New strategy to attack tumor-feeding blood vessels
Cancers such as breast cancer, lung cancer and melanoma release the blood vessel growth factor, VEGF, to encourage blood vessels to grow within the tumor, supplying it with nutrients. Tumors can be treated with anti-cancer medications that kill the cancer cells, and anti-angiogenic medications that starve the tumour by attacking its blood supply. The study suggests that a third type of medication, BH3-mimetics, may enhance the tumor-killing effect of anti-cancer and anti-angiogenic medications. Credit: Walter and Eliza Hall Institute
Scientists at the Walter and Eliza Hall Institute have discovered a key molecule needed to kill the blood vessels that supply tumours.
The research team from the institute's Molecular Genetics of Cancer and Cancer and Haematology divisions found that for anti-cancer therapies that target tumour blood vessels to work the death- inducing molecule Bim is required. The finding could lead to improved anti-cancer treatments that are based on a two- or three-pronged attack on both the tumour and its blood supply. The research will be published online in the Journal of Experimental Medicine today.
The growth of solid tumours, such as lung cancer, breast cancer and melanoma, depends on nutrients and oxygen being provided by the tumour blood supply. Cancer cells encourage the growth of blood vessels to feed a tumour by producing the hormone-like protein, vascular endothelial growth factor (VEGF). The research by Drs Edwina Naik, Leigh Coultas and Lorraine O'Reilly, and Professors Jerry Adams and Andreas Strasser showed that VEGF produced by tumours blocks production of Bim in the cells that line the tumour blood vessels.
New 'anti-angiogenic' medications that attack the blood vessels within tumours are showing promise in starving many types of cancers by reducing their blood supply.
In this study, in experimental melanoma, lung cancer and breast cancer models, Bim levels increased in the cells lining the blood vessels when VEGF was depleted by anti-angiogenic drugs, ultimately killing the blood vessel cells. VEGF depletion reduced the number of blood vessels in tumours, making the tumours shrink. However, in mice in which the blood vessels do not express Bim, VEGF depletion did not affect the number of tumour-associated blood vessels, and tumours grown in Bim-deficient mice did not respond to anti-angiogenic treatments.
Dr Strasser said this finding suggests that strategies for treating tumours by attacking the tumour blood supply could be optimised by incorporating drugs called BH3-mimetics that cause cell death by acting like Bim at a molecular level. "Similarly, therapies that increase the amount of Bim in tumour blood vessels could enhance the effects of anti-angiogenic agents," Dr Strasser said.
"BH3 mimetics may have two beneficial effects in cancer therapy. Our previous research had showed they can directly trigger death in tumour cells, particularly when the tumour is also attacked by chemotherapeutic drugs. We now think BH3-mimetics could also impact tumour cells indirectly by killing endothelial cells within tumours.
"This suggests that a promising new approach to the therapy of solid tumours may be to use a three-medication combination of a drug that specifically targets the tumour cell, an anti- angiogenic agent to impair the tumour blood vessels, plus a BH3 mimetic that will help the anti- tumour drug to directly kill the tumour cells and also will help the anti-angiogenic agent to kill the intra-tumoral endothelial cells, which in turn will starve the tumour, causing even more tumour cell death."
Provided by Walter and Eliza Hall Institute
- Innovative method to starve tumors Feb 11, 2009 | not rated yet | 0
- Important mechanism identified in the formation of blood vessels Jan 29, 2007 | not rated yet | 0
- Scientists discover a way to kill off tumors in cancer treatment breakthrough Apr 05, 2011 | not rated yet | 0
- More blood vessels in hormone-resistant prostate tumors Dec 15, 2009 | not rated yet | 0
- A new cancer vaccine starves tumors of blood May 24, 2010 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be a term called "intestinal metaplasia" of stomach
11 hours ago Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
- More from Physics Forums - Medical Sciences
More news stories
Trends in Helicobacter pylori (H. pylori) and smoking explain a significant proportion of the decline of intestinal-type noncardia gastric adenocarcinoma (NCGA) incidence in US men between 1978 and 2008, and are estimated ...
Medical research 57 minutes ago | not rated yet | 0
Widely available in pharmacies and health stores, phosphatidylserine is a natural food supplement produced from beef, oysters, and soy. Proven to improve cognition and slow memory loss, it's a popular treatment for older ...
Medical research 5 hours ago | 5 / 5 (1) | 0 |
Researchers at Emory University have identified a protein that stimulates a pair of "orphan receptors" found in the brain, solving a long-standing biological puzzle and possibly leading to future treatments for neurological ...
Medical research 6 hours ago | not rated yet | 0 |
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
Medical research 6 hours ago | 4.7 / 5 (3) | 0 |
Researchers at the University of Illinois at Chicago College of Medicine will study gender differences in how the heart uses and stores fat—its main energy source—and how changes in fat metabolism play ...
Medical research 9 hours ago | not rated yet | 0
Activating an enzyme known to play a role in the anti-aging benefits of calorie restriction delays the loss of brain cells and preserves cognitive function in mice, according to a study published in the May ...
57 minutes ago | 5 / 5 (2) | 0 |
An experimental sleeping pill from US drug company Merck is effective at helping people fall and stay asleep, according to reviewers at the US Food and Drug Administration, which could soon approve the new drug.
7 minutes ago | not rated yet | 0
A paper recently published in the New England Journal of Medicine and co-written by physicians and scientists at the University of Colorado School of Medicine finds that an important genetic risk factor for pulmonary fibros ...
35 minutes ago | not rated yet | 0
Using the Department of Defense Serum Repository (DoDSR), University of Cincinnati (UC) researchers have identified a number of biomarkers for inflammatory bowel disease (IBD), which could help with earlier diagnosis and ...
36 minutes ago | not rated yet | 0
By studying the roles two proteins, thrombospondin-1 and prosaposin, play in discouraging cancer metastasis, a trans-Atlantic research team has identified a five-amino acid fragment of prosaposin that significantly reduces ...
37 minutes ago | not rated yet | 0
Transparent information on the evidence supporting global recommendations on paediatric medicines should be easily accessible in order to help policy makers decides on what drugs to include in their national drug lists, according ...
57 minutes ago | not rated yet | 0