Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, Australia; Department of Medical Oncology, Olivia Newton-John Cancer and Wellness Centre, Austin Health, Heidelberg, Melbourne, Australia; School of Cancer Medicine, La Trobe University, Melbourne, Australia.
Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, Australia; School of Cancer Medicine, La Trobe University, Melbourne, Australia.
Cancer Treat Rev. 2017 Sep;59:1-21. doi: 10.1016/j.ctrv.2017.06.005. Epub 2017 Jul 6.
The development of HER2-directed monoclonal antibodies and tyrosine kinase inhibitors have provided benefits to cancer patients, as well as produced many insights into the biology of the ErbB receptor family. Current therapies based on ErbB family members have resulted in improved overall survival with associated improvements in quality of life for the cancer patients that respond to treatment. Compared to monotherapy using either two antibodies to block the HER2 receptor blockade or combinatorial approaches with HER2 antibodies and standard therapies has provided additional benefits. Despite the therapeutic success of existing HER2 therapies, personalising treatment and overcoming resistance to these therapies remains a significant challenge. The heterogeneous intra-tumoural HER2 expression and lack of fully predictive and prognostic biomarkers remain significant barriers to improving the use of HER2 antibodies. Imaging modalities using radiolabelled pertuzumab and trastuzumab allow quantitative assessment of intra-tumoural HER2 expression, HER2 antibody saturation and the success of different drug delivery systems to be assessed. Molecular imaging with HER2 antibodies has the potential to be a non-invasive, predictive and prognostic technique capable of influencing therapeutic decisions, predicting response and failure of treatments as well as providing insights into receptor recycling and signalling. Similarly, conjugating HER2 antibodies with novel toxic payloads or combining HER2 antibodies with cellular immunotherapy provide exciting new opportunities for the management of tumours overexpressing HER2. Future research will lead to higher therapeutic responses, lower toxicities and providing insight into the mechanisms of resistance to HER2-targeted treatments.
曲妥珠单抗和酪氨酸激酶抑制剂的发展为癌症患者带来了益处，同时也深入了解了 ErbB 受体家族的生物学特性。基于 ErbB 家族成员的当前疗法已经改善了总体生存率，并提高了对治疗有反应的癌症患者的生活质量。与使用两种抗体阻断 HER2 受体或使用 HER2 抗体和标准疗法联合治疗的单一疗法相比，这些疗法具有额外的益处。尽管现有的 HER2 治疗取得了治疗成功，但针对这些疗法的个性化治疗和克服耐药性仍然是一个重大挑战。肿瘤内 HER2 表达的异质性以及缺乏完全预测性和预后性生物标志物仍然是提高 HER2 抗体使用的重大障碍。使用放射性标记的曲妥珠单抗和 pertuzumab 的成像方式可以定量评估肿瘤内 HER2 表达、HER2 抗体饱和以及不同药物输送系统的成功。HER2 抗体的分子成像有可能成为一种非侵入性、预测性和预后性技术，能够影响治疗决策、预测治疗反应和失败，以及深入了解受体循环和信号转导。同样，将 HER2 抗体与新型毒性有效载荷结合，或将 HER2 抗体与细胞免疫疗法结合，为过度表达 HER2 的肿瘤的管理提供了令人兴奋的新机会。未来的研究将带来更高的治疗反应、更低的毒性，并深入了解针对 HER2 靶向治疗的耐药机制。
