School of Chinese Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
Evid Based Complement Alternat Med. 2014;2014:232946. doi: 10.1155/2014/232946. Epub 2014 Mar 13.
Molecular targeted therapy has been developed for cancer chemoprevention and treatment. Cancer cells process a fundamental change in its bioenergetic metabolism from normal cells on an altered lipid metabolism, also known as the de novo fatty acid synthesis, for sustaining their high proliferation rates. Fatty acid synthesis is now associated with clinically aggressive tumor behavior and tumor cell growth and has become a novel target pathway for chemotherapy development. Although the underlying mechanisms of the altered de novo fatty acid synthesis still remains unclear, recent progress has shown that by targeting Fatty acid synthase (FASN), a key enzyme that catalyzes the synthesis of endogenous long chain fatty acid could be a critical target for drug discovery. However, relatively few FASN inhibitors have been discovered. With the long history of clinical practices and numerous histological case study reports, traditional Chinese medicine enjoys an important role in seeking bioactive anticancer natural compounds. Herein, we will give an overall picture of the current progress of molecular targeted therapy in cancer fatty acid synthesis, describe the advances in the research on natural products-derived FASN inhibitors and their potential for enhancing our understanding of fatty acids in tumor biology, and may provide new therapeutic moieties for breast cancer patient care.
分子靶向治疗已经被开发用于癌症的化学预防和治疗。癌细胞在其生物能量代谢上发生了根本性的变化，与正常细胞不同的是，癌细胞改变了脂质代谢，即从头合成脂肪酸，以维持其高增殖率。脂肪酸合成现在与临床侵袭性肿瘤行为以及肿瘤细胞生长有关，已经成为化疗发展的新靶点途径。尽管改变的从头脂肪酸合成的潜在机制仍不清楚，但最近的进展表明，通过靶向脂肪酸合酶（FASN），一种催化内源性长链脂肪酸合成的关键酶，可以成为药物发现的关键靶点。然而，相对较少的 FASN 抑制剂已经被发现。由于长期的临床实践和大量的组织学案例研究报告，中药在寻找生物活性抗癌天然化合物方面发挥着重要作用。在此，我们将全面介绍癌症脂肪酸合成中分子靶向治疗的最新进展，描述天然产物衍生的 FASN 抑制剂的研究进展及其在增强我们对肿瘤生物学中脂肪酸的理解方面的潜力，并可能为乳腺癌患者的治疗提供新的治疗药物。
