Malignant melanoma cannot grow without a steady supply of a protein that is not essential for normal cells, a finding that may lead to a new, effective therapy with relatively low toxicity, according to an article in the December issue of Cancer Cell.

Working with melanoma cells grown in the laboratory, the researchers, led by David E. Fisher, MD, PhD, the paper’s senior author, showed that adding a chemical that quashed the activity of CDK2, the gene that manufactures CDK2 protein, dramatically slowed growth and proliferation of the cancer cells. Unlike conventional chemotherapy drugs, a CDK2 inhibitor drug wouldn’t be aimed at killing melanoma cells, only halting their continued growth.

Fisher said that CDK2-inhibiting drugs exist, and he hopes that the research results will soon lead to clinical trials of them in patients with melanoma. The study’s lead author is Jinyan Du, PhD, who carried out the project while working as a student in Fisher’s lab at the Dana-Farber Cancer Center.

The CDK2 gene and the enzyme it encodes are one of several regulators of the cell cycle:. Overactive CDK2 has been found in many types of cancer, making it a prime candidate for drugs that would decrease CDK2 activity and slow ongoing proliferation of cancerous cells. However, recent studies have found that many of these tumors are not dependent on CDK2 for growth.

The current report is all the more striking because it reveals that melanoma does require the CDK2 enzyme for growth. Because it has been previously shown that normal cells can divide and grow normally without CDK2 (other types of CDK molecules apparently assume the regulatory role) “this is good news, because it means there may be little toxicity to a person who would receive a CDK2 inhibitor to treat melanoma,” said Fisher.

The new findings stem from Fisher’s longtime work on a gene called MITF that regulates the development of skin pigment-producing cells called melanocytes. Regulatory genes like MITF act on other genes in a chain-of-command fashion. When Fisher’s group looked for genes regulated by MITF, they found a pigment gene called SILVER, and they noted that, surprisingly, it was located very close to the gene for CDK2 on the chromosome.

“It was dumb luck,” said Fisher, and it led him and his colleagues to recognize that both SILVER and CDK2 were under the control of MITF. In all other body cells besides melanocytes, CDK2 is not subservient to MITF: To the researchers this was an important clue.

“If the control of CDK2 expression is so different in the development of melanocytes, then maybe the requirement for CDK2 in melanoma is different than in other cancers,” he hypothesized - and the new findings confirm this idea.