Diabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles , Los Angeles, CA , USA ; Keck School of Medicine, University of Southern California , Los Angeles, CA , USA.
Diabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles , Los Angeles, CA , USA ; Department of Pediatrics, Keck School of Medicine, University of Southern California , Los Angeles, CA , USA ; Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California , Los Angeles, CA , USA.
Front Pediatr. 2014 Jun 5;2:53. doi: 10.3389/fped.2014.00053. eCollection 2014.
Obesity is responsible for ~90,000 cancer deaths/year, increasing cancer incidence and impairing its treatment. Obesity has also been shown to impact hematological malignancies, through as yet unknown mechanisms. Adipocytes are present in bone marrow and the microenvironments of many types of cancer, and have been found to promote cancer cell survival. In this review, we explore several ways in which obesity might cause leukemia treatment resistance. Obese patients may be at a treatment disadvantage due to altered pharmacokinetics of chemotherapy and dosage "capping" based on ideal body weight. The adipose tissue provides fuel to cancer cells in the form of amino acids and free fatty acids. Adipocytes have been shown to cause cancer cells to resist chemotherapy-induced apoptosis. In addition, obese adipose tissue is phenotypically altered, producing a milieu of pro-inflammatory adipokines and cytokines, some of which have been linked to cancer progression. Given the prevalence of obesity, understanding its role and adipose tissue in acute lymphoblastic leukemia treatment is necessary for evaluating current treatment regimen and revealing new therapeutic targets.
肥胖症导致每年约有 9 万人因癌症死亡，增加了癌症发病率并影响了癌症的治疗效果。肥胖症也被证明会通过尚未明确的机制影响血液系统恶性肿瘤。脂肪细胞存在于骨髓和许多类型癌症的微环境中，并且已被发现可促进癌细胞的存活。在这篇综述中，我们探讨了肥胖症可能导致白血病治疗耐药的几种方式。由于改变了化疗的药代动力学和基于理想体重的剂量“封顶”，肥胖患者可能在治疗中处于不利地位。脂肪组织以氨基酸和游离脂肪酸的形式为癌细胞提供燃料。已经表明脂肪细胞会导致癌细胞抵抗化疗诱导的细胞凋亡。此外，肥胖的脂肪组织表型发生改变，产生促炎脂肪因子和细胞因子的环境，其中一些与癌症进展有关。鉴于肥胖症的普遍性，了解其在急性淋巴细胞白血病治疗中的作用和脂肪组织对于评估当前的治疗方案和揭示新的治疗靶点是必要的。
