Breast cancer probably is the most common cancer in the UK and affects around 46,000 women every year. Though anti-oestrogen drugs like tamoxifen serve as an apt treatment for this form of cancer, most patients may develop resistance to these medications. Well, researchers have now laid hands on a novel protein that is involved in the development of drug resistance in breast cancer. This protein can supposedly serve as a target for new treatments.
A mouse model of breast cancer was put to use for blocking production of the protein. Scientists used genetic techniques to shrink tumors and are now hunting for drugs that could achieve a similar effect. This protein called LMTK3 was seemingly blocked within human cancer cells that were resistant to tamoxifen. When genetic techniques were utilized for blocking the production of LMTK3, a significant decrease in the size of breast tumors was reported.
“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. 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,” shared Professor Justin Stebbing, from the Department of Surgery and Cancer at Imperial College London, the senior researcher.
Not only that, investigators also measured levels of LMTK3 in tissue samples taken from women with breast cancer. Those with higher levels of LMTK3 in their tumors were probably more inclined to live less long and were also less likely to respond to hormone therapy. Certain mutations in the gene coding for LMTK3 were apparently associated with the survival of a patient.
“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,” said Dr Georgios Giamas, who designed and led the research, from the Department of Surgery and Cancer at Imperial College London. “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.”
Experiments conducted in the lab revealed that resistance to hormone therapy occurs when the oestrogen receptor is modified by enzymes called kinases. LMTK3 is believed to be a favorable treatment target for kinases that affect how cancer cells respond to oestrogen. DNA sequences in the gene coding for LMTK3 in humans was compared to that of chimpanzees, probably because chimpanzees are not susceptible to oestrogen receptor positive breast cancer. Substantial differences that have evolved in these sequences between the two species were registered.
The research is published in the journal Nature Medicine.