Washington University in St. Louis, Medicine, 660 S. Euclid Ave, Box 8056, St. Louis, MO 63110, USA.
Expert Opin Investig Drugs. 2013 Mar;22(3):341-56. doi: 10.1517/13543784.2013.761972. Epub 2013 Jan 15.
Gastrointestinal (GI) malignancies account for nearly one-fourth of all cancer-related deaths in the United States and approximately 30% of all cancer-related deaths worldwide. Use of combination cytotoxic therapy offers a modest improvement in survival, but the prognosis and long-term survival of most patients with GI cancer remains poor. In certain GI malignancies, therapies that target members of the HER family of receptors have positively impacted patient care.
In this review, we discuss the significance of the HER family of receptors in esophagogastric, hepatobiliary, pancreatic, and colorectal cancers and explain the rationale supporting the use of monoclonal antibodies (mAbs) and small molecule tyrosine kinase inhibitors (TKIs) to inhibit HER activation and downstream events that contribute to tumor proliferation, migration, and survival.
Despite recent advances, the treatment of GI cancers remains challenging. Therapies targeting the HER family of receptors have been extensively studied in these malignancies with inconsistent results. The rationale behind varied tumor responses with these agents remains uncertain. We believe that additional studies are needed to identify biomarkers that could help identify a population of patients who would be more responsive to a given therapy.
在美国，胃肠道（GI）恶性肿瘤约占所有癌症相关死亡人数的四分之一，约占全球所有癌症相关死亡人数的 30%。联合细胞毒性疗法的使用略微改善了生存，但大多数胃肠道癌症患者的预后和长期生存仍然较差。在某些胃肠道恶性肿瘤中，针对 HER 受体家族成员的治疗方法已对患者护理产生了积极影响。
在这篇综述中，我们讨论了 HER 受体家族在食管胃、肝胆胰腺和结直肠癌症中的意义，并解释了支持使用单克隆抗体（mAbs）和小分子酪氨酸激酶抑制剂（TKIs）抑制 HER 激活以及有助于肿瘤增殖、迁移和存活的下游事件的基本原理。
尽管最近取得了进展，但胃肠道癌症的治疗仍然具有挑战性。针对这些恶性肿瘤的 HER 受体家族的治疗方法已经进行了广泛研究，但结果不一致。这些药物引起不同肿瘤反应的基本原理尚不确定。我们认为需要进一步研究以确定生物标志物，以帮助确定对特定治疗更敏感的患者群体。
