New developments in Breast Cancer and Cancer, from Google Alerts, for the week ending 11 July 2014.
I’ve often wondered how scientists come up with the names for these discoveries. It’s not as if TARBP2 or alpha v beta 6 trip off the tongue. I have a theory that scientists just dip their spoons into a can of alphabet soup, and whatever comes up is the name du jour … .
Something I’ve had to do this week is re-write a number of headlines. Some of the tabloids seem to view every discovery of a new oncogene or signalling pathway as a !BREAKTHROUGH! in treatment. Now that I’ve been scanning developments for more than a year, I’m more realistic. Most of these “breakthroughs” have been realised only on rodents, and they’re also years away from commercial release, plus they’re only one bit in the jigsaw puzzle that is cancer. I hate it when newspapers tout the latest cure for cancer, which is anything but.
1A. Study finds link between hyperlipidemia and breast cancer
- The European Society of Cardiology’s Frontiers in Cardiovascular Biology 2014, an event held in Barcelona, Spain in July, uncovered a link between breast cancer and hyperlipidemia.
- Apparently, those who have hyperlipidemia have a higher chance of developing breast cancer.
- Hyperlipidemia is a condition in which the body has too many lipids, or fat within the bloodstream. While lipids don’t necessarily harm a woman, they can if too large of an amount develops, as is the case with hyperlipidemia.
- The condition can cause a number of other health defects, including atherosclerosis, where a woman’s arteries become stiffer and thus cannot handle blood flow.
- Atherosclerosis, if left unchecked, can lead to a stroke or the development of heart disease. Therefore, maintaining a normal amount of lipids should be optimal.
- According to a study presented at the conference by Rahul Potluri of Aston University in the United Kingdom, he and his team found that breast cancer should be added to that above list of conditions that a woman with hyperlipidemia can develop.
- According to the Society for Vascular Surgery, women can take a number of steps to keep their cholesterol at a reasonable level and prevent the onset of hyperlipidemia.
- They should cut their fat intake to reflect only between 25-35 percent of their total calories consumed and lower their saturated fat intake to reflect only seven percent of their total calories consumed.
1B. Statins could reduce the risk of breast cancer
- Statins could be used to reduce the risk of developing breast cancer after a link between the illness and high cholesterol was established by a major study.
- Top doctors say a clinical trial to test the effect of cholesterol-busting statins on the incidence of breast cancer could happen with 10 years.
- An association between high blood cholesterol and breast cancer has been found in a study of more than one million patients over a 14 year period in Britain.
- Dr Rahul Potluri, a cardiologist at Aston University in Birmingham and the study’s lead author, said: “Our preliminary study suggests that women with high cholesterol in their blood may be at greater risk of getting breast cancer.
- “It raises the possibility of preventing breast cancer with statins, which lower cholesterol, but as this is a primitive study, significant time and research is needed before this idea can be tested.”
- A US study last year found that a cholesterol product called 27HC fuelled human breast tumours in genetically engineered laboratory mice.
- Scientists also discovered higher levels of 27HC in both healthy breast tissue and tumour cells in women with breast cancer.
2. Optimistic re-staging of breast cancers that have spread to the chest wall or skin
- Tumors that grow into the skin, regardless of size and whether they have involved lymph nodes, are automatically classified as stage III – and called “locally advanced” tumors, suggesting that they are a relatively serious form of cancer, often with poor survival.
- Fox Chase scientists cast doubt on that standard classification, by showing that women with breast cancers involving the skin have widely varied survival rates which differ by tumor size and nodal involvement.
- Within the group of tumors that have spread to the skin, there is much variety, both in size and whether or not they have spread to the lymph nodes; since these tumors occur relatively rarely, however, scientists have struggled to understand how that heterogeneity might impact survival.
- In this study, scientists looked at the SEER-Medicare Linked Database. They focused on patients age 65 or older who had been diagnosed with invasive breast cancer, and had surgery to completely remove or reduce the size of their tumors.
- Overall, stage III cancers have a 5-year survival that ranges from 41% to 67%; these results suggest that some women diagnosed with tumors that spread to the skin actually have a 96% chance of surviving 5 years, based on their tumor’s size and nodal status – similar to other early-stage tumors that have not spread to the skin.
- “Classifying all tumors with skin involvement as stage III belies the purpose of staging, which is to group tumors with a similar prognosis,” says Bleicher.
- “It makes sense that not all tumors with skin involvement behave the same. Some small, invasive tumors will spread to the skin simply because they happen to arise close to it. That doesn’t necessarily mean they will have a worse prognosis than a similar tumor that is located far enough away from the skin that it hasn’t reached it yet.”
- Based on these findings, researchers recommend adding a staging category to tumors with skin involvement, and using other criteria such as tumor size and whether or not it’s spread to lymph nodes to determine stage preferentially over skin involvement.
- Not all of these tumors should be treated the same. “For the smallest of these lesions, they may not require such aggressive treatment as chemotherapy before surgery. We need to follow a significant number of patients in that specific category before concluding how they should best be treated.”
For more information: Journal of the American College of Surgeons, DOI: http://dx.doi.org/10.1016/j.jamcollsurg.2014.04.003, Skin Involvement and Breast Cancer: Are T4b Lesions of All Sizes Created Equal?
3. Breast cancer risk may increase with a Levonorgestrel-releasing IUD
- A new study out of the journal of Obstetrics and Gynecology finds the levonorgestrel-releasing intrauterine system (LNG-IUS) or progesterone-releasing IUD, may be associated with a higher than expected incidence of breast cancer.
- This form of IUD was originally developed as a contraceptive, but later was also used as a treatment for women who suffer from heavy periods (menorrhagia) as well as endometriosis and chronic pelvic pain.
- .”The number of diagnosed new breast cancer cases among Finnish women who used LNG-IUS for menorrhagia was 19% higher than in Finnish general population,” said Dr. Tuuli Soini, the lead author of the study.However, the research does not say that this type of IUD causes breast cancer.”One limitation of our study was that women suffering from heavy menstruation may in fact represent a selected group of women who may have other risk factors for cancer, such as factors related to lifestyle, genetic factors, just to name a few.”
4. Stopping Terminator-style cell liquidity may stop metastasis
- Scientists at University College London, Kings College London, Cambridge University and Akika City University in Japan have worked out for the first time how cells are able to migrate from organ to organ.
- They discovered that cells have to change state in order to move along the narrow passages in the body.
- The links between each cell is weakened, transforming them into a liquid-like state and allowing them to invade other parts of the body.
- Vitally, the scientists also discovered the chemical signal which prompts the change.
- By switching off the signal, they were able to solidify the cells, effectively blocking any further movement.
- The research has so far only been shown to work in non-cancerous embryonic cells, but Professor Mayor of UCL is confident that it could be replicated for the way cells spread from a tumour and invade other parts of the body.
- His researchers found that a molecule called lysophosphatidic acid (LPA) was responsible for weakening the bonds between cells, allowing them to change from a solid-like to a liquid-like state and allowing them to flow between tissues in the body.
- Blocking the LPA molecules – which could be achieved through a simple injection – stopped the cells’ movement.
- ‘Our findings are important for the fields of cell, developmental and cancer biology. Previously, we thought cells only moved around the body either individually or as groups of well-connected cells. What we have discovered is a hybrid state where cells loosen their links to neighbouring cells but still move en masse together, like a liquid. Moreover, we can stop this movement.”
For more information: The Journal of Cell Biology, July 7, 2014 // JCB vol. 206 no. 1 113-127, doi: 10.1083/jcb.201402093, In vivo collective cell migration requires an LPAR2-dependent increase in tissue fluidity
5. Identified: Protein that pushes breast cancer cells to metastasize
- Scientists at Rockefeller University have identified a protein, TARBP2 that makes breast cancer cells more likely to metastasize.
- The protein appears to trigger cancer’s spread in part by blocking two other proteins that are normally linked to neurodegeneration, a finding that suggests these two disease processes could have unexpected ties.
- In order to understand what triggers cells to become malignant, scientists often look at sequences of DNA, searching for genes which are turned on or off in cancerous cells.
- But in recent years, they’ve uncovered many new mechanisms that govern cell activity, including some that act on RNA, the genetic material that helps cells make proteins using instructions encoded in DNA.
- The special strength of the researchers’ tool is that it doesn’t look simply at the sequence of RNA–it also looks at its shape.
- It turns out, the shape of an RNA molecule matters.
- Some segments of messenger RNA form hairpin loops, which create sites for key proteins to bind to and regulate that RNA – telling the cell to destroy it, for instance.
- “These structural differences help determine RNA’s fate, by exposing or hiding the binding sites for those key proteins.”
- The scientists found certain RNA hairpin loops that were over-represented in the sequences of RNAs targeted for destruction.
- They then identified a protein that binds to those hairpin sequences – TARBP2, known to play a role in the formation of small RNAs known as microRNAs.
- But here, it appears TARBP2 can also act as a “master regulator” of RNA itself, by binding to multiple sites and causing a suite of changes that lead to metastasis – including the destruction of the RNAs that carry those key binding sites.
- Indeed, they found that TARBP2 is overexpressed in cells prone to metastasizing, as well as in metastatic human breast tumors themselves.
6. Potential breakthrough treatment for Her2 breast cancer
- Researchers have identified a molecule, alpha v beta 6 (αvβ6), which helps tumours grow and spread – and which can be targeted by anti-body drugs, to eradicate tumours.
- Scientists said they believed that the treatment, in conjunction with the drug Herceptin, could help around 4,000 women a year who are diagnosed with the most aggressive type of breast cancer.
- A study examined breast cancer samples and found high levels of the molecule in 40 per cent of tumours in women with HER2 positive breast cancer, a form of the disease that does not respond to conventional hormone therapy.
- Patients with high levels of the molecule were twice as likely to die within five years of diagnosis as those with low levels, the study found.
- In experiments on mice with the same type of breast cancer, scientists used an antibody drug to block its activity.
- Combining the antibody with the drug Herceptin, which targets the cancer-driving HER2 protein, completely eradicated the animals’ tumours after six weeks of treatment, the research found.
- Using the antibody on its own reduced the size of tumours in the mice by 94.8 per cent. In comparison, treatment with Herceptin alone led to a 77.8 per cent reduction.
For more information: Journal of the National Cancer Institute, (2014) 106 (8): dju169doi: 10.1093/jnci/dju169, Therapeutic Targeting of Integrin αvβ6 in Breast Cancer
7. Potential new treatment for inflammatory/triple-negative-type breast cancer
- Inflammatory breast cancer is the most aggressive type of advanced breast cancer and is characterized by rapid development, resistance to chemotherapy, early metastases and a poor prognosis.
- Inflammatory breast cancer cells display a triple-negative breast cancer phenotype that lacks the receptors needed to promote tumor growth.
- Therefore, common treatments such as endocrine therapy and molecular targeting of the HER-2 receptor are not effective for this breast cancer subtype.
- No targeted therapy has been approved for noninflammatory and inflammatory triple-negative breast cancer tumors, and the standard of therapy for these tumors is a combination of conventional cytotoxic chemotherapeutic agents.
- Researchers used breast cancer cell lines to determine the extent to which chromosomal instability and resistance to chemotherapy — characteristics of inflammatory breast cancer — are linked to the CD44+/CD24-/Low stem-like phenotype.
- They found that CD44+/CD24-/Low cancer stem cells (CSCs) were resistant to conventional chemotherapy but were sensitive to SU9516, which is a specific cyclin-dependent kinase 2 (Cdk2) inhibitor.
- The researchers concluded from these findings that aberrant activation of cyclin E/Cdk2 oncogenic signaling is essential for maintaining and expanding the CD44+/CD24-/Low subpopulation in inflammatory breast cancer.
- Therefore, a novel therapeutic approach in inflammatory breast cancer could involve a combination of conventional chemotherapy with small-molecule inhibitors of the Cdk2 cell cycle kinase.
For more information: International Journal of Oncology, June 25, 2014, Pages: 1193-1199, DOI: 10.3892/ijo.2014.2523, Inhibition of Cdk2 kinase activity selectively targets the CD44+/CD24-/Low stem-like subpopulation and restores chemosensitivity of SUM149PT triple-negative breast cancer cells
8. New test that can predict breast cancer risk in people without BRCA mutations
- The BRCA1 gene has long been associated with the risk of breast cancer. People who have inherited mutations of this gene are reported to have an 85% risk of developing breast cancer.
- However, most people who develop breast cancer have not got a mutation of the BRCA1 gene (or the BRCA2 gene, which is similarly associated with risk). This makes it difficult to predict the risk of breast cancer among the majority of people, who have not inherited mutations of the BRCA genes.
- Now researchers have identified a set of DNA methylations that could provide a unique “signature” and potentially predict breast cancer risk in people without BRCA mutations.
- Methylation is when chemical groups attach to a gene. This does not amount to a mutation as the DNA sequence remains unchanged, but it can nevertheless alter gene activity.
- The research centred on trying to identify people who have DNA methylation of the BRCA1 gene. This means they have not inherited a mutation of the BRCA1 gene, but the gene has a methyl chemical group attached to it.
- Although the DNA sequence of the BRCA1 gene is “normal”, this methyl group addition still alters the activity of this gene.
- This laboratory research focused on examining white blood cells for DNA methylation of the BRCA1 gene, which does not alter its DNA sequence but nevertheless alters its activity.
- However, in the current study, the predictive power of this test was not very good – it was better than guessing, but not much more. Such a poor predictive accuracy could never be used as the basis of decisions about treatment. It has also only been tested in fairly small cohort samples.
For more information: Genome Medicine, 2014, 6:47 doi:10.1186/gm567, A BRCA1-mutation associated DNA methylation signature in blood cells predicts sporadic breast cancer incidence and survival
9. Junk DNA is potential new predictor of cancer
- Microsatellites are small regions of repeating DNA in the genome that can affect proper cellular function in a variety of ways.
- Researchers have discovered that microsatellite variation, can be a predictor of cancer.
- Often referred to as “junk DNA” in the past, microsatellites are currently thought to be important in a number of diseases and genetic mutations.
- Generally, mutations that occur are cleaned up by DNA repair mechanisms during replication, but not all of them are. Some of these mutations may lead to cancer.
- By using breast cancer germline (blood) samples from The Cancer Genome Atlas Project and comparing them with samples from cancer-free individuals whose genomes are found in the 1000 Genomes Project, researchers pinpointed several microsatellites that may not only reveal risks for breast cancer, but may yield therapeutic benefits, as well.
For more information: Breast Cancer Research and Treatment, June 2014, Volume 145, Issue 3, pp 791-798, Microsatellite genotyping reveals a signature in breast cancer exomes
10. DNA origami nano-tool provides important clue to cancer
- Researchers at Karolinska Institutet have headed a study that provides new knowledge about the EphA2 receptor, which is significant in several forms of cancer.
- The researchers used the method of DNA origami, in which a DNA molecule is shaped into a nanostructure, and used these structures to test theories about cell signalling.
- It was previously known that the EphA2 receptor played a part in several forms of cancer, such as breast cancer.
- The ligand, i.e., the protein that communicates with the receptor, is known as an ephrin molecule.
- Researchers have had a hypothesis that the distance between different ligands – in this case the distance between ephrin molecules – affects the level of activity in the communicating receptor of the adjacent cells.
- The Swedish researchers used DNA building blocks to form a stable rod.
- This rod was then used as a very accurate measure of the distance between molecules.
- The researchers attached proteins, or ephrins, to the DNA rod at various intervals, for example 40 or 100 nanometres apart.
- The DNA rods were then placed in a solution containing breast cancer cells. In the next step, the researchers looked at how active EphA2 was in these cancer cells.
- It turned out that if the ephrin molecules were placed close together on the DNA rod, the receptor in question became more active in the cancer cells, and the cells also became less invasive in respect of the surrounding cells, which could be an indication that they became less prone to metastasis.
- This was true even though the amount of protein was the same throughout the experiments, i.e., the number of attached molecules remained the same.
- “For the very first time, we have been able to prove this hypothesis: the activity of EphA2 is influenced by how closely spaced the ligands are on the surrounding cells”, says Björn Högberg.
- “This is an important result in itself, but the point of our study is also that we have developed a method for examining how cells react to nearby cells in a controlled environment, using our custom DNA nano-calipers.”
- The researchers describe the cell communication as a form of Braille, where the cells somehow sense the protein patterns of nearby cells, and where the important thing is not only the amount of proteins, but to a great extent the distance between them as well.
- This study found that a cluster of proteins would communicate more actively than sparsely spaced proteins, even if the concentration was the same.
For more information: Nature Methods, online July 6 2014; DOI: 10.1038/nmeth.3025, Spatial Control of Membrane Receptor Function using Ligand Nano–Calipers