Oudard S, Marie J P, Pujade Lauraine E
Service d'oncologie médicale, Hôtel-Dieu, Paris, France.
Bull Cancer. 1996 Aug;83(8):609-18.
Multifactorial resistance is the main mechanism of chemotherapy failure in cancers. Multidrug resistance (MDR) is related to the expression of a 170 kDa membrane glycoprotein, the so-called P-glycoprotein (P-gp). This protein is able to extrude drugs of various structures and mechanisms out of the cytoplasm. P-gp is a pronostic value in hemopathy as well as in child sarcoma, osteosarcoma and neuroblastoma. Modulator agents of different generations are capable of inhibiting P-gp. MDR modulation is obtained in hemopathies and is associated with an eradication of the P-gp (+) cell clones. In solid tumors, clinical trials using verapamil or cyclosporin are not so convincing. It is likely that other mechanisms of resistance are responsible for tumor progression, such as the MRP system, glutathion and topoisomerases. A better knowledge of multifactorial resistance and drug synthesis counteracting these resistance mechanisms will allow to elaborate new therapeutic basis for cancer therapy.
多因素耐药是癌症化疗失败的主要机制。多药耐药（MDR）与一种170 kDa的膜糖蛋白即所谓的P-糖蛋白（P-gp）的表达有关。这种蛋白质能够将各种结构和机制的药物排出细胞质。P-gp在血液病以及儿童肉瘤、骨肉瘤和神经母细胞瘤中具有预后价值。不同代的调节剂能够抑制P-gp。在血液病中可实现MDR调节，且与P-gp（+）细胞克隆的清除有关。在实体瘤中，使用维拉帕米或环孢素的临床试验并不那么令人信服。可能还有其他耐药机制导致肿瘤进展，如多药耐药相关蛋白（MRP）系统、谷胱甘肽和拓扑异构酶。更好地了解多因素耐药以及对抗这些耐药机制的药物合成将有助于为癌症治疗制定新的治疗基础。
