Improving Response Rates to EGFR-Targeted Therapies for Head and Neck Squamous Cell Carcinoma: Candidate Predictive Biomarkers and Combination Treatment with Src Inhibitors.
Improving Response Rates to EGFR-Targeted Therapies for Head and Neck Squamous Cell Carcinoma: Candidate Predictive Biomarkers and Combination Treatment with Src Inhibitors.
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DOI：
10.1155/2009/896407
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发表时间：
2009
影响因子：
--
通讯作者：
Grandis JR
中科院分区：
文献类型：
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作者：
Egloff AM;Grandis JR
表皮生长因子受体 (EGFR) 导向抗体西妥昔单抗于 2006 年获得 FDA 批准用于治疗头颈鳞状细胞癌 (SCCHN)。 SCCHN 临床开发中的其他 EGFR 靶向药物包括其他 EGFR 导向抗体、酪氨酸激酶抑制剂和反义 DNA。尽管大多数 SCCHN 过度表达 EGFR，但 SCCHN 对 EGFR 靶向药物的临床反应并不明显。 SCCHN 对 EGFR 靶向治疗反应的分子预测因子尚未确定。然而，肺癌和结肠癌的分子相关研究可能会提供一些见解，这些研究的 EGFR 靶向疗法已获得 FDA 批准用于治疗。我们描述了 SCCHN 对 EGFR 靶向治疗反应的候选预测标志物及其在 SCCHN 中的患病率。靶向治疗联合治疗可能会改善临床反应。 Src 家族激酶在包括 SCCHN 在内的许多癌症中介导 EGFR 依赖性和非依赖性肿瘤进展途径。几种 Src 靶向药物正处于针对实体恶性肿瘤的临床开发中。 Src 靶向治疗的分子相关研究很少，与患者反应相关的生物标志物也有限。确定对 EGFR 和 Src 联合靶向有反应的 SCCHN 患者需要进一步表征分子相关性。我们讨论了 EGFR 和 Src 共同靶向 SCCHN 治疗的基本原理，并描述了最近实施 Src 和 EGFR 联合靶向治疗的临床试验。
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.