Jones Helen E, Gee Julia Mw, Hutcheson Iain R, Nicholson Robert I
a Cardiff University, Tenovus Centre for Cancer Research, King Edward VII Avenue, Cardiff CF10 3XF, UK.
Expert Rev Endocrinol Metab. 2006 Jan;1(1):33-46. doi: 10.1586/17446651.1.1.33.
Insulin-like growth factor-I receptor (IGF-IR) signaling is involved in many fundamental adverse aspects of cancer cell biology, such as proliferation, cell survival and migration. Its anti-apoptotic properties have implicated the receptor in mediating decreased sensitivity to chemotherapeutic drugs and radiation treatment; however, data are emerging that also indicates a role for IGF-IR signaling in resistance, not only to antihormones but also to antigrowth factor strategies such as agents that target the erb family of receptors. As such, IGF-IR is clearly an attractive therapeutic target for the treatment of cancer, including breast cancer, where there is evidence of clinical prominence of the IGF-IR pathway and, as such, numerous strategies are currently in development to inhibit IGF-IR signaling. This review focuses on the ability of the IGF-IR to contribute to resistance mechanisms that support breast cancer cell growth in the presence of antihormones and antigrowth factors and discusses methods to maximize antitumor effects by combination regimens cotargeting the IGF-IR that may delay, or even prevent, progression to the resistant phenotype.
胰岛素样生长因子-I受体（IGF-IR）信号传导参与癌细胞生物学的许多基本不良方面，如增殖、细胞存活和迁移。其抗凋亡特性表明该受体介导了对化疗药物和放射治疗敏感性的降低；然而，新出现的数据也表明IGF-IR信号传导不仅在对抗激素耐药中起作用，而且在对抗生长因子策略（如靶向erb受体家族的药物）耐药中也起作用。因此，IGF-IR显然是治疗癌症（包括乳腺癌）的一个有吸引力的治疗靶点，在乳腺癌中，有证据表明IGF-IR途径在临床上很突出，因此目前正在开发多种抑制IGF-IR信号传导的策略。本综述重点关注IGF-IR在抗激素和抗生长因子存在的情况下促进支持乳腺癌细胞生长的耐药机制的能力，并讨论通过联合靶向IGF-IR的方案来最大化抗肿瘤效果的方法，这些方案可能延迟甚至防止进展为耐药表型。
