Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
J Oncol. 2009;2009:896407. doi: 10.1155/2009/896407. Epub 2009 Jul 14.
The epidermal growth factor receptor- (EGFR-) directed antibody, cetuximab, was FDA-approved for the treatment of squamous cell carcinoma of the head and neck (SCCHN) in 2006. Additional EGFR-targeting agents in clinical development for SCCHN include other EGFR-directed antibodies, tyrosine kinase inhibitors and antisense DNA. Although the majority of SCCHN overexpress EGFR, SCCHN clinical responses to EGFR-targeting agents have been modest. Molecular predictors for SCCHN response to EGFR-targeted therapies have not been identified. However, molecular correlate studies in lung cancer and colon cancer, which have EGFR-targeted therapeutics FDA-approved for treatment, may provide insights. We describe candidate predictive markers for SCCHN response to EGFR-targeted therapies and their prevalence in SCCHN. Clinical response will likely be improved by targeted therapy combination treatments. Src family kinases mediate EGFR-dependent and -independent tumor progression pathways in many cancers including SCCHN. Several Src-targeting agents are in clinical development for solid malignancies. Molecular correlate studies for Src-targeting therapies are few and biomarkers correlated with patient response are limited. Identifying SCCHN patients who will respond to combined EGFR- and Src-targeting will require further characterization of molecular correlates. We discuss rationale for EGFR and Src co-targeting for SCCHN treatment and describe recent clinical trials implementing combined Src- and EGFR-targeted therapeutics.
表皮生长因子受体-（EGFR-）定向抗体西妥昔单抗于 2006 年获得美国食品和药物管理局（FDA）批准用于治疗头颈部鳞状细胞癌（SCCHN）。其他正在开发用于治疗 SCCHN 的 EGFR 靶向药物包括其他 EGFR 定向抗体、酪氨酸激酶抑制剂和反义 DNA。尽管大多数 SCCHN 过表达 EGFR，但 SCCHN 对 EGFR 靶向药物的临床反应较为温和。尚未确定 SCCHN 对 EGFR 靶向治疗的分子预测因子。然而，在肺癌和结肠癌中的分子相关性研究可能提供了一些见解，这两种癌症都有 EGFR 靶向治疗药物获得 FDA 批准用于治疗。我们描述了用于预测 SCCHN 对 EGFR 靶向治疗反应的候选标志物及其在 SCCHN 中的发生率。通过靶向治疗联合治疗可能会改善临床反应。在许多癌症中，包括 SCCHN，Src 家族激酶介导 EGFR 依赖性和非依赖性肿瘤进展途径。几种 Src 靶向药物正在开发用于实体恶性肿瘤。用于 Src 靶向治疗的分子相关性研究很少，与患者反应相关的生物标志物也有限。确定将对 EGFR 和 Src 联合靶向治疗有反应的 SCCHN 患者需要进一步确定分子相关性。我们讨论了针对 SCCHN 治疗进行 EGFR 和 Src 联合靶向治疗的原理，并描述了最近实施联合 Src 和 EGFR 靶向治疗的临床试验。
