Breast cancer gene provides vital clue to bowel cancer drug resistance
Having too many copies of a gene linked to breast cancer might be the reason why some bowel cancer patients fail to respond to certain targeted drugs, according to a study published in the British Journal of Cancer.
Researchers – from the Institute of Pathology in Locarno, Switzerland and the Istituto Toscano dei Tumori, Livorno, Italy – looked for extra copies of the breast cancer gene 'HER2' in tumour samples from 170 advanced bowel cancer patients treated with either cetuximab or panitumumab.
These drugs are part of a raft of new targeted treatments directed against tumours that overproduce a protein called Epidermal Growth Factor Receptor (EGFR). They work by preventing EGFR from receiving signals from growth factors, which fuel tumour development.
Healthy cells have 2 copies of the HER2 gene – one inherited from each parent. But in some cancer cells the gene can become copied many times, producing lots of HER2 protein that can drive the disease. The researchers found that measuring the numbers of copies of the HER2 gene in tumour samples could be used to predict resistance to anti-EGFR drugs.
Tumours with consistently high numbers of copies of HER2 throughout– less than one in 20 patients – tended to be resistant to anti-EGFR treatments. These patients had the worst survival rates (4.2 months on average).
While those with the normal number of HER2 genes in their tumour – around 35 per cent of patients – were found to have a good response to these treatments and the best survival rates (13 months on average).
The remaining 65 per cent of patients had a mixture of tumour cells, some of which had extra HER2 genes. These patients only had a partial response to treatment and moderate survival time (9.7 months on average).
Dr Milo Frattini, lead researcher from the Institute of Pathology in Locarno, Switzerland, said: "These results suggest that overproduction of HER2 is not restricted to breast cancer and that it may also drive cancer growth in a significant number of bowel cancers.
"Importantly, because HER2 is a 'sister' molecule of EGFR that regulates a similar set of cancer-causing genes, this could explain how some cancers bypass the EGFR blockade put in place by drugs like cetuximab and panitumumab, causing resistance to these drugs. So in future this could be used to identify patients most likely to respond to anti-EGFR drugs."
Study co-leader, Dr Federico Cappuzzo, from the Istituto Toscano dei Tumori, Livorno, Italy, added: "Our study opens up new options for patients with cancer of the small bowel, by highlighting how existing drugs targeting HER2, such as herceptin or lapatinib, which are currently used in the management of breast cancer, might be extended to these patients."
Dr Julie Sharp, Cancer Research UK's senior science information manager, said: "This research reminds us that cancers often have a variety of different tricks at their disposal when it comes to drug resistance. But, encouragingly, it also suggests that there may be overlap between the faults driving different types of cancer, raising the prospect that combinations of existing drugs could be used to treat a variety of cancers.
"Improving our understanding of the faults driving different types of cancer will in future make it easier to match patients to the treatments most likely to benefit them."
More information: Martin, V., et al. (2013). HER2 gene copy number status may influence clinical efficacy to anti-EGFR monoclonal antibodies in metastatic colorectal cancer patients. British Journal of Cancer DOI: 10.1038/bjc.2013.4
Journal reference: British Journal of Cancer
Provided by Cancer Research UK
- Class of breast cancer drugs could treat other types of cancer Nov 09, 2011 | not rated yet | 0
- Proteins do not predict outcome of herceptin treatment in HER2-positive breast cancer Dec 09, 2011 | not rated yet | 0
- Existing drugs may help more breast cancer patients Dec 07, 2012 | not rated yet | 0
- Herceptin targets breast cancer stem cells Jul 09, 2008 | not rated yet | 0
- Study combines lapatinib with cetuximab to overcome resistance in EGFR-driven tumors May 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
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 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...
- More from Physics Forums - Medical Sciences
More news stories
In recent years, microRNAs (miRNAs) and other non-coding RNAs are small molecules that help control the expression of specific proteins. In recent years they have emerged as disease biomarkers. miRNA profiles have been used ...
Cancer May 24, 2013 | not rated yet | 0
Cancer cells spread and grow by avoiding detection and destruction by the immune system. Stimulation of the immune system can help to eliminate cancer cells; however, there are many factors that cause the immune system to ...
Cancer May 24, 2013 | 5 / 5 (1) | 0
Researchers from London's Kingston University have begun a two-year study which could help prolong the lives of people with colorectal tumours.
Cancer May 24, 2013 | 5 / 5 (1) | 0
Transformative research from Western University has identified new hormones in the body which may suppress breast cancer and stimulate the regression of breast tumors.
Cancer May 24, 2013 | 5 / 5 (2) | 0
(Medical Xpress)—Curtin University researchers have found evidence that targeting specific cells in the body can reverse the effects of cancer on the immune system.
Cancer May 24, 2013 | 5 / 5 (4) | 0
Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...
16 hours ago | 5 / 5 (2) | 5
(HealthDay)—Animals make great companions for senior citizens, but elderly people who always drive with a pet in the car are far more likely to crash than those who never drive with a pet, researchers have ...
8 hours ago | not rated yet | 1
Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...
16 hours ago | not rated yet | 1
Mortality and length of stay are highest in heart failure patients admitted in January, on Friday, and overnight, according to research presented today at the Heart Failure Congress 2013. The analysis of nearly 1 million ...
16 hours ago | not rated yet | 0
(AP)—Department of Justice lawyers have again asked a federal appeals court in New York to delay lifting age restrictions and prescription requirements on an emergency contraceptive popularly known as the morning-after ...
16 hours ago | not rated yet | 0