Parkville Integrated Palliative Care Service, The Royal Melbourne Hospital, 300 Grattan St, Parkville, Victoria, 3050, Australia.
Department of Medicine, University of Melbourne, Eastern Hill Campus, Victoria Parade, Fitzroy, Victoria, 3065, Australia.
Curr Treat Options Oncol. 2022 Oct;23(10):1353-1369. doi: 10.1007/s11864-022-01010-x. Epub 2022 Aug 24.
Pharmacogenomics is increasingly important to guide objective, safe, and effective individualised prescribing. Personalised prescribing has revolutionised treatments in the past decade, allowing clinicians to maximise drug efficacy and minimise adverse effects based on a person's genetic profile. Opioids, the gold standard for cancer pain relief, are among the commonest medications prescribed in palliative care practice. This narrative review examines the literature surrounding opioid pharmacogenomics and its applicability to the palliative care cancer population. There is currently limited intersection between the fields of palliative care and pharmacogenomics, but growing evidence presents a need to build linkages between the two disciplines. Pharmacogenomic evidence guiding opioid prescribing is currently available for codeine and tramadol, which relates to CYP2D6 gene variants. However, these medications are prescribed less commonly for pain in palliative care. Research is accelerating with other opioids, where oxycodone (CYP2D6) and methadone (CYP2B6, ABCB1) already have moderate evidence of an association in terms of drug metabolism and downstream analgesic response and side effects. OPRM1 and COMT are receiving increasing attention and have implications for all opioids, with changes in opioid dosage requirements observed but they have not yet been studied widely enough to be considered clinically actionable. Current evidence indicates that incorporation of pharmacogenomic testing into opioid prescribing practice should focus on the CYP2D6 gene and its actionable variants. Although opioid pharmacogenomic tests are not widely used in clinical practice, the progressively reducing costs and rapid turnover means greater accessibility and affordability to patients, and thus, clinicians will be increasingly asked to provide guidance in this area. The upsurge in pharmacogenomic research will likely discover more actionable gene variants to expand international guidelines to impact opioid prescribing. This rapidly expanding area requires consideration and monitoring by clinicians in order for key findings with clinical implications to be accessible, meaningfully interpretable and communicated.
药物基因组学对于指导客观、安全和有效的个体化处方越来越重要。个体化处方在过去十年中彻底改变了治疗方法,使临床医生能够根据患者的基因谱最大限度地提高药物疗效并减少不良反应。阿片类药物是缓解癌症疼痛的金标准,也是姑息治疗实践中最常开的药物之一。这篇叙述性综述探讨了阿片类药物基因组学及其在姑息治疗癌症人群中的应用的相关文献。姑息治疗和药物基因组学这两个领域目前交集有限,但越来越多的证据表明需要在这两个学科之间建立联系。目前,指导阿片类药物处方的药物基因组学证据可用于可待因和曲马多,这与 CYP2D6 基因变异有关。然而,这些药物在姑息治疗中较少用于疼痛治疗。随着其他阿片类药物的研究加速,羟考酮(CYP2D6)和美沙酮(CYP2B6、ABCB1)在药物代谢和下游镇痛反应和副作用方面已经有了中等程度的关联证据。OPRM1 和 COMT 越来越受到关注,并且对所有阿片类药物都有影响,观察到阿片类药物剂量需求的变化,但尚未进行广泛研究,因此还不能认为具有临床可操作性。目前的证据表明,将药物基因组学检测纳入阿片类药物处方实践应集中在 CYP2D6 基因及其可操作的变异上。尽管阿片类药物基因组学检测在临床实践中尚未广泛应用,但成本的逐渐降低和快速更新意味着患者更容易获得和负担得起,因此,临床医生将越来越多地被要求在这一领域提供指导。药物基因组学研究的兴起可能会发现更多可操作的基因变异,以扩大国际指南,影响阿片类药物的处方。这一迅速发展的领域需要临床医生的关注和监测,以便能够获得具有临床意义的关键发现,并进行有意义的解释和交流。