A summary of news for the week ending 11 April 2014 from Google Alerts – Breast Cancer and Cancer. Sometimes I feel as if this whole cancer-fighting business is like a bad B-horror-movie. There were two articles this week which made me marvel about how ingenious and indestructible cancer cells appear to be.
The first is a study which showed how cancer cells eat themselves at times of stress and come back to life … just like zombies. The second is research which shows how different types of cancer cells can cooperate to grow tumours. It’s almost like cancer cells have an intelligence and life of their own, and aren’t just rogue cells.
The more I investigate, the more I realise why cancer is such a badass to deal with.
On a positive note, even zombies can be killed … we just have to be smarter to outwit them. And you know how in movies where zombies are blasted to pieces with an anti-zombie gun that’s invented by the wacky scientist … well, there’s been research into using magnetic nanoparticles that get eaten up by cancer cells and which then explode when exposed to magnetic fields!
There was an article on how copper can fuel the growth of tumours, so removing it from the body could starve the tumours. This is not a new development, as a reader, J, has pointed out – please refer to the comments and see the studies that J has sent, dating from 2000. It’s such a shame that this information has been around, but the treatment is not part of standard-of-care.
There’s been a glut this week in new developments and drugs (and I apologise for using the zombie article which is admittedly sensationalist) … I was intrigued by the blip, until I realised that it’s the American Association for Cancer Research’s annual meeting in San Diego which was held this week – so tune in for more amazing anti-zombie cures in the weeks to come!
1. Zombie cancer cells eat themselves to live
- The cellular process of autophagy in which cells “eat” parts of themselves in times of stress may allow cancer cells to resurrect themselves rather than die when faced with chemotherapies.
- A movie that accompanies the study online shows a cancer cell dying. In the first few frames, mitochondrial cell walls break down and the cell’s mitochondria can be seen releasing proteins in a process abbreviated as MOMP, which is considered a common marker of cell death.
- But then high autophagy allows the cell to encapsulate and “digest” these released proteins before MOMP can keep the cell well and truly dead.
- Later in the movie, the cancer cell recovers and goes on to divide.
- The implication here is that if you inhibit autophagy you’d make this less likely to happen, i.e. when you kill cancer cells they would stay dead.
- The finding has important implications
- First, it demonstrates a mechanism whereby autophagy controls cell death.
- Second, the study further reinforces the clinical potential of inhibiting autophagy to sensitize cancer cells to chemotherapy.
For more information: Cell Reports, Vol. 7, Issue 1, p45–52, DOI: http://dx.doi.org/10.1016/j.celrep.2014.02.036, Autophagy Controls the Kinetics and Extent of Mitochondrial Apoptosis by Regulating PUMA Levels
2. Breast cancer cell cooperation can spur tumor growth
- Subpopulations of breast cancer cells sometimes cooperate to aid tumor growth, according to Penn State College of Medicine researchers.
- Cancers contain genetically different subpopulations of cells, called subclones.
- Researchers have long known that these mutant subclones aggressively compete with one another to become the dominant tumor cell population. However, in some cases it seems that no single subclone can achieve dominance on its own.
- No single subclone seems to be capable of gaining the upper hand, leading to the conjecture whether subclones might be working together in some instances.
- Cooperation between subclones could provide a stabilizing force that preserves tumor cell diversity.
- The researchers observed a co-dependency of the two subpopulations. Instead of competing, the two relied on each other to expand both populations.
- When the researchers prevented the signaling between cells, the cancer growth stopped. However, the longer the messaging between the cells stops, the greater the chance that the cells will adapt.
- Research could lead to effective ways to block communication between the cells to prevent the cooperation, and slow cancer growth.
- For more information: Nature 508, 113–117 (03 April 2014) doi:10.1038/nature13187, Tumour cell heterogeneity maintained by cooperating subclones in Wnt-driven mammary cancers
3. Cancer could be ‘starved’ by taking pills that remove copper from the body
- Increase in copper molecules in blood can cause cancer cells to ‘breathe’, causing higher growth rates
- The new study has shown copper levels could play a part in forms of the disease that possess a common mutation in a cancer-causing gene called BRAF.
- BRAF-positive cancers like melanoma almost hunger for copper.
- The BRAF kinase is mutated, typically Val 600Glu (V600E), to induce an active oncogenic state in a large fraction of melanomas, thyroid cancers, hairy cell leukaemias and, to a smaller extent, a wide spectrum of other cancers
- The BRAF gene is involved in regulating cell division and differentiation. When mutated it causes cells to go out of control.
- Scientists found when they blocked copper uptake by tumours with the BRAF mutation they stopped developing.
- This even happened in cells resistant to treatment with compounds targeting the BRAF mutation.
- Dr Donita Brady, who led the study, said: ‘Oral drugs used to lower copper levels in Wilson disease could be repurposed to treat BRAF-driven cancers like melanoma – or perhaps even others like thyroid or lung cancer.’
- Scientist believe that pills to reduce copper could ‘starve’ the cancer cells
For more information, Nature, doi:10.1038/nature13180, Copper is required for oncogenic BRAF signalling and tumorigenesis
4. Elderly people showing signs of dementia are 30% less likely to die from cancer
- Spanish study tested over-65s on their memory skills over 13 years
- Group with fast decline in skills were 30 per cent less likely to die of cancer
- But scientists are still unable to explain why this is so
- The study was supported by the Spanish Health Research Agency, the Spanish Office of Science and Technology, the National Institutes of Health and the European Commission.
For more information: Neurology, https://www.aan.com/PressRoom/Home/PressRelease/1267
5. Two new genes modulating breast and ovarian cancer risk discovered
- A new study has found the two new genes that influence the risk of women developing breast and ovarian cancer.
- Scientists at the Spanish National Cancer Research Centre (CNIO) are currently conducting a study that will contribute towards spreading awareness about the genes when they carry BRCA1 and BRCA2 mutations.
- According to the study the DNA variants may be caused by a single change, SNPs (Single-nucleotide polymorphisms), which do not inactivate genes and nor are they pathological in and of themselves, but they can play an important role when high-risk mutations already exist.
- The researchers have said that these genes could explain why some women with high-risk mutations suffer from cancer while others do not.
For more information: PLOS Genetics (2014). DOI: 10.1371/journal.pgen.1004256, DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.The researchers have said that these genes could explain why some women with high-risk mutations suffer from cancer while others do not.
6. Bacteria may play a role in breast cancer
- “It probably sounded too far-fetched,” said Dr. Gregor Reid, a professor of microbiology and immunology and surgery at Western University and an endowed chair at the Lawson Health Research Institute.
- He expected to find bacteria in and near the nipple, but then came the surprise: In women with breast cancer, there was bacteria near the tumour deep within the breast.
- Reid next plans to find out what role the bacteria play — is their placement coincidental, a result of cancer or a cause of cancer?
For more information: Applied and Environmental Microbiology, doi:10.1128/AEM.00242-14, Bacterial microbiota of human breast tissue
7. Fertility Treatment Not Associated With Increased Risk Of Breast Cancer
- A recent study has shown that women who take clomiphene citrate or gonadotropins are no more likely to develop breast cancer than women who don’t receive fertility treatment.
- It is not clear why previous studies have hinted at an elevated cancer risk for women on fertility treatment. One possible explanation, the team says, is that the observed risk may be related to persistent infertility rather than the prescribed medication.
- Still, more research is needed before any broader claims can be made. that while the current findings are pretty clear, researchers should not take their eyes off the study sample just yet.
- “This cohort of women should continue to be monitored as they progress into a typical breast cancer age range. In addition, data are needed to assess the long-term effects of fertility drugs given in current practice, such as those used in conjunction with IVF.”
For more information: Cancer Epidemiology, Biomarkers & Prevention, doi: 10.1158/1055-9965.EPI-13-0996, Long-term Relationship of Ovulation-Stimulating Drugs to Breast Cancer Risk
8. In mice, obese dads produce heavier daughters with epigenetically altered breast tissue
- Obese male mice and normal weight female mice produce female pups that are overweight at birth and in childhood, and have increased number of “terminal end buds” in their breast tissue—the site where cancer often develops in rodents.
- In addition, the researchers say they’ve found evidence that obesity could change the microRNA (miRNA) signature—epigenetic regulators of gene expression—in both the dad’s sperm and the daughter’s breast tissue, suggesting that miRNAs may carry the epigenetic information from obese dads to their daughters.
- The miRNAs identified are known to regulate insulin receptor signaling, which is linked to alterations in body weight, and others molecular pathways that are associated with breast cancer development such as estrogen receptor signaling.
- The researchers have previously found that pregnant rats that ate a high fat diet increased breast cancer risk in their female daughters and “granddaughters.” That same risk was passed down from the son of the high-fat fed mother to the son’s daughter.
14. Pfizer trial shows palbociclib extends survival time
- Pharmaceutical company Pfizer’s Phase 2 study, involving women with the most common form of breast cancer, found that those treated with hormone drug letrozole, together with its experimental drug palbociclib, lived for an average of 20.2 months before their cancer progressed, compared with 10.2 months for patients given only letrozole.
- However, overall survival has not yet been shown to be statistically significant, researchers said.
- Hormonal agents, like Femara, have extended survival for women with oestrogen-positive, HER2 negative breast cancer, but there have been no big advances in treatment for nearly two decades, said Dr Judy Garber, a breast cancer specialist at Boston’s Dana-Farber Cancer Institute, who was not involved in the palbociclib trial.
- The United States Food and Drug Administration has granted “breakthrough” status for palbociclib.
15. Trial shows neratinib better than Herceptin in HER2 breast cancers
- A mid-stage trial of Puma Biotechnology’s experimental drug neratinib showed that it was more effective, given before surgery, than Herceptin, the Roche drug commonly used in women with a type of breast cancer fueled by a protein called HER2.
- The trial involved treating 193 newly diagnosed patients prior to surgery. About 39 percent of HER2 patients given a combination of neratinib and chemotherapy achieved a “pathologic complete response,” compared with 23 percent of women treated with chemo and Herceptin.
- Pathologic complete response, or pCR, means there is no remaining evidence of the tumor in the breast or lymph nodes.
- The trial also found that the experimental drug resulted in a higher rate of pCR, 45 percent, than standard care, 29 percent, in women with tumors for which genetic testing indicated a high probability that their cancer would return.
- Neratinib, a pill, has a different mechanism of action than Herceptin, a bioengineered antibody given by infusion, as well as Perjeta, a newer Roche drug approved for use in combination with Herceptin.
- As a result, HER2-positive patients could potentially be treated with a regimen of chemotherapy, plus Herceptin, Perjeta and neratinib.
16. New drug LY2835219 show promise for metastatic breast cancer
- Preclinical evaluation indicated that LY2835219 may have a potential therapeutic application for the treatment of human cancers in
- This study was funded by Eli Lilly and Company.
17. Invasive lobular carcinoma may benefit from different treatment approach
- Invasive lobular carcinoma, characterized by a unique growth pattern in breast tissue that fails to form a lump, has distinct genetic markers
- Recent analyses suggest that a subset of patients with lobular carcinoma receive less benefit from adjuvant tamoxifen than patients with ductal carcinoma
For more information: The Journal of Cancer Research, doi: 10.1158/0008-5472.CAN-13-2779, ERRγ Mediates Tamoxifen Resistance in Novel Models of Invasive Lobular BreastCancer