Receptor tyrosine kinase (c-Kit) inhibitors: a potential therapeutic target in cancer cells

被引:194
作者
Babaei, Maryam Abbaspour [1 ]
Kamalidehghan, Behnam [2 ,3 ]
Saleem, Mohammad [4 ,5 ,6 ]
Huri, Hasniza Zaman [1 ,7 ]
Ahmadipour, Fatemeh [1 ]
机构
[1] Univ Malaya, Fac Med, Dept Pharm, Level 3,Block R, Kuala Lumpur, Malaysia
[2] NIGEB, Dept Med Genet, Km 15,POB 14965-161, Tehran, Iran
[3] Shahid Beheshti Univ Med Sci, Sch Med, Med Genet Dept, Tehran, Iran
[4] Univ Minnesota, Masonic Canc Ctr, Dept Urol, Austin, MN USA
[5] Univ Minnesota, Masonic Canc Ctr, Dept Lab Med & Pathol, Austin, MN USA
[6] Hormel Inst, Sect Mol Therapeut & Canc Hlth Dispar, Austin, MN USA
[7] Univ Malaya, Med Ctr, Clin Invest Ctr, Kuala Lumpur, Malaysia
关键词
c-Kit; cancer; oncogene; cancer therapy; GASTROINTESTINAL STROMAL TUMOR; SRC FAMILY KINASES; POINT MUTATION; SIGNAL-TRANSDUCTION; INTERSTITIAL-CELLS; CATALYTIC DOMAIN; THYMIC CARCINOMA; GENE-MUTATIONS; GROWTH-FACTOR; SYSTEMIC MASTOCYTOSIS;
D O I
10.2147/DDDT.S89114
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
c-Kit, a receptor tyrosine kinase, is involved in intracellular signaling, and the mutated form of c-Kit plays a crucial role in occurrence of some cancers. The function of c-Kit has led to the concept that inhibiting c-Kit kinase activity can be a target for cancer therapy. The promising results of inhibition of c-Kit for treatment of cancers have been observed in some cancers such as gastrointestinal stromal tumor, acute myeloid leukemia, melanoma, and other tumors, and these results have encouraged attempts toward improvement of using c-Kit as a capable target for cancer therapy. This paper presents the findings of previous studies regarding c-Kit as a receptor tyrosine kinase and an oncogene, as well as its gene targets and signaling pathways in normal and cancer cells. The c-Kit gene location, protein structure, and the role of c-Kit in normal cell have been discussed. Comprehending the molecular mechanism underlying c-Kit-mediated tumorogenesis is consequently essential and may lead to the identification of future novel drug targets. The potential mechanisms by which c-Kit induces cellular transformation have been described. This study aims to elucidate the function of c-Kit for future cancer therapy. In addition, it has c-Kit inhibitor drug properties and their functions have been listed in tables and demonstrated in schematic pictures. This review also has collected previous studies that targeted c-Kit as a novel strategy for cancer therapy. This paper further emphasizes the advantages of this approach, as well as the limitations that must be addressed in the future. Finally, although c-Kit is an attractive target for cancer therapy, based on the outcomes of treatment of patients with c-Kit inhibitors, it is unlikely that Kit inhibitors alone can lead to cure. It seems that c-Kit mutations alone are not sufficient for tumorogenesis, but do play a crucial role in cancer occurrence.
引用
收藏
页码:2443 / 2459
页数:17
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