Gougis Paul, Moreau Bachelard Camille, Kamal Maud, Gan Hui K, Borcoman Edith, Torossian Nouritza, Bièche Ivan, Le Tourneau Christophe
Department of Drug Development and Innovation (D3i), Institut Curie, Paris & Saint-Cloud, France.
AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, CLIP Galilée, Paris, France.
JNCI Cancer Spectr. 2019 Nov 12;3(4):pkz055. doi: 10.1093/jncics/pkz055. eCollection 2019 Dec.
A better understanding of cancer biology has led to the development of molecular targeted therapy, which has dramatically improved the outcome of some cancer patients, especially when a biomarker of efficacy has been used for patients' selection. In head and neck oncology, cetuximab that targets epidermal growth factor receptor is the only targeted therapy that demonstrated a survival benefit, both in the recurrent and in the locally advanced settings, yet without prior patients' selection. We herein review the clinical development of targeted therapy in head and neck squamous cell carcinoma in light of the molecular landscape and give insights in on how innovative clinical trial designs may speed up biomarker discovery and deployment of new molecular targeted therapies. Given the recent approval of immune checkpoint inhibitors targeting programmed cell death-1 in head and neck squamous cell carcinoma, it remains to be determined how targeted therapy will be incorporated into a global drug development strategy that will inevitably incorporate immunotherapy.
对癌症生物学的深入理解推动了分子靶向治疗的发展,这显著改善了一些癌症患者的治疗效果,尤其是在使用疗效生物标志物进行患者选择时。在头颈肿瘤学中,靶向表皮生长因子受体的西妥昔单抗是唯一一种在复发和局部晚期情况下均显示出生存获益的靶向治疗药物,且无需事先进行患者选择。我们在此根据分子格局综述头颈部鳞状细胞癌靶向治疗的临床进展,并就创新的临床试验设计如何加速生物标志物发现以及新分子靶向治疗的应用提供见解。鉴于最近针对程序性细胞死亡蛋白1的免疫检查点抑制剂已获批用于头颈部鳞状细胞癌,靶向治疗将如何纳入不可避免地会包含免疫治疗的全球药物开发策略仍有待确定。