Study suggests patients should be screened before receiving vemurafenib
Different genetic mistakes driving skin cancer may affect how patients respond to the drug vemurafenib, providing grounds to screen people with melanoma skin cancer before treatment, a new study by Cancer Research UK scientists suggests
The findings, published in the journal Genes and Development, show that certain rare gene faults in the tumours of patients receiving vemurafenib may also explain why some patients develop secondary non-melanoma skin cancers.
Vemurafenib works by targeting a common fault in the gene BRAF, called V600E, which is present in at least half of melanomas. The drug stops BRAF from activating a key pathway that drives cancer growth.
But this common fault is not present in all people who develop melanoma and around 18 per cent of patients given the drug go on to develop other, less serious, forms of non-melanoma skin cancer, called squamous cell carcinoma, which need to be surgically removed.
To try and find out why, the University of Leicester-based researchers have been using mice to study a group of rare inherited developmental disorders called RASopathies, which are also caused by faults in the gene BRAF, but not the common fault that causes melanoma.
They studied a specific rare fault in BRAF called L597V, which is found both in melanoma patients and in people with RASopathies.
The rare fault was not found to cause cancer on its own. But when a second gene, called RAS, was faulty too the mice developed cancers similar to those caused by the common fault. However, although the tumours were similar the biology driving the cancers was subtly different.
Crucially this meant that the drug vemurafenib had the opposite effect on cells with the rare fault in BRAF, meaning it actually boosted cancer growth.
Lead author Dr Catrin Pritchard, from the University of Leicester, said: This study shows that the L597V fault only leads to cancer when it happens alongside other faults in the cell, explaining why people with RASopathies dont usually develop the disease. But because this rare fault works in a different way from the common one, vemurafenib has the opposite effect and actually causes secondary tumours, albeit less serious non-melanoma ones. This suggests that people should be screened to see what faults they have before they are given vemurafenib.
Dr Julie Sharp, senior science information manager at Cancer Research UK, said: Cancer Research UK scientists were among the first to discover the link between melanoma and faulty BRAF, and since then drugs like vemurafenib, which block this pathway, have proved to be a major leap forward in the treatment of advanced melanoma. These results, however, could explain why vemurafenib is less effective in some patients who go on to develop secondary cancers. We now need clinical trials to see whether analysing BRAF faults can help predict response to vemurafenib in people, as well as mice.
More information: doi: 10.1101/gad.193458.112
Journal reference: Genes & Development
Provided by Cancer Research UK
- New drug, Vemurafenib, doubles survival of metastatic melanoma patients Mar 01, 2012 | not rated yet | 0
- Study uncovers mechanism by which melanoma drug accelerates secondary skin cancers Jan 18, 2012 | not rated yet | 0
- Panel of melanoma mutations opens door to new treatment possibilities Nov 15, 2011 | not rated yet | 0
- P Rex-1 protein key to melanoma metastasis Nov 22, 2011 | not rated yet | 0
- Response rate high for some patients with metastatic melanoma treated with vemurafenib Mar 16, 2012 | 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 villous adenoma in colon, if there are no villi there
9 hours ago As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 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...
- More from Physics Forums - Medical Sciences
More news stories
Researchers have developed a new drug delivery system that allows inhalation of chemotherapeutic drugs to help treat lung cancer, and in laboratory and animal tests it appears to reduce the systemic damage ...
Cancer 2 hours ago | not rated yet | 0 |
When turned on, the gene p53 turns off cancer. However, when existing drugs boost p53, only a few tumors die – the rest resist the challenge. A study published in the journal Cell Reports shows how: tumors that live even i ...
Cancer 2 hours ago | not rated yet | 0 |
Study leader, Professor John Mathews from the University of Melbourne said this small increase in cancer risk must be weighed against the undoubted benefits from CT scans in diagnosing and monitoring disease.
Cancer 6 hours ago | not rated yet | 0
Cancer survivors are no more likely to stop smoking, cut down on alcohol, or exercise more often than the general population, according to new research published in the British Journal of Cancer today (Wednesday)
Cancer 8 hours ago | not rated yet | 0
Beta-blockers, normally used for high blood pressure, could enhance the effectiveness of chemotherapies in treating neuroblastoma, a type of children's cancer, according to a new study published in the British Jo ...
Cancer 8 hours ago | not rated yet | 0
A new approach for immunizing against influenza elicited a more potent immune response and broader protection than the currently licensed seasonal influenza vaccines when tested in mice and ferrets. The vaccine ...
36 minutes ago | not rated yet | 0 |
Until now, little was scientifically known about the human potential to cultivate compassion—the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.
15 minutes ago | not rated yet | 0 |
A man who had contracted the coronavirus has died in Saudi Arabia, raising the death toll in the kingdom from the SARS-like virus to 17, the health ministry announced on its website on Wednesday.
9 minutes ago | not rated yet | 0
GlaxoSmithKline PLC says it's starting an unusual collaboration with the U.S. government to develop several antibiotics for both bioterrorism threats and bacterial infections resistant to current medicines.
7 minutes ago | not rated yet | 0
What effect does a father's depression have on his young son or daughter? When fathers report a high level of emotional intimacy in their marriage, their children benefit, said a University of Illinois study.
41 minutes ago | not rated yet | 0
Johns Hopkins researchers report that hospitals may be reaping enormous income for patients whose hospital stays are complicated by preventable bloodstream infections contracted in their intensive care units.
37 minutes ago | not rated yet | 0