Aviles Diego, Warshal David, Buchbinder Michelle, Ostrovsky Olga
Department of Gynecologic Oncology, MD Anderson Cancer Center at Cooper, Cooper University Health Case, Camden, NJ, USA
Cooper Medical School of Rowan University, Camden, NJ, USA
Metastasis in ovarian cancer is a primary driver of poor outcomes for patients because of its association with chemoresistance and low five-year survival rates. Epigenetic changes to gene expression in cancer cells are key factors that contribute to the high rates of metastasis and chemoresistance. However, ovarian cancer cells do not act alone. Once the cancer spreads to the omentum and peritoneum, it hijacks intercellular communication systems to transform neighboring cells within the tumor microenvironment into potent engines that produce critical growth factors that facilitate metastasis, chemoresistance, immune evasion, and invasion. By reversing these aberrant epigenetic modifications in cancer cells and the tumor microenvironment, novel epigenetic therapies can specifically target cancer cells while sparing healthy cells, minimizing toxicity to normal tissues. When combining these pharmaceutical agents with standard chemotherapy, metastasis and chemoresistance can be suppressed, making ovarian cancer cells newly susceptible to current cytotoxic treatments, and providing patients with hope for a cure.
卵巢癌转移是患者预后不良的主要驱动因素，因为它与化疗耐药性以及低五年生存率相关。癌细胞中基因表达的表观遗传变化是导致高转移率和化疗耐药性的关键因素。然而，卵巢癌细胞并非单独起作用。一旦癌症扩散到网膜和腹膜，它就会劫持细胞间通讯系统，将肿瘤微环境中的邻近细胞转化为强大的引擎，产生促进转移、化疗耐药性、免疫逃逸和侵袭的关键生长因子。通过逆转癌细胞和肿瘤微环境中这些异常的表观遗传修饰，新型表观遗传疗法可以特异性地靶向癌细胞，同时 sparing healthy cells，将对正常组织的毒性降至最低。当将这些药物与标准化疗相结合时，可以抑制转移和化疗耐药性，使卵巢癌细胞对当前的细胞毒性治疗重新敏感，并为患者提供治愈的希望。 （注：原文中“sparing healthy cells”表述有误，推测可能是“sparing healthy tissues”，即“ sparing healthy tissues，将对正常组织的毒性降至最低” ）
