Identification of RET kinase inhibitors as potential new treatment for sporadic and inherited thyroid cancer

被引：24

作者：

Carlomagno, F ^{[1
]}

Santoro, M ^{[1
]}

机构：

[1] CO Dipartimento Biol & Patol Cellulare & Mol, Univ Naples Federico II, Fac Med & Chirurg, Ist Endocrinol & Oncol Sperimentale,CNR, I-80131 Naples, Italy

来源：

JOURNAL OF CHEMOTHERAPY | 2004年 / 16卷

关键词：

RET kinase inhibitors; thyroid cancer; pyrazolo-pyrimidine; anilinoquinazoline;

D O I：

10.1179/joc.2004.16.Supplement-1.49

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The RET gene is frequently mutated in papillary thyroid carcinoma and in medullary thyroid carcinoma. We have identified three different anti-RET drugs: two pyrazolo-pyrimidines, PP1 and PP2 and an anilinoquinazoline, ZD6474 (AstraZeneca). These compounds are able to inhibit RET kinase activity in vitro (IC50 dose 100 nM) and in vivo and they can prevent RET mediated transformation. Finally, mutation of RET V804 to methionine or leucine, found in MTC patients, induces resistance to the three drugs.

引用

页码：49 / 51

页数：3

共 4 条

[1]

Carlomagno F, 2002, CANCER RES, V62, P7284

[2] Efficient inhibition of RET/papillary thyroid carcinoma oncogenic kinases by 4-amino-5-(4-chloro-phenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) [J].

Carlomagno, F ;

Vitagliano, D ;

Guida, T ;

Basolo, F ;

Castellone, MD ;

Melillo, RM ;

Fusco, A ;

Santoro, M .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2003, 88 (04) :1897-1902

[3]

Carlomagno F, 2002, CANCER RES, V62, P1077

[4] Functional expression of the CXCR4 chemokine receptor is induced by RET/PTC oncogenes and is a common event in human papillary thyroid carcinomas [J].

Castellone, MD ;

Guarino, V ;

De Falco, V ;

Carlomagno, F ;

Basolo, F ;

Faviana, P ;

Kruhoffer, M ;

Orntoft, T ;

Russel, JP ;

Rothstein, JL ;

Fusco, A ;

Santoro, M ;

Melillo, RM .

ONCOGENE, 2004, 23 (35) :5958-5967

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