor threatening human life and health, brings huge economic burden to patients. At present, chemoradiotherapy is still the main treatment method for tumor diseases, but there are also great side effects when it plays a therapeutic role. Traditional Chinese medicine in the prevention and treatment of tumor diseases has many advantages such as few side effects, improving the physiological state of patients, and slowing down the side effects of radiotherapy and chemotherapy. Berberine is an effective component of rhizoma coptidis, with a very good antitumor effect. It can inhibit tumor cell proliferation, promote tumor cell apoptosis, inhibit tumor metastasis and angiogenesis, regulate tumor autophagy, reverse multi-drug resistance of tumor, regulate the body immunity, and affect tumor metabolic reprogramming to play its role. Compared with chemical preparations, berberine has a wide range of sources, with high safety and easy access, and has great potential in the prevention and treatment of malignant tumors. In this article, we would mainly review the research progress on the antitumor mechanism of berberine in recent years. 10.19540/j.cnki.cjcmm.20210209.601
    Anticancer Drugs Approved by the US Food and Drug Administration From 2009 to 2020 According to Their Mechanism of Action. Olivier Timothée,Haslam Alyson,Prasad Vinay JAMA network open Importance:Both novel and next-in-class cancer drugs have a role in oncology, but the relative development of each is understudied. Objective:To characterize the mechanisms of action of anticancer drugs approved by the US Food and Drug Administration (FDA) between 2009 and 2020, noting how many approvals were based on a new mechanism of action vs next-in-class approvals. Design, Study, and Participants:This cross-sectional study included all anticancer drugs approved by the FDA from January 2009 to December 2020. The mechanism of action of each drug was extracted from FDA labels. Supportive-care treatments were excluded. Exposures:Name of drug approved, date of approval, indication, tumor type, mechanism of action, broad pharmaceutical class, and biological target. Approvals considering all tumor types and each tumor type separately were classified in 3 nonoverlapping categories: new mechanism of action, next in class, or subsequent approval. Main Outcomes and Measures:The number of all approvals each year; the number of approvals based on a new mechanism of action, either by drug (considering all tumor types) or by indication (considering tumor types separately); and the frequency of these numbers over time. Results:Overall, 332 approvals were included. Between 2009 and 2020, there was an increase in the total number of approvals from 8 to 57. We found that 209 approvals (63%) were for a next-in-class indication in a new tumor type (84 [25%]) or a subsequent indication of the same drug in the same tumor type (195 [59%]). When considering each tumor type separately, 123 approvals (37%) were based on a new mechanism of action. Conclusions and Relevance:In this study, approvals based on a new mechanism of action represented a minority of all approvals. Further consideration of incentives for drug development are needed to prioritize novel or highly innovative and transformative anticancer drugs. 10.1001/jamanetworkopen.2021.38793