Le Tourneau Christophe, Faivre Sandrine, Raymond Eric
Service Inter-Hospitalier de Cancérologie, Bichat-Beaujon Beaujon University Hospital, Clichy, France.
Oncology (Williston Park). 2007 Aug;21(9 Suppl 3):21-4.
Integrins have direct effects in stimulating proliferation and preventing apoptosis in cancer cells and mediating proangiogenic interactions between endothelial cells and extracellular matrix. Alterations of expression of various integrins and their receptors have been observed in various cancers in which angiogenesis is known to play a role, including colorectal cancer. Inhibition of specific integrins might thus inhibit both direct effects of integrins on cancer cells and tumor angiogenesis. Inhibitory peptides and anti-integrin monoclonal antibodies are currently being investigated in clinical trials in patients with solid tumors, with early evidence suggesting clinical benefit in disease stabilization with use of an anti-alphaVbeta3 antibody in the settings of colorectal cancer, renal cell carcinoma, and melanoma. Integrin inhibition alone and with other targeted therapeutic approaches should be further investigated in clinical trials in patients with colorectal cancer.
整合素对刺激癌细胞增殖、防止其凋亡以及介导内皮细胞与细胞外基质之间的促血管生成相互作用具有直接作用。在已知血管生成起作用的各种癌症(包括结直肠癌)中,已观察到多种整合素及其受体的表达改变。因此,抑制特定的整合素可能会抑制整合素对癌细胞的直接作用以及肿瘤血管生成。目前,抑制性肽和抗整合素单克隆抗体正在实体瘤患者的临床试验中进行研究,早期证据表明,在结直肠癌、肾细胞癌和黑色素瘤患者中使用抗αVβ3抗体可使疾病稳定,具有临床获益。应在结直肠癌患者的临床试验中进一步研究单独使用整合素抑制剂以及将其与其他靶向治疗方法联合使用的情况。