The weekly summary of news from Google Alerts for Breast Cancer and Cancer, for week ending 18 July 2014.
This week opens with a vaccine for cancer made from a manipulated version of toxoplasmosis gondii, a parasite which is often passed through cat poo, or eating contaminated meat. About a third of the US population has toxoplasmosis. In a healthy person, the infection causes mild symptoms. However, in an immune-compromised person (e.g. with HIV/AIDS or undergoing chemotherapy), toxoplasmosis can give rise to serious side-effects such as encephalitis (inflammation of the brain) and death.
It’s something that not a lot of oncologists or surgeons know about. Often, swollen lymph nodes, which is one of the symptoms of toxoplasmosis can be mistaken for lymphoma. There have been cases of biopsies of lymph nodes in breast cancer showing signs of toxoplasmosis. Which came first? Did the toxoplasmosis cause the breast cancer? Or did the cancer suppress the immune system to activate the toxoplamosis?
Toxoplasmosis, once acquired, cannot be got rid of. The infection becomes latent, only to be re-activated when the person’s immune system is suppressed.
So it’s interesting that scientists have taken something that can be potentially deadly and manipulated it and turned it into a vaccine.
The second article is not new – that using morphine-based pain-relief can cause metastasis. Something to bear in mind if you’re thinking of having surgery.
1. Cure for cancer? Cat poop parasite remedy
- A mutated strain of a cat poop parasite has been found to reprogramme the natural power of the immune system to kill cancer cells, scientists say.
- Toxoplasma gondii (T gondii) is a single-celled parasite found in a cat’s intestines, but it can live in any warm blooded animal.
- T gondii affects about one-third of the world’s population. Most people have no symptoms, but some experience a flu-like illness. Those with suppressed immune systems, however, can develop a serious infection if they are unable to fend off T gondii.
- A healthy immune system responds vigorously to T gondii in a manner that parallels how the immune system attacks a tumour.
- In response to T gondii, the body produces natural killer cells and cytotoxic T cells. These cell types wage war against cancer cells. Cancer can shut down the body’s defensive mechanisms, but introducing T gondii into a tumour environment can jump start the immune system.
- Since it isn’t safe to inject a cancer patient with live replicating strains of T gondii, Bzik and Fox created “cps,” an immunotherapeutic vaccine.
- Based on the parasite’s biochemical pathways, researchers delete a Toxoplasma gene needed to make a building block of its genome and create a mutant parasite that can be grown in the laboratory but is unable to reproduce in animals or people.
- Even when the host is immune deficient, cps still retains that unique biology that stimulates the ideal vaccine responses.
- “Aggressive cancers too often seem like fast moving train wrecks. Cps is the microscopic, but super strong, hero that catches the wayward trains, halts their progression, and shrinks them until they disappear.”
- Published laboratory studies from the Geisel School of Medicine labs have tested the cps vaccine in extremely aggressive lethal mouse models of melanoma or ovarian cancer and found unprecedented high rates of cancer survival.
For more information: http://geiselmed.dartmouth.edu/faculty/facultydb/view.php?uid=129
2. Type of anaesthesia used during breast cancer surgery may affect the risk of cancer recurrence
- New research findings indicate that the type of anaesthetic used during surgery could affect the metastatic potential of cancer cells.
- Scientists took blood before and after surgery from breast cancer patients who had been given different types of anaesthetic and pain relief.
- Some of the women had used standard inhaled general anaesthetics with morphine based pain relief
- Others had been anaesthetised using regional (breast numbing) techniques with a single intravenous general anaesthetic called propofol to minimize morphine dosing.
- In laboratory conditions, breast cancer cells were then exposed to these blood samples.
- The scientists found that the blood from patients who had been given standard inhaled general anaesthetics with morphine pain relief reduced a process known as “apoptosis” whereby the body’s cells naturally die off.
- In contrast, cancer cells exposed to blood from patients who had been given regional anaesthesia and propofol showed a higher rate of apoptosis, or natural death of cancer cells.
- In separate research also carried out at University College Dublin and published in this Special Issue of the British Journal of Anaesthesia on Cancer and Anaesthesia, laboratory tests indicate that anaesthetic technique can affect the activity of the body’s immune system and its Natural Killer (NK) cells.
- NK cells are important in the body’s resistance to the spread of cancer. Blood from breast cancer patients was exposed to NK cells and breast cancer cells.
- The blood from patients who had been given regional anaesthesia and propofol resulted in more Natural Killer cell anti-cancer activity than the blood from patients who received standard inhaled general anaesthetics with morphine pain relief.
- For more information: British Journal of Anaesthesia, (2014) doi: 10.1093/ bja/ aet581 Differential effects of serum from patients administered distinct anaesthetic techniques on apoptosis in breast cancer cells in vitro: a pilot study
3. Tamoxifen gel has fewer side-effects
- Tamoxifen, which is also available as a sugar free liquid called Saltamox, often comes with hormonal side effects and blood clotting.
- Now a study by Northwestern University in Chicago has now shown that using it in gel form is as effective in treating the cancer, while limiting these side effects.
- Because the drug was absorbed through the skin directly into breast tissue, blood levels of the drug were much lower, thus, potentially minimizing dangerous side effects — blood clots and uterine cancer.
- The gel was tested on women diagnosed with the non-invasive cancer ductal carcinoma in situ (DCIS) in which abnormal cells multiply and form a growth in a milk duct. Because of potential side effects, many women with DCIS are reluctant to take oral tamoxifen after being treated with breast-saving surgery and radiation even though the drug effectively prevents DCIS recurrence and reduces risk of future new breast cancer.
- “The study showed women who applied the gel had similar levels of tamoxifen in the breast tissue to those taking the pill version, which is the normal form in which the drug is taken, and lower levels of the drug in their blood – which could lead to fewer side effects.”
- “Although these findings are very interesting, the research was conducted over a short time period on a small group of women who already had an early form of breast cancer.
- “Results have not yet proved that tamoxifen gel can prevent breast cancer or that there will be fewer side effects compared to the pill form.”
For more information: http://www.northwestern.edu/newscenter/stories/2014/07/new-skin-gel-fights-breast-cancer-without-blood-clot-risk.html#sthash.ObjuH4NT.dpuf and also: Clinical Cancer Research, July 15, 2014 20; 3672, doi: 10.1158/1078-0432.CCR-13-3045, A Randomized Phase II Presurgical Trial of Transdermal 4-Hydroxytamoxifen Gel versus Oral Tamoxifen in Women with Ductal Carcinoma In Situ of the Breast
4. Metastasis – chance or genetics?
The conventional view of metastasis, has been that only “specialist” cells from the primary tumour can cause the growth of new tumours elsewhere in the body.
- The cells have the ability to perform a number of different tasks, such as invading local tissue, entering, surviving in and leaving the bloodstream, and colonising new tissue environments.
- The view explains the inefficiency of metastasis and why it often takes years to cause death in most patients, as it is highly improbable that a cell will possess all of the genetic mutations required to carry out all of the functions.
- However, using statistical models and theories on probability, the researchers found large numbers of common cancer cells that flow freely in the blood stream can also cause metastasis by pure chance.
- “If we use a military metaphor, a key mission can be accomplished using either a handful of highly trained special forces – in this case the specialist cells – or a huge number of untrained infantry – the common cancer cells – in which case a handful of ordinary soldiers will, by sheer luck, be successful. If one could magically observe the early growth of a metastasis, we show there would be no way of telling from the growth dynamics whether the tumour was seeded by a special forces cell or a lucky infantryman.”
- The study, which has been published in the Physical Biology journal, concludes that successful metastatic growth from common cells, although rare, would proceed extremely rapidly.
- It could spur new ways of thinking about cancer research, demonstrating that statistical physics may be as fundamental as complex genetics when studying the occurrence and treatment of the disease.
- “If we allow ourselves to consider the role of randomness, then we open the door to perceiving surprising effects of the statistical fluctuations that may not be expected by naive reasoning.”
For more information: IOP Science Physical Biology, 11 046003
doi:10.1088/1478-3975/11/4/046003, Quantifying metastatic inefficiency: rare genotypes versus rare dynamics
5. Enzyme and gene deficiency discoveries as potential new anti-cancer agents
- The journal Cancer Cell today published research led by Dr. Tak Mak mapping the path of discovery to developing a potential anticancer agent.
- “What began with the question ‘what makes a particular aggressive form of breast cancer cells keep growing?’ turned into 10 years of systematic research to identify the enzyme PLK4 as a promising therapeutic target and develop a small molecule inhibitor to block it.”
- In the lab, the scientific team used an approach that combined functional RNAi analysis with gene expression analysis in breast cancer-derived cell lines and in human breast cancers replicated in mice. Using these multidimensional datasets for human breast cancer, PLK4 was identified as a candidate target among 10,000 other targets for the development of anticancer therapeutics.
- “The research showed that the aggressive form of basal breast cancer cells may be dependent on PLK4 for survival and that depleting it induced cell death,” says Dr. Mak. “This finding led to the identification of CFI-400945, a selective and orally active inhibitor of PLK4, which was shown to have significant antitumor activity as a single agent in a variety of preclinical tumor models.”
- Another key finding was observing the inhibitor effect on tumor models with a gene PTEN deficiency as a biomarker – of huge interest because PTEN, a tumor suppressor, is known to be defective in as many as half of all advanced solid tumor cancers.
For more information: Cancer Cell, DOI: http://dx.doi.org/10.1016/j.ccr.2014.05.006, Functional Characterization of CFI-400945, a Polo-like Kinase 4 Inhibitor, as a Potential Anticancer Agent