New Compound Shrinks Skin Cancers

Some 1 million Americans get basal cell carcinoma each year. It often doesn't spread but, once it has, there are no approved treatments. Medulloblastoma is an aggressive form of brain tumor.

The first trial enrolled 33 individuals whose basal cell carcinoma had spread locally or to distant organs.

Half of the participants who had distant metastases saw a reduction in tumor size, as did 60 percent of those with locally advanced cancer. The rest had either stable or progressive disease after 10 months of follow-up.

But "stable" in this population may not mean much, Perlis pointed out, as it is generally a very slow-growing cancer.

The man with medulloblastoma also saw a significant shrinkage of his tumor, along with vastly improved quality of life, but only for two months. He later died.

A third study by some of the same authors, this one published online Sept. 2 in Science Express, discovered that treatment with GDC-0449 actually spurred another mutation in a gene called SMO, which caused the brain tumor to become resistant to the drug.

Because the Hedgehog pathway does not actually do much in adults, side effects were minimal, said de Sauvage.

GDC-0449 would likely be used very differently, depending on which type of cancer it is targeting.

In the case of basal cell carcinoma and medulloblastoma, the mutation in the Hedgehog pathway "really drives the formation of these tumors," de Sauvage said. "This molecule inhibits the pathway very specifically and, to date, we only know of these two types of tumor where the pathway is mutated." That means GDC-0449 is effective on its own.

But in colon and ovarian cancer, he continued, the pathway recruits surrounding cells to promote the cancer. In these types of tumors, GDC-0449 would have to be combined with other drugs.

More information

The American Academy of Dermatology has more on basal cell carcinoma.

SOURCES: Clifford Perlis, M.D., director, Mohs Micrographic Surgery and Dermatologic Surgery, Fox Chase Cancer Center, Philadelphia; Andrzej Dlugosz, professor, department of dermatology, University of Michigan Medical School and Comprehensive Cancer Center, Ann Arbor; Frederic de Sauvage, Ph.D., vice president, research, molecular biology, Genentech; Charles M. Rudin, M.D., Ph.D., associate director, clinical research, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore; Sept. 2, 2009, New England Journal of Medicine, online; Sept. 2, 2009, Science Express, online

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