Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States.
Biochem Pharmacol. 2020 Jun;176:113913. doi: 10.1016/j.bcp.2020.113913. Epub 2020 Mar 12.
Cancer is not a single disease but it constitutes a large variety of different types that are also different from each other phenotypically and molecularly. Although the standard treatments have resulted in clinical responses in a subset of patients, though, many patients relapse and no longer respond to further treatments. Hence, both the innate and adaptive resistance to treatments are the main challenges in today's treatment strategies. Noteworthy, several novel treatment strategies, particularly immunotherapies, used alone or in combination, have been developed and that have significantly improved the therapeutic response of many unresponsive cancer patients. Nevertheless, even with the latest new developments of therapeutics that were effective in a larger subset of patients, there is still an urgent need to treat the remaining unresponsive subset of patients. This requires the development of new targeting agents of superior antitumor activities that will lead to overcoming the unaffected resistance by current treatments. There has been accumulating evidence suggesting nitric oxide donors as such targeting agents and considering their pleiotropic antitumor activities, including both the reversal of chemo and immuno-resistance of various unresponsive resistant cancers. The in vitro and in vivo preclinical findings corroborate the sensitizing antitumor activities of nitric oxide donors. In addition, a few clinical findings with NO donors that have been applied in patients have corroborated their antitumor and sensitizing activities in combination with standard therapies. In this review, the role and underlying mechanisms by which nitric oxide donors sensitize cancer resistant cells to both chemotherapy and immunotherapy are briefly described.
癌症不是一种单一的疾病，而是由多种不同类型的癌症组成，这些癌症在表型和分子水平上彼此不同。尽管标准治疗方法已经使一部分患者获得了临床反应，但许多患者会复发，并且对进一步的治疗不再有反应。因此，无论是先天的还是适应性的治疗耐药性都是当今治疗策略的主要挑战。值得注意的是，已经开发了几种新的治疗策略，特别是免疫疗法，单独或联合使用，这些治疗策略显著改善了许多无反应性癌症患者的治疗反应。然而，即使是最新的治疗方法在更大的患者亚组中有效，仍然迫切需要治疗剩余的无反应性患者亚组。这需要开发具有更高抗肿瘤活性的新靶向药物，以克服当前治疗方法的未受影响的耐药性。越来越多的证据表明，一氧化氮供体可以作为这种靶向药物，并且考虑到它们具有多种抗肿瘤活性，包括逆转各种无反应性耐药性癌症的化疗和免疫耐药性。体外和体内临床前研究结果证实了一氧化氮供体的增敏抗肿瘤活性。此外，一些已经在患者中应用的 NO 供体的临床发现证实了它们与标准疗法联合应用的抗肿瘤和增敏活性。在这篇综述中，简要描述了一氧化氮供体如何使耐药性癌细胞对化疗和免疫治疗敏感的作用和潜在机制。
