What if the best way to stop a tumor is not to kill it, but to turn it into something else? That’s the idea behind differentiation therapy, a novel concept that targets cancer stem cells. Scientists at Sanford-Burnham and elsewhere are beginning to think that stem cells may be the culprit behind tumor formation in some cancers. Much like other types of stem cells, cancer stem cells are presumably able to do two things: 1) self-renew, generating more new stem cells and 2) differentiate, giving rise to a variety of cell types. Differentiation therapy attempts to end the cycle of self-renewal by encouraging the cells to settle down and become a specific cell type, such as a skin cell.
“It seems to me that if we are smart enough to know all the genes in a cell, we should be smart enough to tell the cell what to do,” says Dr. Robert Oshima, co-director of the Sanford-Burnham Cancer Center’s Tumor Development Program. “In differentiation therapy, we are essentially telling cells: ‘Don’t become criminals, become productive members of society. If you stay legal, we’ll leave you alone.’”
In collaboration with associate professor Dr. Masanobu Komatsu and others, Dr. Oshima led a recent study that provides strong evidence in favor of differentiation therapy. In the study, which was published online today by the journal Oncogene, an aggressive mouse model of breast cancer was treated with Bosutinib (SKI-606), a drug currently being developed by Pfizer Research to treat advanced malignant tumors.
What resulted from Bosutinib treatment? Perhaps not surprisingly, the drug prevented the appearance of tumors in more than half of the treated mice and reduced tumor growth in older animals with preexisting tumors. The real shocker was the reason these tumors stopped growing. Bosutinib treatment was successful not because it directly killed the cancer cells, but because it induced their differentiation. In other words, tumors in the treated mice experienced another fate; they contained a lot of normal, functioning tissue not seen in the untreated mice. These benign tissues behaved like normal skin cells or milk-producing cells of the mammary gland rather than as undifferentiated cancer stem cells.
Differentiation therapy is an attractive alternative to chemotherapy and radiation, which kill any cell whether cancerous or not. According to Dr. Oshima, “Older treatments for cancer are almost as bad as the disease. Cancer cells are simply poisoned or burned, while doctors try their best to limit the side effects by reducing the collateral damage to other tissues.”
Dr. Oshima and his team are now searching for other drugs that might induce cancer stem cell differentiation in order to stop tumors at their earliest stages.
“The ultimate dream would be to design a pill that high-risk women take just once a year to prevent breast tissue stem-like cells from becoming breast cancer,” said Dr. Oshima.