Best of Breast: news for week ending 17 January 2014

A summary of  Google Alerts for Breast Cancer and Cancer for the week ending 17 January 2014.

In previous posts, I’ve bemoaned the fact that scientists have already found cures for cancer, but unfortunately they are only at the premature rat-and-mouse trial stage.

This week, it’s the turn of the naked mole rat to take centre-stage. As you can see, it’s not going to win prizes for its looks, but I don’t care – I wish I were a naked mole rat.

naked-mole-rat0_2328106b

I may be ugly and I lisp, but I’ll never get canther!  (photo of naked mole rat)

Metastasis is the theme this week.

Scientists discover how cancer cells can turn themselves into brain cells to evade capture, and in yet another example of how evil and sneaky they are, transform into brain tumours.  It explains how people in remission can later develop brain tumours.  (Not helpful for the millions of women who already have brain tumours, but may lead to the development of treatments that will prevent such metastasis in other breast cancer patients.)

In the second expose on metastasis, scientists identify two types of cancer stem cells that are necessary for metastasis to happen.  What’s interesting is that current tests that look at tumor cells circulating in the blood to help determine whether the cancer is spreading do not appear to detect one of the variants.  So a CTC (circulating tumour cell) count test may not be enough to work out whether or not a cancer will metastasise.

There’s an interesting study on how multiple sclerosis patients in Taiwan are more prone to developing cancer – the mechanism behind this is.  At the conference in Fulda that I attended last year, Dr Kenny de Meirleir of Vrige Universiteit (Free University)  Brussel, Belgium presented a talk on Myalgic encephalomylitis and CFS and inflammatory processes, in which he showed the link between inflammation and chronic illnesses – more in a later post.

1.  Could mole rats hold the key to a cure for cancer? Scientists hail ‘potentially life-changing’ breakthrough

  • Blind mole rats are one of a unique group of animals that spend their lives underground, are tolerant of very low oxygen levels (down to only 3% concentration – levels that would kill a human), have a long lifespan of more than 20 years, which is exceptional for a small rodent, and show no clear signs of ageing or age-related diseases.
  • Unlike other small rodents, mole rats have never been observed to get cancer. Researchers say that in 50 years of examining thousands of mole rats, they have never observed a single spontaneously growing cancer.
  • This particular piece of research carried out various experiments with the aim of seeing whether:
    • the blind mole rat is resistant to chemically-induced cancer growth
    • fibroblasts (connective tissue cells that play a role in wound healing) from the blind mole rat demonstrate cancer-killing properties
  • This research has demonstrated the unique abilities of the blind mole rat to resist cancer, even when directly given potent cancer-causing chemicals.
  • In the laboratory, the researchers also demonstrated how connective tissue cells called fibroblasts taken from the animal seem to play an important role in this cancer resistance. These cells prevented the growth of human cancer cells when the two types of cells were grown together in the laboratory.

For more information:

Pronounced cancer resistance in a subterranean rodent, the blind mole-rat, Spalaxin vivo and in vitro evidence

Chameleon

Just call me a breast cancer brain cell …

2.  How ‘chameleon-like’ breast cancer cells lead to brain tumors

  • Breast cancer cells are cellular chameleons and masquerade as neurons, allowing them to hide from the immune system, cross the blood-brain barrier and begin to form deadly brain tumors.
  • Taking samples from brain tumors which metastasised from breast cancer, researchers found that the breast cancer cells were using the brain’s most abundant chemical as a fuel source.
  • This chemical, GABA, is a neurotransmitter used for communication between neurons.
  • When compared to cells from non-metastatic breast cancer, the metastasized cells expressed a receptor for GABA, as well as for a protein that draws the transmitter into cells. This allowed the cancer cells to essentially masquerade as neurons.
  • The study also found that the cells have the ability to modify their genetic machinery and produce clones with additional survival skills. This means that as the cells increase in number, they also increase in strength.
  • The study was led by Rahul Jandial, M.D., Ph.D., a City of Hope neuro-surgeon, and is available online and scheduled for print publication in the Proceedings of the National Academy of Science in February.
  • “There remains a paucity of public awareness about cancer’s relentless endgame,” said Dr. Jandial, the doctor who led the study. “Cancer kills by spreading. In fact, 90 percent of all cancer mortality is from metastasis … The most dreaded location for cancer to spread is the brain. As we have become better at keeping cancer at bay with drugs such as Herceptin, women are fortunately living longer. In this hard-fought life extension, brain metastases are being unmasked as the next battleground for extending the lives of women with breast cancer,” he said.

For more information:  City of Hope’s blog

3.  New Breast Cancer Stem Cell Findings Explain How Cancer Spreads – Researchers identify two types of cancer stem cells (both necessary to create metastasis)

  •  Breast cancer stem cells exist in two different states and each state plays a role in how cancer spreads, according to an international collaboration of researchers.
  • This finding sheds new light on the process that makes cancer a deadly disease.
  • Cancer stem cells are responsible for metastasis – they are the seeds that mediate cancer’s spread. Now it has been discovered how they do this.
  • First, on the outside of the tumor, a type of stem cell exists in a state called the epithelial-mesenchymal transition (EMT) state.
  • These stem cells appear dormant but are very invasive and able to get into the bloodstream, where they travel to distant parts of the body.
  • Once there, the stem cells transition to a second state that displays the opposite characteristics, called the mesenchymal-epithelial transition state (MET). These cells are capable of growing and making copies of themselves, producing new tumors.
  • Both forms of cancer stem cells are needed to metastasize and grow in distant organs.
  • If the stem cell is locked in one or the other state, it can’t form a metastasis.
  • Researchers must now understand whether new therapies must attack both forms of the stem cell to be successful.
  • Different pathways regulate each type of stem cell, which suggests that effective therapies must be able to target multiple pathways.
  • In addition, current tests that look at tumor cells circulating in the blood to help determine whether the cancer is spreading do not appear to capture the EMT stem cells, which are the cancer cells that travel through the blood.
  • U-M researchers are working with colleagues from the U-M College of Engineering to develop new tools to isolate the EMT stem cells from the blood of cancer patients.

For more information:

Reference: Stem Cell Reports, Vol. 2, No. 1; Jan. 14, 2014

4.  Patients with multiple sclerosis in Taiwan may be at increased risk of developing cancer

  • Individuals with multiple sclerosis may have an increased risk of developing any type of cancer, with an especially high risk of developing breast cancer.
  • That is the conclusion of a recent study published in European Journal of Neurology.
  • Because the findings contradict earlier studies, additional research is needed to determine whether a true link exists between multiple sclerosis and cancer.
  • Our study was a nationwide population-based cohort study, and it revealed unexpected findings,” said Dr. Sun.
  • Specifically, the team found that individuals with multiple sclerosis were 85% more likely to develop cancer than the controls.
  • Their risk of developing breast cancer was especially high, with more than a 2-fold increased risk over controls.
  • The findings suggest that patients with multiple sclerosis patients may need to be monitored closely to ensure early detection of cancer.
  • Dr. Sun notes that it is unclear why his team’s results are not consistent with most other studies.
  • “The underlying genetic and environmental factors in Taiwan, which differ from those of western countries, might play an undetermined role. Additional large-scale studies will help improve our understanding,” he said.

For more information: “Increased breast cancer risk for patients with multiple sclerosis: a nationwide population-based cohort study.” L.-M. Sun, C.-L. Lin, C.-J. Chung, J.-A. Liang, F.-C. Sung, and C.-H. Kao. European Journal of Neurology; Published Online: January 14, 2013 DOI: 10.1111/ene.12267

5.  Sequential chemo best in metastatic breast cancer

  • Combination chemotherapy does not provide a survival benefit to women with metastatic breast cancer compared with sequential therapy, an Australian-authored Cochrane review finds.
  • In fact, combination therapy carried a 16% higher risk of disease progression – a result that remained consistent across a number of subgroups, according to the analysis of 12 trials and over 2,300 patients.
  • However, overall survival was about the same in both therapies, the authors from the University of Sydney and Westmead Hospital found.
  • Risk of febrile neutropia was 32% higher with combination therapy…

6.  Nanoparticles catch cancer in pincer movement

  • Researchers have developed a technique for creating nanoparticles that carry two different cancer-killing drugs into the body and deliver them to separate parts of the cancer cell.
  • The technique was developed by researchers at North Carolina State University and the University of North Carolina at Chapel Hill.
  • Cancer cells can develop resistance to chemotherapy drugs, but are less likely to develop resistance when multiple drugs are delivered simultaneously.
  • However, different drugs target different parts of the cancer cell.
  • For example, the protein drug TRAIL is most effective against the cell membrane, while doxorubicin (Dox) is most effective when delivered to the nucleus.
  • The research team came up with a sequential and site-specific delivery technique that first delivers TRAIL to cancer cell membranes and then penetrates the membrane to deliver Dox to the nucleus.
  • They developed nanoparticles with an outer shell made of hyaluronic acid (HA) woven together with TRAIL. The HA is said to interact with receptors on cancer cell membranes, which ‘grab’ the nanoparticle. Enzymes in the cancer cell environment break down the HA, releasing TRAIL onto the cell membrane and ultimately triggering cell death.
  • When the HA shell breaks down, it also reveals the core of the nanoparticle, which is made of Dox that is embedded with peptides that allow the core to penetrate into the cancer cell. The cancer cell encases the core in a protective bubble – an endosome – but the peptides on the core cause the endosome to begin breaking apart. This spills the Dox into the cell where it can penetrate the nucleus and trigger cell death.

The paper, ‘Gel–Liposome-Mediated Co-Delivery of Anticancer Membrane-Associated Proteins and Small-Molecule Drugs for Enhanced Therapeutic Efficacy,’ is published online in Advanced Functional Materials.

7.  Trastuzumab benefit predicted by high levels of immune cells in breast cancer tumors

  • Women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who had the highest levels of immune cells in their tumors gained the most benefit from presurgery treatment with chemotherapy and trastuzumab.
  • These results were presented at the 2013 San Antonio Breast Cancer Symposium, December 10-14, 2013 by Sherene Loi, MD, PhD, medical oncologist and head of the Translational Breast Cancer Genomics Lab at the Peter MacCallum Cancer Centre in Melbourne, Australia.
  • “These data indicate that a patient’s immune system influences outcome and trastuzumab response,” said Loi. “What we don’t know is why some patients have tumor-infiltrating lymphocytes in their breast tumor at diagnosis and others do not. Currently, we are actively investigating this and trying to understand why there is a positive relationship between tumor-infiltrating lymphocytes and better outcomes with trastuzumab therapy.”
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