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New Compound Overcomes Resistance to Gleevec
08 Dec 2004
A team of prominent researchers led by Charles Sawyers, MD, and Moshe Talpaz, MD, presented compelling clinical findings today showing that a new drug, BMS-354825, can successfully treat patients who have become resistant to Gleevec®, the frontline therapy for chronic myelogenous leukemia (CML).
Drs. Sawyers and Talpaz presented results of the successful Phase I clinical trial at the annual meeting of the American Society of Hematology (ASH) in San Diego, CA. Their work was financed by a Society Specialized Center of Research (SCOR) grant, which enabled them to discover the major mechanism of resistance to Gleevec and identify the compound that circumvents resistance.
The trial showed that 86 percent of the patients treated with BMS-354825, manufactured by Bristol-Myers Squibb, achieved a complete hematologic response (complete remission).
"These results are extremely promising for CML patients who develop resistance to Gleevec," said Alan Kinniburgh, Ph.D., senior vice president, Research Administration, The Leukemia & Lymphoma Society. "The Society is extremely proud to have funded the research that led to the use of BMS-354825 in this trial."
Gleevec, pioneered by Brian Druker, M.D., leader of the SCOR, was approved by the U.S. Food and Drug Administration in 2001 and has proven extremely successful in targeting cancer cells with minimal damage to normal ones. The drug inhibits the BCR-ABL protein, the hallmark of CML. But some CML patients develop resistance to Gleevec and may relapse after several months.
Dr. Sawyers was able to identify the mechanism that caused patients to become resistant to Gleevec - mutations in the BCR-ABL gene that interfere with the ability of the drug to block BCR-ABL kinase activity. In addition, the researchers uncovered BMS-354825, the compound that successfully stops the activity of the vast majority of mutations found in patients who were Gleevec-resistant.
"The identification of this compound as a drug candidate is a direct result of knowing why patients develop resistance to Gleevec," said Dr. Sawyers, of the UCLA Jonsson Cancer Center in Los Angeles, CA. "The data from this study provide compelling evidence supporting the safety and efficacy of BMS-354825."
由Charles Sawyers和 Moshe Talpaz领导的集合了众多杰出科学家的小组，发表了，现在一种新药物BMS-354825成功的治疗对Gleevec出现耐药性的慢性粒细胞白血病的患者。
Sawyers Talpaz博士，在每年一度的American Society of Hematology (ASH)会议上发表了成功的一期临床试验的结果。他们的工作是由Society Specialized Center of Research (SCOR)提供的资金，目的是使小组能够找出对Gleevec耐药的主要机制，并检验防止耐药性发生的化合物。
实验表明有86%的病人接受Bristol-Myers Squibb公司制造的BMS-354825的病人，取得了完全的血液反应（完全缓解）。
“这些结果对发生耐药的病人是非常有益的。” Alan Kinniburgh博士说，“集团非常骄傲能够资助用BMS-354825在这次试验进行研究。”
Gleevec是由Brian Druker, M.D.推出，SOCR类领先者，2001年由FDA批准上市，能非常有效的击中癌症细胞，并对正常细胞的损伤很小，该药能限制CML的标志物BCR-ABL蛋白质的量。但一些CML病人对Gleevec出现了耐药性，用药数月后出现复发（反弹）。
Sawyers博士已经摸清使病人出现对Gleevec耐药的机制，既BCR-ABL基因发生突变干扰了药物组织BCR-ABL激酶活性的能力。另外，小组发现BMS-354825，这种化合物能停止对Gleevec产生耐药的病人中发现的大量突变活动。
对作为药物候补的化合物的检验时明确为什么病人对Gleevec产生耐药的直接结果。
Sawyers说：“研究得到的数据能够提供非常有效的证据来证明BMS-354825，是完全有效的。” 站内相关链接：
BMS-354825 3期临床治疗资料
http://www.dxy.cn/bbs/post/view?bid=102&id=1930365&sty=3&keywords=BMS+354825
《Science》：BMS-354825对抗伊马替尼耐药的肿瘤细胞
http://www.dxy.cn/bbs/post/view?bid=87&id=1346131&sty=3&keywords=BMS+354825
新型ABL激酶抑制剂对伊马替尼耐药肿瘤细胞有效
http://www.dxy.cn/bbs/post/view?bid=87&id=1438876&sty=3&keywords=BMS+354825
抗白血病药物Gleevec第二代即将诞生
http://www.dxy.cn/bbs/post/view?bid=102&id=1390026&sty=3&keywords=BMS+354825
【j进展】Gleevec抗药性有了”克星”
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作者:admin@医学,生命科学 2010-10-01 17:11
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