Medical and Experimental Oncology Unit, Cancer Institute Giovanni Paolo II, Bari, Italy.
Oncology. 2009;77 Suppl 1:69-74. doi: 10.1159/000258498. Epub 2010 Feb 2.
Wild-type KRAS status is required but not sufficient to confer sensitivity to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) in colorectal cancer patients. As a consequence, one of the major challenges is to identify, in non-mutant KRAS patients, other markers that can predict lack of response to this therapy. Small series have investigated the clinical effect of PIK3CA mutations on resistance to anti-EGFR mAbs and discrepant results have been observed. Furthermore, PTEN loss in metastases may be predictive of resistance to anti-EGFR mAbs, even if PTEN determination is far from an immediate clinical application. The introduction of modulators of the PI3K/AKT/mTOR pathway as potential targeted anticancer drugs is encouraging, but this attractive therapy option is still at an early stage of development.
野生型 KRAS 状态是结直肠癌患者对表皮生长因子受体（EGFR）单克隆抗体（mAb）敏感所必需的，但不是充分条件。因此，主要挑战之一是在非突变型 KRAS 患者中确定其他可预测对该治疗无反应的标志物。一些小系列研究了 PIK3CA 突变对抗 EGFR mAb 耐药性的临床影响，但观察到的结果不一致。此外，转移灶中 PTEN 的缺失可能预示着对抗 EGFR mAb 的耐药性，即使 PTEN 测定远非一种即时的临床应用。PI3K/AKT/mTOR 通路调节剂作为潜在的靶向抗癌药物的引入令人鼓舞，但这种有吸引力的治疗选择仍处于早期开发阶段。
