According to researchers, they prevent the growth of cancer cells

A new type of therapy can help to effectively treat breast cancer, reported biologists from the University of Aberdeen. It's about the application of the specific type of antibody IgNAR (immunoglobulin new antigen receptor), which are found in cartilage fish - such as sharks. According to researchers unique antibody can prevent the growth of cancer cells.

Over the next three years is to provide a number of studies that confirm the theory and help to create a cure for the most common malignancy in women location. Scientists will focus on the two molecules - HER2 and HER3, which are arranged on the surface of cancer cells. When these molecules are combined, the cancer cells receive signals for growth and division. According to researchers IgNAR can stop the transmission of the signal and to prevent progression of the disease.

Two recent studies by CRG researchers delve into the role of chromatin modifying enzymes and transcription factors in tumour cells.

In one, published on September 9 in Genes & Development, it was found that the PARP1 enzyme activated by kinase CDK2 is necessary to induce the genes responsible for the proliferation of breast cancer cells in response to progesterone. In addition, extensive work has been undertaken to identify those genes activated by the administration of progesterone in breast cancer, the sequences that can be recognised and how these genes are induced. This work will be published on November 21 in the journal Molecular Cell.

Cancer is a complex set of diseases and only thanks to advances in genomic techniques have researchers begun to understand, at a cellular and molecular level, the mechanisms which are disrupted in cancer cells, a prerequisite for developing effective strategies to treat these diseases.

One clear example of this is breast cancer. It has long been known that hormones such as estrogen and progesterone encourage the proliferation of cancer cells. Because of this, one of the most common treatments is the administration of hormone receptor blockers. The block, however, affects all the cells of the body not only the cancer cells, and causes a number of side effects in patients. Additionally, most cancers develop resistance after a time and continue to grow despite anti-hormone therapy. To treat these patients it is necessary to understand the mechanisms that trigger the proliferation, which will allow their direct inhibition.

The scientists from the Cromatin and Gene Expression lab at the CRG, led by Miguel Beato, are dedicated to understanding how hormones activate cell division in breast cancer, focusing on regulating the expression of the genes that control the cell cycle.

Hormone receptors are transcription factors that bind to DNA sequences in the vicinity of the genes they regulate. But the DNA of the genes is packed into a dense structure known as "chromatin," which is considered a barrier preventing the access of transcription factors to genes. Therefore the chromatin must be decompacted for the transcription factors to activate the target genes expressed in RNA and subsequently translate them into proteins that stimulate cell proliferation. This is where the progesterone, via its receptor, activates various enzymes initiating chromatin opening.

In the study published on September 1 in the journal Genes & Development, the researchers looked at the role of an enzyme, PARP-1, which is primarily responsible for the repair of cuts in DNA. "It was not known how PARP-1 is activated and we found that it happens via the activation of another enzyme, CDK2, which phosphorylates and activates PARP-1, which in turn modifies the histone H1 and the chromatin displacement. And if PARP1 does not do this, many of the progesterone's target genes are not regulated," explains Roni Wright, first author of the study. Wright is a postdoctoral researcher in Beato's lab. She believes that much remains to be discovered in this area of research. "This experiment was conducted on cell lines, but now we have to do it on real, patient cells to see if their behaviour is the same," adds the researcher.

How do we know how the proliferation of cancer cells is controlled?

Gene regulation (how genes activate and deactivate) is the key to the overall understanding of how our genome works and when this function is altered. "It is important to discover the mechanism by which genes are activated around chromatin," explains Miguel Beato, head of the Chromatin and Gene Expression group. The chromatin packs the DNA at several levels, the first being the "nucleosomes," which help stabilise the DNA chain. "It was thought that the chromatin structure was not relevant to explaining how genes turn on and off, but we have discovered that it is crucial," adds Beato.

The second study, published online on November 21, 2012 in the journal Molecular Cell, addresses this issue. Firstly, all the genes that progesterone activates or represses in breast cancer cells were identified. Then the researchers identified which DNA sequences recognise the progesterone receptor in the genome. They found that these represented only a small proportion of the possibilities, making them think that interaction with DNA was not sufficient. It was necessary for the sequences which bind to the receptor to be incorporated into nucleosomes, which also provide interaction sites. "It seems that chromatin has a lot to do with determining which genes are activated and which are not," says Cecilia Ballaré, first author of this second paper.

The researchers believe that the only way to create increasingly specific and effective cancer treatments is by studying the role of all the elements that regulate gene expression and cell proliferation in response to hormones. "Knowing the exact way progesterone affects the proliferation of cancer cells may help develop more specific treatments that fight only cancer cells and thus produces fewer side effects," adds Ballaré.

According to a report published in the Annals of Oncology, women with Herr-2 positive breast cancer who received trastuzumab as adjuvant therapy are at significantly increased risk of metastases in the central nervous system as a first recurrence of the tumor.

According to Dr. Erin Olson, a neurologist at Ohio State University and author of the study, trastuzumab significantly reduced the risk of recurrence, but clinicians should be aware that it increases the risk of them occur in the nervous system. Physicians should carefully monitor patients for neurologic symptoms.

It is suggested that the nervous system is the "refuge" for micro metastatic tumors because trastuzumab does not cross the blood-brain barrier or because tumor cells that do not overexpress Herr-2 receptor migrate more easily into the brain.

In previous studies, Dr. Olson and her team showed that anti Herr-2 targeted therapies increase the frequency of brain metastases. This spurred her to investigate the relationship between brain metastases and trastuzumab. The team analyzed four Phase III clinical trials with a total of 9,020 participants.

Since 4921 women receiving trastuzumab, 125 relapse in the breast (incidence of 2.56%). Of 4099 women who received trastuzumab, 78 relapse of the tumor in the brain (1.94%). In patients treated with trastuzumab treatment brain metastases / total metastases is 16.94 / 100, while those treated with other adjuvant is 8.33 / 100.