Best of Breast: news for week ending 11 April 2014

A summary of news for the week ending 11 April 2014 from Google Alerts – Breast Cancer and Cancer. ZombieAttack 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!

ZombieChart

Cancer cells at work. Image credit: thinkgeek.com

1.  Zombie cancer cells eat themselves to live

http://medicalxpress.com/news/2014-04-zombie-cancer-cells.html

  • 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.
GRAPHICAL ABSTRACTv2 copy

How to become a Zombie Cancer Cell …

For more information:  Cell ReportsVol. 7Issue 1p45–52, DOI: http://dx.doi.org/10.1016/j.celrep.2014.02.036Autophagy 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
Copper-pipes

Copper … the villain within? image credit: vtdigger.org

3.  Cancer could be ‘starved’ by taking pills that remove copper from the body

http://www.dailymail.co.uk/news/article-2601187/Cancer-starved-taking-pills-remove-copper-body-say-scientists.html

  • 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 600right arrowGlu (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

http://www.dailymail.co.uk/health/article-2601528/Dementia-cut-risk-cancer.html?ITO=1490&ns_mchannel=rss&ns_campaign=1490

  • 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

http://www.torontosun.com/2014/04/08/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

http://www.medicaldaily.com/fertility-treatment-not-associated-increased-risk-breast-cancer-274264

  • 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

OverweightMice

image credit: upi.com

8.  In mice, obese dads produce heavier daughters with epigenetically altered breast tissue

http://medicalxpress.com/news/2014-04-mice-obese-dads-heavier-daughters.html

  • 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 , 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.
 The findings, presented by a Georgetown Lombardi Comprehensive Cancer Center researcher at the AACR Annual Meeting 2014, come from one of the first animal studies to examine the impact of paternal obesity on future generations’ cancer risk.
See also this article:  Fat fathers ‘more likely to produce sons and daughters who struggle with their weight’
  • Scientists saw a trend in mice whose fathers had grown obese
  • Mice put on weight from six weeks despite being fed a healthy low-fat diet
  • Researchers are investigating the biological processes involved and the connection with humans

9.  Father’s age at birth may affect daughter’s cancer risk

http://www.business-standard.com/article/pti-stories/father-s-age-at-birth-may-affect-daughter-s-cancer-risk-114040900605_1.html

  • Women born to a father under the age of 20 had a 35 per cent greater risk of breast cancer and more than two times greater risk of ovarian cancer, when compared to those born to a father whose age at his daughter’s birth was 25 to 29 years old.
  • Women born to a father whose age at childbirth was 30 to 34 years had a 25 per cent greater risk of endometrial cancer than those born to a father age 25 to 29.
  • Researchers were not surprised to find a relationship between older fathers and an increased risk of hormone-related cancers, especially since there has been increasing evidence suggesting that daughters born to older fathers have increased risk of breast cancer.
  • However, there have been no previous studies that examine the effects that young paternal age has on a daughter’s breast cancer risk or the effects of parental age on the risk of ovarian cancer and endometrial cancer.
  • “We observed that young paternal age, as well as advanced paternal age, increase the risk of breast cancer. We also found that young paternal age increases the risk of ovarian cancer,” said a researcher from City of Hope in the US.
  • The findings were presented at the American Association for Cancer Research’s annual meeting in San Diego.
MagneticNanoparticles

Magnetic nanoparticle (mNP) hyperthermia: Shown here at 9900x magnification, tumor cells readily take up magnetic nanoparticles (black objects). When a tumor containing nanoparticles is exposed to an alternating magnetic field, the nanoparticles will heat and kill the tumor cells. Image credit: news-medical.net

10.  Magnetic nanoparticle (mNP) hyperthermia in breast cancer treatment

http://www.news-medical.net/news/20140408/Magnetic-nanoparticle-(mNP)-hyperthermia-in-breast-cancer-treatment.aspx

  • This evolving treatment approach involves the injection of nanoparticles into the tumor, which are then activated with magnetic energy.
  • Once activated the nanoparticles produce heat inside the cancer cell. The heat kills the cancer cell with minimal damage to surrounding tissue.
zombie zapper

Just add cancer cells …

For more information:  Norris Cotton Cancer Center’s Nanotechnology Working Group and the Dartmouth Center of Nanotechnology Excellencethe Dartmouth Center of Nanotechnology Excellence.  Presented at the annual meeting of the American Association for Cancer Research (AACR)

11.  Tissue testing during breast cancer lumpectomies helps minimise repeat surgery

http://www.sciencecodex.com/tissue_testing_during_breast_cancer_lumpectomies-131266

  • Unique laboratory testing during breast cancer lumpectomies to make sure surgeons remove all cancerous tissue spares patients the need for a repeat lumpectomy in roughly 96 percent of cases at Mayo Clinic in Rochester, a success rate much higher than the rate nationally, a Mayo study shows.
  • During the years reviewed, 13.2 percent of breast cancer lumpectomy patients nationally had to return to the operating room within a month of their initial surgery, compared to 3.6 percent at Mayo in Rochester, which uses a technique called frozen section analysis to test excised tissue for cancer while patient are still on the operating table.

12.  New drug, AMPI-109, and molecular insight into triple negative breast cancers

  • Research shows thata new drug, AMIP-109, was especially effective in specifically one subtype: triple-negative breast cancer, in which the drug blocked the growth of cells by greater than 50 percent.
  • AMPI-109 binds to the catalytic site of the PTP4A3 protein and impairs its ability to function, offering the first evidence that this newly discovered triple-negative breast cancer oncogene may be targetable with AMPI-109.
  • Not only did data identify PTP4A3 as a potential oncogene in triple negative breast cancer, but it also offers the first reported evidence that AMPI-109 prevents the growth and migratory capability of triple negative breast cancers by targeting PTP4A3.
  • We may be able to use PTP4A3 protein levels as a predictive marker to determine which patients may best respond to treatment with AMPI-109
  • “If PTP4A3 is an oncogenic driver of triple negative breast cancer, and if our inhibits it by this mechanism, this could have strong clinical importance for the population of the people with this disease, for whom treatment has been especially challenging.”

For more information:  http://www.ucdenver.edu/academics/colleges/medicalschool/departments/Pathology/research/Pages/lambertlab.aspx and American Association for Cancer Research (AACR) Annual Meeting 2014

13.  Dosage and schedules may improve effects of PI3K-inhibitors to target breast cancer tumors

  • Research suggests that manipulation of drug dosage and schedules may improve anti-tumor effects of PI3K-inhibitors to target breast cancer tumors.
  • Researchers noted that in clinical studies, novel drugs are often delivered in escalating doses until toxicities are observed in patients; this approach doesn’t provide information on target inhibition in tumors. Current PI3K inhibitor treatment regimens incompletely and temporarily inhibit the pathway in cancers, and are often accompanied by adverse effects in patients.
  • These findings have implications for the optimal strategy to use such drugs in patients, and lay the groundwork for future development of anti-cancer therapeutics.
  • Sixty-five percent of all breast cancers are estrogen receptor positive (ER+), with tumors that can stop growing or die when treated with drugs that block estrogen signaling.
  • Eighty percent of these ER+ breast cancers have mutations on the PI3K pathway, which regulates cell growth.
  • Drugs that target the PI3K pathway have shown promise for the treatment of anti-estrogen-resistant breast cancers in early clinical trials.

For more information: http://cancer.dartmouth.edu/about_us/newsdetail/66201/ “Pharmacodynamic analysis of PI3K inhibition in breast tumors: a model to improve early clinical investigation of novel agents,” will be in Hall A-E Section 33 from 8:00-12:00 pm PT on April 8, 2014 at the AACR Conference.

 14.  Pfizer trial shows palbociclib extends survival time

http://www.health24.com/Medical/Breast/News/Pfizer-drug-increases-breast-cancer-survival-time-20140406

  • 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

http://uk.reuters.com/article/2014/04/07/us-cancer-puma-idUKBREA3612G20140407

  •  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

http://www.sciencecodex.com/common_breast_cancer_subtype_may_benefit_from_personalized_treatment_approach-131172 I

  • 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

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2 responses

  1. More on Copper :
    1. Copper deficiency as an anti-cancer strategy (intl-erc.endocrinology-journals.org/content/11/2/255.full.pdf)
    2. Copper-lowering drug stabilizes advanced cancer in anti-angiogenesis trial (www.cancer.med.umich.edu/news/relcopper.htm)
    3. Treatment of Metastatic Cancer with Tetrathiomolybdate, an Anticopper, Antiangiogenic Agent: Phase I Study1 (https://clincancerres.aacrjournals.org/content/6/1/1.full)

    j

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