Drugs most commonly used to treat breast, lung, and pancreatic cancers eventually become ineffective and actually encourage drug-resistance and tumor growth through the development of cancer stem cells. A new study from the University of California, San Diego (UCSD) has found that cancer tumor cells develop properties similar to stem cells, which enable them to develop drug-resistance and survive throughout the body. The findings, which were published today in the journal Nature Cell Biology, may point to new treatment opportunities that will reverse drug resistance in a variety of cancers.
Senior study author David Cheresh says that many patients relapse as cancer cells become drug-resistant. The study looked at the cells both before and after the drug-resistance developed, to try to identify what had changed. They found that as drug-resistance happens, tumor cells develop stem cell-like properties that allow them to survive throughout the body, despite the presence of treatment drugs.
Cancer stem cells, which cause tumors to grow, are similar to embryonic stem cells because they proliferate and spread throughout the body. The research discovered a molecular marker called CD61 on the surface of these cells, which causes them to remain in a stem-like state. Researchers are looking for drugs that act against this CD61 molecule. It would appear that some drug-resistant cancers might be made open to treatment with a medication that is already used for treating another type of cancer.
The drug Velcade is already approved for treatment of relapsed multiple myeloma. Laboratory studies showed that Velcade also seems to resensitize cancer cells that had become resistance to another drug called Tarceva. Tarceva is part of a class of cancer drugs that cancer stem cells selectively resist. It is commonly used to treat some lung and pancreatic cancers. The studies found that Velcade reversed cancer stem cell properties and drug-resistance, restoring Tarceva’s effectiveness.
The UCSD researchers plan to start a clinical trial testing Velcade for treating lung cancer. For the upcoming trial, patients will get a combination of Velcade and Tarceva. Cheresh says the timing is important to achieve maximum effects from the therapy. He says it does not make sense to use Velcade before resistance to Tarceva has developed, because the more the cancer has mutated to resist treatment the more effective Velcade will be at reversing the cancer stem cell properties.
Now that the CD61 molecule has been identified, scientists can determine when a tumor is becoming stem-like and resistant, so that they can intervene earlier. They are working on a blood test for determining ,as early as possible ,when the stem cell conversion happens.
Dr. Hatim Husain, the study author who is designing the clinical trial, says that the more proven combination drug therapies are available, the more doctors will be successful in keeping cancer in check. He says their goal is to make it something like diabetes.
According to the Winship Cancer Institute’s deputy director, Dr. Fadlo R. Khuri, the researchers’ findings are significant. He says their work has identified an important biologic feature of cancer stem cells, which are the tumor initiating cells that become drug resistant.
By Beth A. Balen