Perioperative biobehavioral interventions to prevent cancer recurrence through combined inhibition of β-adrenergic and cyclooxygenase 2 signaling.
Perioperative biobehavioral interventions to prevent cancer recurrence through combined inhibition of β-adrenergic and cyclooxygenase 2 signaling.
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DOI：
10.1002/cncr.31594
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发表时间：
2019-01-01
期刊：
影响因子：
6.2
通讯作者：
Ben-Eliyahu, Shamgar
中科院分区：
文献类型：
--
作者：
Ricon, Itay;Hanalis-Miller, Tsipi;Haldar, Rita;Jacoby, Rebecca;Ben-Eliyahu, Shamgar
关键词：
有证据表明，交感神经系统（SNS）的过度围手术期激活和随之而来的儿茶酚胺（即，肾上腺素和去甲肾上腺素）可以显著促进促转移过程。这篇综述首先介绍了生物医学过程，使围手术期的时间范围在确定长期癌症的结果，不成比例的短持续时间（天-周）的关键。然后，我们分析了各种机制，通过这些机制，过量释放的儿茶酚胺可以促进癌症转移的进展，在这种情况下，通过直接影响恶性组织，并通过间接途径，调节免疫和其他机制，影响肿瘤微环境和全身转移进展。此外，我们提出需要用COX 2抑制补充β-肾上腺素受体阻滞剂，特别是在手术期间和手术后不久，因为手术诱导的炎症反应同时激活了类似的机制。重要的是，我们提供了翻译和临床证据，证明围手术期β-肾上腺素受体阻滞剂和COX 2抑制剂可以减少促转移过程和癌症复发，以及这种方法的临床可行性和安全性。最后，我们提出了使用β-肾上腺素能受体阻滞剂的心理-生理替代方法，因为相当一部分患者对这种药物治疗有医学禁忌症。适应现有的心理生理干预围手术期，以及构建新的方法的原则进行了讨论和举例说明。总体而言，单独或联合的药物行为干预可以将围手术期时间从转移进展的主要促进因素转变为阻止或消除残留疾病的机会，从而可能提高癌症患者的长期生存率。基于动物模型、回顾性临床研究和最近的随机对照试验（RCT）的证据表明，同时使用β受体阻滞剂和COX 2抑制剂可以有效降低围手术期应激-炎症反应的促恶性效应，并可能降低患者的复发率和死亡率。假设，围手术期心理干预可能有类似的好处。
Evidence suggests that excess perioperative activation of the sympathetic nervous system (SNS) and the consequent release of catecholamines (i.e., epinephrine and norepinephrine) in the context of cancer surgery and inflammation may significantly facilitate pro-metastatic processes. This review first presents biomedical processes that make the perioperative timeframe pivotal in determining long-term cancer outcomes, non-proportionally to its short duration (days-weeks). We then analyze the various mechanisms via which excess release of catecholamines can facilitate progression of cancer metastases in this context, through directly affecting the malignant tissues, and through indirect pathways, regulating immunological and other mechanisms that affect metastatic progression in the tumor microenvironment and systemically. Additionally, we address the need to supplement β-adrenoreceptor blockade with COX2 inhibition, especially during surgery and shortly thereafter, given that similar mechanisms are simultaneously activated by surgery-induced inflammatory responses. Importantly, we present translational and clinical evidence that perioperative β-adrenoreceptor blockade and COX2 inhibition can reduce pro-metastatic process and cancer recurrence, and the clinical feasibility and safety of this approach. Last, we present psycho-physiological alternative approaches to the use of β-adrenergic blockers, as a substantial portion of patients have medical contraindications to this pharmacological treatment. Adaptation of existing psycho-physiological interventions to the perioperative period, as well as principles of constructing new approaches are discussed and exemplified. Overall, pharmaco-behavioral interventions, separately or combined, could transform the perioperative timeframe from being a prominent facilitator of metastatic progression, to an opportunity for arresting or eliminating residual disease, potentially improving long-term survival rates in cancer patients. Evidence based on animal models, retrospective clinical studies, and recently also randomized controlled trials (RCTs), indicate that simultaneous use of beta-blockers and COX2 inhibitors can effectively reduce pro-malignant effects of perioperative stress-inflammatory responses, and may reduce patients recurrence rates and mortality. Hypothetically, perioperative psychological interventions may have similar benefits.
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