New therapeutic target to combat liver cancer discovered
Spanish researchers at CIC Biogune, the Cooperative Centre for Research into Biosciences and led by Dr. Maria Luz Martinez Chantar, have found a strong relationship between high levels of Hu antigen R (HuR) protein and the malignancy of Hepatocellular Carcinoma, through a novel molecular process in the investigation of this pathology and known as neddylation. The project provides new opportunities for making advances in the quest for personalised therapeutic applications in the treatment for Hepatocarcinoma.
Hepatocellular Carcinoma (HCC) is the cause of most liver cancers, the fifth most frequent cancer worldwide and the third after lung and gastric cancers. HCC is a tumour with a poor prognosis, even in developed countries; its incidence is similar to its death rate, most patients dying within months of diagnosis, despite diagnostic and therapeutic advances. It is a highly heterogeneous tumour and so the scientific community is redoubling its efforts to establish personalised and highly specific therapeutic targets.
Researchers from the Metabolomic Unit at CIC bioGUNE and led by Dr. Martinez, have gone one step further with this type of tumour and have revealed a hitherto unknown molecular mechanism that is involved in the development of CHC, showing that the malignancy of this illness may be linked to the overexpression of the HuR protein.
The research work, published in the Hepatology journal, and which has obtained a mention in the Cancer section of the prestigious Nature Reviews Gastroenterology & Hepatology journal, showed the relation between high levels of HuR protein and the malignancy of Hepatocellular Carcinoma by means of a molecular mechanism neddylation - totally novel in these kinds of tumour and effectively opens up new opportunities for the future development of potential therapeutic applications for patients with this pathology. The route also proved to have an application in cancer of the colon, given the high correlation between both types of tumour.
"Neddylation is an enzymatic reaction which, in the biological context, avoids the degradation of the protein modified with the NEDD8 molecule. Just as the ubiquitination marks the proteins to order them to be degraded, neddylation marks them in order to stabilise them and, in theory, these proteins are important for the tumour to proliferate and develop", explained Dr Martínez, lead researcher in the project.
In this way, the strategy followed has been to maintain the HuR protein at high levels of expression through its modification by neddylation, thus encouraging its proliferation and the malignancy of the HCC, in such a way that, "when we block the neddylation action or regulate the levels of HuR protein in liver tumours and in in vitro and in vivo hepatoma lines, cell death is induced and tumour regression takes place", stated Dr Martínez.
The options of conventional oncological treatment for Hepatocellular Carcinoma are limited, given that it is a highly chemoresistant tumour, usually arising from a cirrhotic liver. Approximately 40% of the patients diagnosed with HCC are in at an advanced stage and whose short-term prognosis produces a survival rate of 1 year in 29% of cases and of 2 years in 16%. This neoplasia is a unique situation in oncology and, despite its high incidence and poor prognosis, has not had an effective therapeutic option to date. A possible explanation for this is the wide-ranging heterogeneity in the molecular mechanisms involved in the development of this tumour.
The following step in this long and complex process of research is to find a potential therapeutic application for the formula found. This is why Dr Martínez has come to an agreement with the pharmaceutical Millenium: the Takeda Oncology Company to apply new neddylation inhibitors, marketed by this company and currently being tested in other types of tumours, to in vivo Hepatocellular Carcinoma models (mice), in order to explore this new therapeutic solution.
"Now that we have discovered that neddylation can play an important role in the development and progress of HCC, the next step is to undertake an in-depth study of possible therapeutic applications", concluded Dr Martínez.
Provided by Elhuyar Fundazioa
- c-Met may be a biomarker for metastatic hepatocellular carcinoma Sep 28, 2010 | not rated yet | 0
- Personalized treatment may help some liver cancer patients Oct 22, 2010 | not rated yet | 0
- Recurrence of hepatocellular carcinoma 12 years after the initial diagnosis May 06, 2010 | not rated yet | 0
- Apoptotic mechanisms of octreotide on HepG2 Jan 31, 2011 | not rated yet | 0
- A potential chemotherapeutic drug to treat hepatocellular carcinoma Jul 30, 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
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 7 hours ago | 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 7 hours ago | not rated yet | 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 11 hours ago | 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 11 hours ago | 5 / 5 (1) | 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 12 hours ago | 5 / 5 (3) | 0
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
5 hours ago | 5 / 5 (1) | 0 |
(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...
11 hours ago | 5 / 5 (3) | 0 |
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
8 hours ago | 5 / 5 (1) | 0 |
Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...
8 hours ago | 5 / 5 (2) | 0 |
Talking on a hands-free device while behind the wheel can lead to a sharp increase in errors that could imperil other drivers on the road, according to new research from the University of Alberta.
5 hours ago | not rated yet | 0
Kate O'Reilly's spring allergy survival kit includes the usual stuff - nasal sprays, allergy pills and a box of tissues. This season, she's added a new weapon to her line of defense: an app on her smartphone.
6 hours ago | not rated yet | 0