Targeting Two Different Cancer Molecules Makes Chemotherapy More Effective
In a study published this week in the journal Cancer Discovery, scientists at the University of California, San Francisco, found that targeting two different molecules of cancer is a more effective way to shrink a tumour. This new discovery may improve the effectiveness of treatments that use different drug combinations.
The team at UCB believes that this two-target approach, which was tested in mice, may lead to the development of new therapies able to treat a wide variety of cancers. Even if clinical trials are still ongoing, this new approach may provide new hope for cancer patients.
Donald McDonald, MD, PhD, of UCSF Helen Diller member of the Comprehensive Cancer Center and the Cardiovascular Research Institute and professor of anatomy, noted that the results of the study are very promising. However, this new finding must be tested during clinical trials in order to prove its effectiveness on humans.
Up until now, studies on mice had spectacular results. Highly aggressive tumor metastasis have been reduced significantly and in some cases, metastases were eliminated completely. The two targets are two proteins known for a long time to be involved in cancer pathogenesis. The first is called c-MET, involved in cancer aggressiveness. In other words c-MET plays an important role in the process of metastasis. The second one, the vascular endothelial cell growth factor (VEGF), is a protein involved in blood vessel growth. By blocking VEGF, tumor can not normally develop its needed vascular network and consequently dies.
In 2004, the U.S. Food and Drug Administration (FDA) approved the use of such a drug to treat colon cancer, Avastin. Avastin was also approved in 2008 for use in metastatic breast cancer. However, Avastin was later revoked by the FDA arguing that this drug does not prolong survival of cancer patients.
Currently some facts about cancer progression remain unclear. For example, scientists still do not know why some tumors respond to treatment and others do not. Also, researchers do not know why a tumor responds initially and then becomes resistant to a certain treatment. In an earlier study, a team led by Douglas Hanahan, UCSF professor, found that Avastin-like drugs shrink tumors, but also increase cancer aggressiveness. This means that blocking VEGF encourages the tumor to metastasize more easily.
In their study, researchers have inhibited VEGF with two agents, the neutralizing antibody and sunitinib. c-MET was bolcked by three agents, crizotinib, PF-04217903, and cabozantinib. Surprisingly, cabozantinib inhibited both VEGF and c-MET. Simultaneous inhibition of both proteins had a more powerful effect than blocking only one protein.