May 24, 2011

Blocking Protein to Help Fight Cancer?

(Ivanhoe Newswire) -- Researchers have just recognized a novel protein involved in the development of drug resistance in breast cancer, which could be a target for new treatments.

In a mouse model of breast cancer, blocking production of the protein via genetic techniques caused tumors to get smaller. Scientists are currently searching for innovative drugs, which could accomplish a comparable effect.

Breast cancer is the most frequent cancer in the UK, affecting approximately 46,000 women each year.  More than two thirds of breast tumors contain oestrogen receptors, meaning that they need the hormone oestrogen to develop, and they can be treated with anti-oestrogen drugs such as tamoxifen.  Nonetheless, numerous patients build up resistance to these treatments so that the drugs sooner or later cease to be effectual.

In today's study, researchers from Imperial College London discovered that blocking a protein known as LMTK3 in human cancer cells that were defiant to tamoxifen made the cells more receptive to the drug.  In a mouse model of the disease, by means of genetic techniques to block the making of LMTK3 led to a noteworthy reduction in the size of breast tumors.

Researchers furthermore measured levels of LMTK3 in tissue samples taken from women with breast cancer.  They established that women who had higher levels of LMTK3 in their tumors tended to live less long and were less likely to act in response to hormone therapy.  In addition, they discovered that particular mutations in the gene coding for LMTK3 was additionally interrelated with how long a patient would survive.

"Anti-oestrogen drugs have been very successful at allowing women with breast cancer to live longer, but resistance to these drugs is a common problem," which Professor Justin Stebbing, from the Department of Surgery and Cancer at Imperial College London, the study's senior author, was quoted as saying.  "Our results suggest that the action of LMTK3 on the oestrogen receptor has a crucial role in the development of drug resistance.

"We're now looking for drugs that can block the effect of LMTK3, which we could hopefully give to patients to prevent them from becoming resistant to hormone therapy.  It will probably take at least five to ten years to develop new treatments that are safe to be used in humans."

Confirmation from the laboratory suggests that resistance to hormone therapy might take place when enzymes called kinases modify the oestrogen receptor.  The team recognized LMTK3 as a possible treatment target by screening for kinases that affect how cancer cells react to oestrogen.

The researchers additionally compared DNA sequences in the gene coding for LMTK3 in humans and chimpanzees, for the reason that chimpanzees are not vulnerable to oestrogen receptor positive breast cancer.  They found that considerable differences have evolved in these sequences between the two species.

"It's quite intriguing that humans and chimps have evolved these differences in the LMTK3 gene, since related genes are very similar between the two species," which Dr. Georgios Giamas, who designed and led the study, from the Department of Surgery and Cancer at Imperial College London, was quoted as saying.

"We could speculate that evolutionary changes in this gene might have given humans some unknown advantage, but also have made us more susceptible to breast cancer."

SOURCE: Nature Medicine, May 22, 2011