New developments in Breast Cancer and Cancer from Google Alerts for the week ending 4 July 2014.
The first article steps straight into the controversy about the use of antioxidants in cancer patients. Some doctors/scientists believe that they actually protect the cancer cells; however, another school believes that antioxidants can protect healthy cells from free radicals and prevent further cancer formation.
What I found interesting was that finally there was a plausible explanation for why taking antioxidant pills or eating vast quantities of foods rich in antioxidants may be failing to show a beneficial effect against cancer.
It has to do with the fact that cancer cells generate reactive oxygen species (ROS) – aka free radicals – in order to grow and antioxidants “do not act at the critical site in cells where tumor-promoting ROS are produced – at cellular energy factories called mitochondria.”
Rather, supplements and dietary antioxidants tend to accumulate at scattered distant sites in the cell, “leaving tumor-promoting ROS relatively unperturbed.”
So the dilemma still remains for those cancer patients who pop pills: antioxidant supplements or no?
Update: thank you to reader JT who pointed out this study which showed that antioxidant supplementation during chemotherapy is beneficial: Cancer Treatment Reviews, 2007 Aug;33(5):407-18, Impact of antioxidant supplementation on chemotherapeutic efficacy: a systematic review of the evidence from randomized controlled trials [full paper]. One of the authors of the study is Dr Keith Block of the Institute for Integrative Cancer Research and Education, Illinois, USA, which lends the study clinical authority. See also this fantastic study sent by JT: http://virtualtrials.com/pdf/williamssupplements2014.pdf – The Role of Supplements (including Anti-Oxidants) in Cancer Treatment.
1. How antioxidants can accelerate cancers, and why they don’t protect against them
- In a brief paper appearing today in The New England Journal of Medicine, David Tuveson, M.D. Ph.D., Cold Spring Harbor Laboratory Professor and Director of Research for the Lustgarten Foundation, and Navdeep S. Chandel, Ph.D., of the Feinberg School of Medicine at Northwestern University, propose why antioxidant supplements might not be working to reduce cancer development, and why they may actually do more harm than good.
- Their insights are based on recent advances in the understanding of the system in our cells that establishes a natural balance between oxidizing and anti-oxidizing compounds.
- These compounds are involved in so-called redox (reduction and oxidation) reactions essential to cellular chemistry.
- Oxidants like hydrogen peroxide are essential in small quantities and are manufactured within cells.
- There is no dispute that oxidants are toxic in large amounts, and cells naturally generate their own anti-oxidants to neutralize them.
- It has seemed logical to many, therefore, to boost intake of antioxidants to counter the effects of hydrogen peroxide and other similarly toxic “reactive oxygen species,” or ROS [free radicals], as they are called by scientists.
- All the more because it is known that cancer cells generate higher levels of ROS to help feed their abnormal growth.
- Drs. Tuveson and Chandel propose that taking antioxidant pills or eating vast quantities of foods rich in antioxidants may be failing to show a beneficial effect against cancer because they do not act at the critical site in cells where tumor-promoting ROS are produced – at cellular energy factories called mitochondria.
- Rather, supplements and dietary antioxidants tend to accumulate at scattered distant sites in the cell, “leaving tumor-promoting ROS relatively unperturbed,” the researchers say.
- Quantities of both ROS and natural antioxidants are higher in cancer cells – the paradoxically higher levels of antioxidants being a natural defense by cancer cells to keep their higher levels of oxidants in check, so growth can continue.
- In fact, say Tuveson and Chandel, therapies that raise the levels of oxidants in cells may be beneficial, whereas those that act as antioxidants may further stimulate the cancer cells.
- Interestingly, radiation therapy kills cancer cells by dramatically raising levels of oxidants. The same is true of chemotherapeutic drugs – they kill tumor cells via oxidation.
- Paradoxically, then, the authors suggest that “genetic or pharmacologic inhibition of antioxidant proteins” – a concept tested successfully in rodent models of lung and pancreatic cancers—may be a useful therapeutic approach in humans.
- The key challenge, they say, is to identify antioxidant proteins and pathways in cells that are used only by cancer cells and not by healthy cells.
- Impeding antioxidant production in healthy cells will upset the delicate redox balance upon which normal cellular function depends.
- The authors propose new research to profile antioxidant pathways in tumor and adjacent normal cells, to identify possible therapeutic targets.
For more information: The New England Journal of Medicine, 2014; 371:177-178 July 10, 2014 DOI: 10.1056/NEJMcibr1405701, The Promise and Perils of Antioxidants for Cancer Patients [requires subscription]
2. Confirmed: chemical found in coffee, chips and crisps is a cancer risk
- European Food Safety Authority say children are most exposed to acrylamide, which forms when food is roasted, fried or browned
- Organisation has suggested legal controls on the food industry
- Would try and reduce the levels found in products sold to the public
- Food manufacturers in Britain have been under pressure to change their cooking methods and recipes in order to reduce the levels of acrylamide formed during cooking.
- Despite this, the chemical remains at high levels in some products, while acrylamide is also created in the home during roasting and frying.
- A study published by Britain’s Food Standards Agency (FSA) last year found raised levels of the cancer risk chemical have been found in big brand foods from fries sold by KFC to crisps, ginger biscuits and even healthy breakfast cereals.
3. Tuberculosis protein helps spot breast cancer’s signals
- A team at The Institute of Cancer Research, London, used the M. tuberculosis protein to help untangle the complex communication network between breast cancer cells and their healthy neighbours – and begin to describe breast cancer’s communication signature.
- But the new method, described in the journal Molecular and Cellular Proteomics, was able to separate out signals from breast cancer cells from those of a type of healthy cell called fibroblasts, and could be applied to a wide range of different cancers.
- Researchers took advantage of a quirk in the natural production of lysine, one of the 22 amino acid building blocks that make up all the proteins in the human body.
- Scientists grew both healthy and breast cancer cell types in a medium containing ‘heavy’ D-lysine so proteins making use of this precursor could be told apart from those using the other – separating out signals produced by healthy cells and those produced by breast cancer.
- The heavier lysine could be distinguished from lighter lysine using a technique called mass spectrometry.
For more information: Molecular and Cellular Proteomics, mcp.O113.037119, Cell-specific labeling enzymes for analysis of cell-cell communication in continuous co-culture
3. Testosterone fights metastatic breast cancer
- A new trial by doctors in Hospital Santa Maria Nuova-IRCCS in Reggio Emilia, Italy suggests that testosterone can be used as a therapeutic agent to treat hormone-responsive breast cancer, particularly in those whose previous hormone therapies have no longer had any effect against the disease.
- The study shows that 58.5% patients with metastatic breast cancer whose diseases were initially responsive to hormone therapies, but had become resistant and the diseases were progressing, were responsive to the treatment with testosterone propionate.
- As a result of the testosterone therapy, 17.5% patients were in regression and 41.5% had the disease stabilized although progression was observed in the remaining 41.5% patients. The median overall survival was 12 months from the start of testosterone therapy.
- The 53 patients participating in the trial suffered metastatic breast cancer whose prior hormone therapies no longer worked to stop the disease from progressing. In the study, testosterone propionate in a dose of 250 mg once every two weeks, twice, and then once every four weeks until the breast cancer progressed, drug toxicity appeared or death occurred.
- In terms of side effects, hirsutism and dysphonia were observed occasionally, but not severe enough to mandate withdrawal of treatment. No major toxicity was observed except that two patients developed non-fatal pulmonary emboli.
- In the past, testosterone was the most commonly used hormonal therapy to treat this disease, but for whatever reason, its use has been almost completely abandoned in the past 40 years, according to a study report.
- “Testosterone showed a significant therapeutic activity in previously hormone-treated patients with metastatic breast cancer who were no longer responding to such treatment and whose disease was progressing. These results warrant consideration of testosterone use as treatment for patients with hormone-sensitive metastatic breast cancer,” the study concluded.
For more information: Anticancer Res. 2014 Mar;34(3):1287-90, Therapeutic activity of testoterone in metastatic breast cancer.
4. Non-invasive breast cancer detector being developed
- A firm developing an on-the-spot breast cancer and bone disease test has won £50,000 from the Royal Academy of Engineering.
- It said the technique, designed by Oxfordshire’s Cobalt Light Systems, was the most promising technology to come out of the UK this year.
- The test works by analysing the chemical composition of a substance behind virtually any barrier, including skin.
For more information: http://www.cobaltlight.com/news/2014/cobalt-light-systems-wins-macrobert-award-royal-academy-engineering
5. Bra Monitors Body Heat For Breast Cancer Detection
- First Warning Systems has created the FWS Circadian Biometric Recorder (CBRTM), a cancer-detecting bra that enables women to identify malignant tumors in their earliest stages.
- It uses sensors to detect unusual heat patterns in breast tissue in order to identify abnormalities before they become a big problem.
- The CBRTM is applied via a bra insert and records thermodynamic metabolic data, gathering changes in cell activity over a 2 to 12 hour period, after which the results are wirelessly transmitted to a computer for analysis.
- Early research has shown that there’s a 74% correlation to the actual state of cancer in all types of breast tissue, which aids the accurate recording of abnormal dynamic tissue processes which are indicative of the presence of cancer.
- This may not be the end to invasive screenings, as they are more accurate, but the bra has been successfully tested by over 500 patients so far.
- What it does do is mark yet another important and promising advancement in fashion tech that’s geared towards providing personal healthcare alternatives.
For more information: http://www.firstwarningsystems.com/
6. UK: Eribulin for Metastatic Breast Cancer Now Licenced After One Prior Chemotherapy
- From today, Halaven(R) (eribulin) is licenced in the UK for the treatment of patients with locally advanced or metastatic breast cancer (MBC) who have progressed after at least one chemotherapeutic regimen for advanced disease.
- Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting, unless patients were not suitable for these treatments.
- Eribulin is a non-taxane, microtubule dynamics inhibitor currently indicated for the treatment of people with breast cancer who have previously received at least two chemotherapeutic regimens for metastatic disease and whose prior therapy should have included an anthracycline and a taxane.
- Eribulin belongs to a class of antineoplastic agents, the halichondrins, which are natural products, isolated from the marine sponge Halichondria okadai.
- It is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division.
- Study 301, a head-to-head trial of eribulin vs capecitabine [Xeloda] of 1,102 women, had a co-primary endpoint of overall survival and progression-free survival.
- The study demonstrated a trend favouring improved overall survival with eribulin compared to capecitabine in the intention-to-treat population, although the improvement was not statistically significant.
- Women treated with eribulin had a median overall survival of 15.9 months versus 14.5 months with capecitabine (HR 0.879; 95% CI: 0.770-1.003; p=0.056). For women with human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer, overall survival was 15.9 months for eribulin vs 13.5 months for capecitabine (HR 0.838; 95% CI: 0.715-0.983).
- The most common adverse events reported for eribulin and capecitabine (greater than or equal to20% all grades) were neutropenia (54% vs 16%), hand-foot syndrome (<1% vs 45%) alopecia (35% vs 4%), leukopenia (31% vs 10%), diarrhoea (14 vs 29%) and nausea (22% vs 24%), respectively.
7. No strong link between fertility drugs and breast, ovarian and uterine cancers
- There is “little evidence” that the use of conventional fertility hormones used for ovarian stimulation in the treatment of infertility increases the long-term risk of breast and gynecological cancers, according to the results of a substantial 30-year follow-up study.
- However, the extended use of clomiphene citrate was associated with a higher risk of breast cancer among women who had used the fertility drug for 12 cycles or more.
- Gonadotrophins, more commonly used for ovarian stimulation today, were not generally associated with any increased risk, except in a sub-group of women who remained childless after treatment.
- The study was a retrospective investigation involving 12,193 women treated for infertility between 1965 and 1988 at five US sites.
- Follow-up lasted until 2010, with evaluation based on questionnaire and linkage to US death and cancer registries. A total of 9,892 women were successfully followed for cancer outcomes.
For more information: Annual Meeting of ESHRE by Dr Humberto Scoccia from the University of Illinois at Chicago, USA. Dr Louise Brinton of the US National Cancer Institute was principal investigator.(1)
8. Leukemia gene implicated in triple-negative breast cancer
- A team at the University of Glasgow investigated the role of the RUNX1 gene, which is one of the most commonly altered genes in leukaemia.
- However, they have now shown it is also active in the most deadly of triple negative breast cancers.
- Tests on 483 triple negative breast cancers showed patients testing positive for RUNX1 were four times more likely to die as a result of the cancer than those without it.
- However, the gene has a complex role. Normally it is vital for cell survival and plays a critical role in producing blood. However, depending on circumstances, it can either encourage or suppress tumours.
- It means any use of a drug to target the gene might cause side-effects.
For more information: Plos One, DOI: 10.1371/journal.pone.0100759, Expression of RUNX1 Correlates with Poor Patient Prognosis in Triple Negative Breast Cancer
9. Triple-negative patients may benefit from anti-inflammatory drugs
- Studying triple-negative breast cancer, researchers at Washington University School of Medicine in St. Louis found that some aggressive tumors rely on an antiviral pathway that appears to drive inflammation, widely recognized for roles in cancer, rheumatoid arthritis and other inflammatory diseases.
- The tumors that activate this particular antiviral pathway always have dysfunctional forms of the proteins p53 and ARF, both encoded by genes known for being highly mutated in various cancers.
- The investigators found that the two genes compensate for each other.
- If both are mutated, the tumors that form are more aggressive than if only one of these genes is lost.
- When both genes are lost and the antiviral pathway is activated, patients may benefit from a class of anti-inflammatory drugs called JAK inhibitors, currently prescribed for rheumatoid arthritis.
- In a finding Weber called surprising, the researchers showed that most triple-negative tumors lacking p53 and ARF turn on a pathway involved in the innate immune response to viral infection.
For more information: Cell Reports, DOI: http://dx.doi.org/10.1016/j.celrep.2014.03.026, ARF and p53 Coordinate Tumor Suppression of an Oncogenic IFN-β-STAT1-ISG15 Signaling Axis
10. “Pharmacological Trojan Horse” Fighting Cancer and Resistance to Anticancer Drugs
- Some cancer cells are highly resistant to drugs.
- Two types of MDR are known – inherent drug resistance that exists prior to drug therapy, as well as acquired drug resistance, that is provoked by drug treatment.
- Now researchers at the Technion-Israel Institute of Technology have made a discovery to help fight this phenomenon, namely that drug-resistant cancer cells frequently produce a large number of lysosomes.
- These are membrane- bound structures found in animal cells whose enzymes are capable of breaking down virtually all kinds of biomolecules, including proteins, lipids (fats), nucleic acids, carbohydrates and cellular debris.
- Taking advantage of this unique feature of the production of multiple lysosomes, and the dramatic, irreversible accumulation of certain lipid-soluble drugs bearing light-sensitive properties in these lysosomes, a “pharmacological Trojan horse” was developed that resulted in the destruction of the resistant cancer cells.
- In the meantime, the team are working on the development of a second-generation “pharmaceutical Trojan horse” to selectively target cancer cells by homing in protein receptors present on the malignant cells without harming healthy body cells.
For more information: http://www.technion.ac.il/en/2014/05/pharmacological-trojan-horse/
11. Link between matrix metalloproteinase 1 and circulating tumor cells in early breast cancer
- Matrix metalloproteinases (MMPs) are involved in cancer invasion and metastasis.
- Circulating tumor cells (CTCs) play role in tumor dissemination and are an independent survival predictor in breast cancer (BC) patients.
- The study suggests a link between MMP1 and CTCs with EMT phenotype and support role of MMPs and EMT in tumor dissemination.
For more information: BMC Cancer, 2014, 14:4 72 doi:10.1186/1471-2407-14-472, Matrix metalloproteinase 1 and circulating tumor cells in early breast cancer
12. Cancer immunotherapy market set to grow to nearly $9 billion across major markets in 2022
- The cancer immunotherapy market will experience considerable growth through 2022, increasing from $1.1 billion in 2012 to nearly $9 billion in 2022 (corresponding to 23.8% annual growth) in the USA, France, Germany, Italy, Spain, UK and Japan.
- This impressive growth will be driven by the expected market entry of nine novel immunotherapies – including four novel immune checkpoint inhibitors and five novel therapeutic vaccines – in new oncology indications and/or patient populations, according to a new report from Decision Resources Group.
- Taken together, Bristol-Myers Squibb’s (NYSE: BMY) anti-CTLA-4 agent Yervoy (ipilimumab) and novel immune checkpoint inhibitors that target the anti-programmed cell death-1/programmed death-ligand-1 (PD-1/PD-L1) pathway – including Bristol-Myers /Ono Pharmaceutical’s nivolumab, Merck & Co’s (NYSE: MRK) pembrolizumab (MK-3475), Roche (ROG: SIX)/Genentech/Chugai’s MPDL-3280A and AstraZeneca (LSE: AZN)/MedImmune’s MEDI4736 – will dominate the immunotherapy market and capture a staggering 85% market share in 2022.