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癌症治疗中的三剑客:药代动力学、药效学和个体化方法

英文原题:The Three Musketeers in Cancer Therapy: Pharmacokinetics, Pharmacodynamics and Personalised Approach.

PubMed 2025/10/31(内容时间) J Pers Med

研究概要

癌症治疗正迅速从一刀切的模式向高度个性化的方法演变。

中文摘要

癌症治疗正迅速从一刀切的模式向高度个性化的方法演变。传统化疗和放疗虽然应用广泛,但由于肿瘤异质性,往往疗效欠佳,且受到显著毒性的限制。相比之下,精准肿瘤学根据个体患者的遗传和分子特征来定制预防、诊断和治疗方案。关键进展凸显了这一转变:分子靶向药物(如用于HER2阳性乳腺癌的曲妥珠单抗、用于肺癌的EGFR和ALK抑制剂)与传统治疗相比,提高了疗效并降低了毒性。药代动力学(PK)和药效动力学(PD)考量是个性化治疗的核心,可解释患者间药物暴露和反应的差异,并指导剂量优化。治疗药物监测和模型引导的精准给药等现代策略旨在将药物浓度维持在治疗范围内,从而改善预后。免疫疗法,包括检查点抑制剂和CAR-T细胞,已经改变了肿瘤学格局,但通过生物标志物(如PD-L1表达或肿瘤突变负荷)进行患者筛选对于识别可能应答者至关重要。创新药物递送系统,尤其是纳米医学,通过增强肿瘤特异性药物蓄积和实现新型治疗手段来应对PK挑战。此外,基于PK/PD和肿瘤生物学的合理联合方案正在被设计,以实现协同疗效并克服耐药性。主要障碍包括生物标志物检测的高成本、实验室基础设施不足以及报销政策不一致。诸如周转时间长或临床医生认知不足等运营效率低下的问题,进一步限制了精准诊断的使用。监管流程也仍然复杂,尤其是在靶向药物与伴随诊断的共同开发以及罕见亚组的证据要求方面。解决这些障碍需要协调一致的政策、对基础设施的投资以及教育举措,以确保个性化医疗的前景能够惠及所有患者。确保相关进展以负责任的方式落地——以药理学洞见为指导,以真实世界证据为支持,并在伦理和经济框架内加以评估——对于充分实现个性化肿瘤医学的潜力至关重要。

展开英文摘要原文

Cancer therapy is rapidly evolving from a one-size-fits-all paradigm toward highly personalized approaches. Traditional chemotherapies and radiotherapies, while broadly applied, often yield suboptimal outcomes due to tumor heterogeneity and are limited by significant toxicities. In contrast, precision oncology tailors prevention, diagnosis, and treatment to the individual patient's genetic and molecular profile. Key advancements underscore this shift: molecularly targeted drugs (e.g., trastuzumab for HER2-positive breast cancer, EGFR and ALK inhibitors for lung cancer) have improved efficacy and reduced toxicity compared to conventional therapy. Pharmacokinetic (PK) and pharmacodynamic (PD) considerations are central to personalizing treatment, explaining variability in drug exposure and response among patients and guiding dose optimization. Modern strategies like therapeutic drug monitoring and model-informed precision dosing seek to maintain drug levels in the therapeutic range, improving outcomes. Immunotherapies, including checkpoint inhibitors and CAR-T cells, have transformed oncology, though patient selection via biomarkers (such as PD-L1 expression or tumor mutational burden) is critical to identify likely responders. Innovative drug delivery systems, notably nanomedicine, address PK challenges by enhancing tumor-specific drug accumulation and enabling novel therapeutics. Furthermore, rational combination regimens (informed by PK/PD and tumor biology) are being designed to achieve synergistic efficacy and overcome resistance. Key barriers include the high cost of biomarker testing, insufficient laboratory infrastructure, and inconsistent reimbursement policies. Operational inefficiencies such as long turnaround times or lack of clinician awareness further limit the use of precision diagnostics. Regulatory processes also remain complex, particularly around the co-development of targeted drugs and companion diagnostics, and the evidentiary requirements for rare subgroups. Addressing these barriers will require harmonized policies, investment in infrastructure, and educational initiatives to ensure that the promise of personalized medicine becomes accessible to all patients. Ensuring that advances are implemented responsibly-guided by pharmacological insights, supported by real-world evidence, and evaluated within ethical and economic frameworks-will be critical to realizing the full potential of personalized cancer medicine.

论文信息

作者
Zarić M、Čanović P、Živković Zarić R、Protrka S、Glišić M
第一作者单位
Department of Biochemistry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, Serbia.
通讯作者单位
Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, Serbia.
文献类型
综述
期刊
Journal of personalized medicine2025 Oct 31
原文标识
PubMed 41295218 · DOI 10.3390/jpm15110516