■免疫检查点抑制剂(CPIs)已在许多早期和晚期恶性肿瘤中广泛采用。已经提出组蛋白脱乙酰酶抑制剂(HDACis)和烷化剂(AAs)增强CPIs对肿瘤细胞的作用。我们进行了全面的文献综述,以探索CPIs之间的潜在协同活性。AAS,和HDACis。
■在PubMed中使用预定义的搜索字符串识别了临床和非临床研究,这些研究描述了接受CPIs和伴随或序贯(CPI前或后)AA或HDACis的癌症患者的预后。类似地进行关键肿瘤学大会的手动搜索。所有相关文章和摘要都是手动筛选相关性的,根据使用的特定抗癌剂(CPIs,AAS,或HDACis),肿瘤实体,以及治疗是否伴随或序贯。
■总的来说,针对一系列肿瘤类型的227项独特临床研究,实体瘤和血液恶性肿瘤,已确定。审查了关于I期和II期临床研究的109种出版物以及关于III期研究的41种出版物。最常见的肿瘤类型是黑色素瘤,三阴性乳腺癌,非小细胞肺癌,和霍奇金淋巴瘤.随机临床研究确定,所有这些都报告了CPI与AA的组合,与CPI或AA单药治疗相比,联合治疗组的结局更好。同样,CPIs和HDACis的联合治疗证明了有希望的活性。
■CPI与AA或HDACi的序贯或伴随给药可以改善患有多种肿瘤类型的患者的预后。有理由支持对CPI之间协同作用的潜力进行进一步调查,烷化剂和/或HDAC在非临床和临床设置。
接受癌症治疗的人通常一次会接受一种以上的药物,和癌症药物联合治疗的概念经常被认为是改善患者预后的潜在机会。我们回顾了已发表的临床试验文献和实验室开展的工作,以探索将阻止癌细胞增殖的靶向药物(称为检查点抑制剂)与杀死癌细胞的传统化学疗法相结合是否可能是一种有用的方法。我们在出版物中看到了在化疗的同时使用检查点抑制剂的证据,或在化疗前或后立即给予。最重要的证据来自临床试验,其中直接将接受联合治疗的患者的结果与接受单一治疗的患者的结果进行比较。这些研究表明,与接受单一疗法的患者相比,接受癌症药物组合治疗的患者的预后更好。我们还发现了添加另一类抗癌药物的证据,称为组蛋白脱乙酰酶抑制剂,可能会使肿瘤对检查点抑制剂敏感。这些发现为检查烷化剂和/或组蛋白脱乙酰酶抑制剂与检查点抑制剂的组合提供了理论基础。
UNASSIGNED: Immune checkpoint inhibitors (CPIs) have been widely adopted in a number of early and advanced malignancies. Histone deacetylase inhibitors (HDACis) and alkylating agents (AAs) have been suggested to potentiate the actions of CPIs on tumor cells. We conducted a comprehensive literature review to explore the potential synergistic activity between CPIs, AAs, and HDACis.
UNASSIGNED: Clinical and non-clinical studies describing outcomes in patients with cancer receiving CPIs and either concomitant or sequential (pre- or post-CPI) AAs or HDACis were identified in PubMed using pre-defined search strings. Manual searches of key oncology congresses were similarly performed. All relevant articles and abstracts were manually screened for relevance, classified according to the specific anticancer agents used (CPIs, AAs, or HDACis), tumor entity, and whether treatment was concomitant or sequential.
UNASSIGNED: Overall, 227 unique clinical studies across a range of tumor types, both solid tumors and hematological malignancies, were identified. One hundred and fifty-nine publications on Phase I and II clinical studies together with 41 publications on Phase III studies were examined. The most commonly investigated tumor types were melanoma, triple-negative breast cancer, non-small cell lung cancer, and Hodgkin lymphoma. The randomized clinical studies identified, all of which reported on the combination of a CPI with an AA, demonstrated superior outcomes in the combination arm compared with CPI or AA monotherapy. Similarly, combination therapy with CPIs and HDACis demonstrated promising activity.
UNASSIGNED: Sequential or concomitant administration of a CPI with an AA or an HDACi may improve outcomes for patients with a range of tumor types. There is a rationale to support further investigation into the potential for synergy between CPIs, alkylating agents and/or HDACis in both the non-clinical and clinical settings.
People being treated for cancer will often receive more than one drug at a time, and the concept of combining cancer drugs is frequently investigated as a potential opportunity to improve outcomes for patients. We reviewed the published literature for clinical trials and work undertaken in laboratories to explore whether combining targeted agents that stop cancer cells from multiplying (known as checkpoint inhibitors) with traditional chemotherapy that kills cancer cells could be a useful approach. We looked at evidence in publications where checkpoint inhibitors were used at the same time as chemotherapy, or given immediately before or after chemotherapy. The most important evidence came from clinical trials where outcomes for patients receiving combinations of treatment were directly compared with those from patients receiving a single treatment. These studies showed superior outcomes for patients who were treated with a combination of cancer drugs compared with patients receiving monotherapy. We also found evidence that adding another class of cancer drug, called histone deacetylase inhibitors, might sensitize tumors to checkpoint inhibitors. These findings provide a rationale for examining alkylating agents and/or histone deacetylase inhibitors combined with checkpoint inhibitors.