Researchers have come u with a new treatment strategy to combat cancer. Researchers at the University of Michigan Comprehensive Cancer Centre have discovered that pushing the cancerous cells into over drive results in their self-destruction.
And this is possible by using bortezomib, a promising cancer drug, which helps to strike a blow against melanoma tumour cells by revving up the action of a cancer-promoting gene. Researchers discovered that bortezomib, a drug approved by the FDA to treat advanced multiple myeloma, is able to selectively inhibit melanoma tumour cells because it causes the c-MYC oncogene to overproduce a cell-death promoter called NOXA.
Their findings place c-MYC and NOXA, well studied among cancer researchers, in a new light. "Our data suggest a different approach to treat cancer," said Maria S. Soengas, Ph.D., the senior author of the study. Many cancer treatments aim to block specific oncogenes, genes that wreak havoc with the normal signals that dictate when cells multiply and die.
Melanoma tumour cells manage to resist most cancer drugs. For more than 30 years, the prognosis for patients with advanced melanoma has not significantly improved. Soengas likens the melanoma tumour cell's defenses to a heavy suit of armor that so far has blocked researchers' attempts to penetrate it. Now it appears that the tumour cells have an enemy within.
In human melanoma cells cultured and manipulated in the laboratory, the research team studied bortezomib and other drug candidates to understand their molecular modes of action. Bortezomib belongs to a class of drugs called proteasome inhibitors that show promise in attacking many types of tumours. But how the drugs direct their biggest punch at tumour cells, with less effect on normal ones, has puzzled scientists - the cell actors they target, proteasomes, are widespread and essential to normal cells.
The research team reported in 2005 that bortezomib appears to combat tumour growth by increasing the activity of a cell-death promoter called NOXA in tumour cells, but not in normal cells. In the new study, they report that the force behind this selective uptick in NOXA, and the resulting cell death, surprisingly turned out to be the oncogene c-MYC.
Mikhail Nikiforov, Ph.D., the paper's first author, said that the discovery of the oncogene's role in bortezomib's action has implications for other cancers besides melanoma. The Soengas and Nikiforov groups collaborated to elucidate molecular mechanisms of c-MYC-mediated regulation of NOXA in melanoma and other tumour cell types.
Soengas said that the findings lay the groundwork for more studies to improve bortezomib's effectiveness in treating cancers and to reduce its toxicity in normal cells. "Now we can rationally design drugs that enhance bortezomib's action and favor NOXA production. Improvements might make it possible to give lower doses of the drug for a shorter time," she said.
The study appears online ahead of print in the Proceedings of the National Academy of Sciences.