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癌症干细胞可能导致药抗性和肿瘤转移

2014年04月25日

长期以来癌症疗法在临床上都是一把双刃剑。如果对肿瘤置之不理,则会威胁患者生命,另一方面抗癌药物的使用却会导致抗药性的产生并最终造成肿瘤的“百毒不侵”。

最近来自美国加州大学圣迭戈分校的研究人员发现一种名为CD61的肿瘤表面蛋白分子可能与肿瘤的抗药性和肿瘤迁移有关,这一结果被发表在 Nature Cell Biology。负责这项研究的 David Cheresh介绍说,他们研究发现肿瘤发生过程中,癌细胞会获得类似干细胞的特性,同时也会导致癌细胞对药物的抗性,David Cheresh等人的成果探明了这一机制的分子通路。利用这一发现加州大学的Dr. Hatim Husain设计了一种新型疗法以治疗抗药性肺癌。这一研究将于明年正式启动。

详细英文报道:

Treating some cancers is a double-edged sword. On one hand, cancers can grow and spread when left untreated. On the other hand, many drugs used to treat lung, breast and pancreatic cancers also promote drug resistance and can ultimately spur tumor growth.

Now, researchers may be able to predict which individual tumors will metastasize and spread when treated with certain drugs. Scientists at the University of California, San Diego School of Medicine have discovered a biomarker on the surface of drug-resistant tumors that could eventually help physicians reverse drug resistance in cancers and improve treatment outcomes in patients.

The marker, a molecule called CD61, was detected on the surface of drug-resistant tumors and appears to be responsible for inducing tumor metastasis by enhancing the stem cell-like properties of cancer cells. The findings appeared online April 20 in Nature Cell Biology.

Sometimes, patients respond to an initial cancer treatment but then relapse when cancer cells become drug-resistant. To find out what changes in those cancer cells, David Cheresh, a distinguished professor of pathology at UC San Diego, and his colleagues investigated how tumor cells become resistant to standard cancer drugs like erlotinib or lapatinib. They found that as drug resistance occurs, tumor cells acquire stem cell-like properties that give them the ability to thrive in the body and become unaffected by the drugs.

The investigators pinpointed the molecular pathway that accelerates both cancer stemness and drug resistance, and identified existing drugs that work in this pathway to reverse the stem cell-like properties of tumors as well as resensitize tumors to drugs.

Using these findings, Dr. Hatim Husain, an assistant professor who treats lung and brain cancer patients at UC San Diego's Moores Cancer Center, has designed a clinical trial to home in on this pathway in patients with drug-resistant tumors.

The trial, which is expected to begin within the next year, will enroll lung cancer patients who have experienced cancer progression and drug resistance to erlotinib. Though the trial will initially enroll patients who have already experienced drug resistance, Husain hopes to extend the study to reach patients in earlier stages to prevent initial drug resistance.