Targeting the Phosphatidylinositol-3-kinase Pathway in Gastric Cancer: Can Omics Improve Outcomes?
Targeting the Phosphatidylinositol-3-kinase Pathway in Gastric Cancer: Can Omics Improve Outcomes?
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DOI：
10.5213/inj.1632740.370
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发表时间：
2016-11
影响因子：
2.3
通讯作者：
Klempner SJ
中科院分区：
文献类型：
--
作者：
Tran P;Nguyen C;Klempner SJ
磷脂酰肌醇-3-激酶(PI3K)信号转导通路是一条成熟的致癌信号转导通路，与多种恶性肿瘤密切相关。靶向PI3K途径成分的治疗改善了慢性淋巴细胞白血病、肾癌、乳腺癌和神经内分泌肿瘤的疗效。胃癌在PI3K中具有最高的致癌变异率，但将这种基因组观察转化为临床成功的尝试有限，需要新的方法。在接下来的综述中，我们讨论了PI3K信号转导，先前在胃癌中的临床前和临床研究，并讨论了未来旨在克服耐药和提高疗效的策略。分子肿瘤亚型的识别和提炼、预测生物标记物的开发和合理的药物组合策略是发挥PI3K通路导向治疗胃癌治疗潜力的关键。
Phosphatidylinositol-3-kinase (PI3K) pathway signaling is an established oncogenic signal transduction pathway implicated in multiple malignancies. Therapeutic targeting of PI3K pathway components has improved outcomes in chronic lymphocytic leukemia, kidney cancer, breast cancer, and neuroendocrine tumors. Gastric cancers harbor some of the highest rates of oncogenic alterations in PI3K but attempts to translate this genomic observation have met with limited clinical success and novel approaches are needed. In the following review we discuss PI3K signaling, previous preclinical and clinical investigations in gastric cancer, and discuss future strategies aimed at overcoming resistance and improving efficacy. Identification and refinement of molecular tumor subtypes, development of predictive biomarkers along, and rational drug combination strategies are key to capitalizing on the therapeutic potential of PI3K pathway directed therapies in gastric cancers.