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New weapon against breast cancer
iAfrica.com
2005-04-20

Breast cancer, sometimes dubbed the silent killer for its stealing of women's lives, faces a new and powerful weapon discovered by molecular biology.

A new drug that blocks a key enzyme involved in DNA repair dramatically slowed the progression of tumors in lab mice, according to research published on Thursday. The experiment has proven so successful that the first trials on humans are likely to start within months. The research targets genes called BRCA1 and BRCA2. Previous work has already shown that breast cells that have defects in these genes become timorous. Women carrying flawed versions of the two genes have up to an 85 percent chance of developing breast cancer by the age of 70.The latest work, published in the British weekly science journal Nature, pinpoints an enzyme called poly (ADP-ribose) polymerize PARP, for short that helps to fix repairs in the genetic code.

PARP's job is to identify breaks in the DNA and bind to the damaged bit of DNA, attracting specialist proteins to the site in order to make repairs. A team led by Alan Ashworth, a professor at the Institute of Cancer Research, London, found that lab-dish cancer cells with deficient BRCA1 and BRCA2 were unexpectedly and profoundly sensitive to blocking of PARP. If the PARP was inhibited, the cells became so damaged that they became unstable and eventually self-destructed. Ashworth's team took the idea further by devising a drug that blocks PARP and tested it on mice that had been injected with BRCA2-flawed tumor cells. The treatment severely blocked the cancer's progress among the rodents. But normal cells were largely unaffected by the drug, because they still possessed the correct version of the genes.

Ashworth, who helped discover the BRCA2 gene in 1995, said the PARP inhibitor works by exploiting a specific deficiency in breast cancer cells their Achilles' heel. The next step is to cautiously test the drug on humans. In the coming months, volunteers will be given the drug to see if it is safe and does not cause side effects, a press release by Ashworth's organization said. If that works, the next step will be to enrol women with BRCA-deficient tumors and test whether the drug works. Pital who was on Ashworth's team, likened the drug to a weapon aimed at a specific target, as compared to present chemotherapy, which kills timorous and normal cells alike, causing nausea and other side effects.

Targeted treatment holds considerable clinical promise, said Tutt. If our laboratory findings are confirmed in the clinic, we could dramatically improve the treatment of patients with BRCA1- or BRCA2-associated cancers. This is a completely new approach in our fight against this type of cancer. BRCA1 and BRCA2 are tumor suppressor genes. When they are mutated, they no longer suppress abnormal growth and cancer is more likely to develop. They are the best-known inherited causes of cancer but they not the only ones in this category.

In addition, only about five percent of diagnosed cases of breast cancer are attributed to a known cancer gene. Cancer can also be caused by environmental or lifestyle factors, such as smoking.

(Source: iafrica.com, April 18, 2005)

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