What is a research trial?

Medical research studies involving people are called clinical trials. Clinical trials involving cancer look at

1 Preventing cancer-drugs vitamins food which may reduce risk.

2 Screening for people at higher thans average risk or the general population

3 Diagnosing cancer-new tests or scans

4 Treatments-new drugs or combinations of drugs; new ways of giving treatments, new types of treatments.

5 Controlling symptoms-new drugs or complementary therapies.

The aim of trials.

Trials try to find out if a new treatment or procedure

1 Is safe

2 Has side effects

3 Works better than currently used treatment

4 Helps you feel better.

New treatments have to be thoroughly tested. A new drug ,for example is investigated in the laboratory. If it looks promising, it is carefully studied in people.

Different types of trials.

There are four phases of clinical trials.Each treatment being tested has to go through all these phases.

Phase 1 trials look at whether a trial tretarment is safe, or has any harmful effects. For trials on new drugs the correct dose to give will also be tested.

Phase 2 trials look at whether a treatment works . Only a treatment that has got through these two phases will go into phase 3 testting.

Phase 3 trials test a new treatment against the existing standard treatment. If it gives better results it may become the new standard treatment.

Phase 3 trials also look at how well the treatment works, and any side effects. The researchers may look at the impact a treatment has on you-how often do you have to  trav el to the hospital, for example. Studies of impact and side effects are sometimes called quality of life studies Most well planned phase 3 medical research includes an investigation of quality of life.

Usually a new treatment has to go through a few phase 3 trials before doctors are confident enough to accept it as new standard treatment. One good trial result could happen by chance, or because a trial was not well designed. This is not likely if several trials have the same result.

There are now phase 4 trials. These are carried out after a drug has been licensed. They collect information about side effects, safety and long term risks and benefits of a drug.

Clinical will not all result in new and better treatment. Some will discover that the treatment tested does not work, or that its side effects are worse than existing treatments. To researchers, doctors and in the end for patients, it is still useful to be able to rule something out.

From the Cancer Help UK website. Updated January 2006.

Scientists have discovered how a faulty gene can increase the risk of kidney tumours.

Imperial College London researchers looked at cells from people with VON HIPPEL LINDAU syndrome - an inherited condition.

They found the cells behaved as if they had too little oxygen-setting off a chain of events which can lead to them becoming cancerous.

Experts said the discovery, detailed in the journal Cancer Research, could pave the way for new treatments.

The research group has discovered a potential mechanism by which mutant VHL could contribute to tumour development. Professor John Toy. Cancer Research UK.

Over 6,600 people are diagnosed with kidney cancer each year in the U.K.  and approximately 36,000people in the United States are diagnosed annually with kidney cancer. The average age of onset of symptms of kidney cancer is age 62 in the general population, or 42 among people with a familial syndrome like VHL.

The researchers looked at people with VHLS which increases a persons risk of developing benign or malignant  tumours in the kidney - as well as rare forms of tumour in other parts of the body- because of faults in the VHL gene.

The gene normally safeguards against cancer, suppressing tumour growth.

People in familes with the VHL gene have a 50% chance of inheriting the faulty gene-and if they do a 70%chance of developing kidney cancer at some stage in their lives.

Lack of oxygen.

Until now, it has not been clear how faults in VHL can lead to the development of kidney cancer.

The researchers found that kidney cells with faulty VHL were lacking a normal protein molecule, called e-cadherin, which contributes to normal cell behaviour.

They found the cells behaved as if they were receiving less oxygen than they really were.

To combat this perceived lack of oxygen, the cells raised a chemical signal called HIF (hypoxia-inducible factor)

HIF causes the kidney cells to switch off  e-cadherin.

Normally , the e-cadherin protein molecule plays an important role in helping cells to stick together to form healthy tissues.

This loss of molecule results in a communication breakdown between neighbouring cells.

Cells then acquire important features of cancer , as low oxygen levels are common in tumours.

E-cadherin is also lost in several forms of cancer, including breast cancer.

Mechanism.

Professor Patrick Maxwell, who led the research, said 'it is very powerful scientifically to be able to study cells before they become cancerous, as it helps us to understand how tumours develop.'

Kidney cancer is usually detected late, when the only available option is radical surgery.

Investigating cells before they develop into tumours could help us find a way to detect and treat kidney cancer earlier.

Professor Maxwell added "We don't think loss of e-cadherin is the only thing responsible for the development of kidney cancer"

"In fact there are probably many more factors involved, our next task is to find out what these are, and work out the best way to prevent this disease from forming in the first place.

Professor John Toy, Medical Director of Cancer Research UK, said " By examing the relationship between oxygen levels and e-cadherin, the research group has discovered a potential mechanism by which mutant VHL could contribute to tumour development."

"This is extremely interesting research as it could pave the way for new treatments and offer hope to patients with the VHL syndrome."

The work was funded by Cancer Research UK, the Medical Research Council and the Wellcome Trust.

Stories from BBC News.

Published 2006/04/02.

Dr.Don Bellgrau of Colorado University. 

We all know that vaccinations can protect us from infectious diseases like polio, but is it possible to develop a vaccine against cancer? .Vaccines work by introducing the infectious agent to the body to help our immune systems to develop its defences against the infective agent. Ironically, cancer deceives the immune system into thinking they are not harmful, so the body does not mount its full defence system.

Dr. Bellgrau and his team, have developed a system for tricking the immune system into seeing a dangerous situation worthy of mounting a full defence. This response should enable the body to destroy the tumour. Dr Bellgrau hopes to provide proof   that individualised vaccines may be made specific for VHL mutation types, to treat renal cell carcinoma.

Dr. Susanne Schlisio. Cancer Research Institute. Boston.

Key developments in the development of pheochromocytomas (pheos.)

Pheos arise from the same primitive cells that give rise to parts of the nervous system, called neural crest cells. Some families are at high risk of developing pheos because they have alterations in specific genes, one of them being the VHL gene. It has been discovered that these genes play an essential role in determining whether neural crest cells live or die. Neural crest cells which should have died as part of normal development in the feotus, escape this death sentence and go on to cause tumours in later life. The team showed that one gene 'EgIN3'  promotes the death of neural crest cells, and inhibition of this gene has the opposite effect. They are trying to understand the mechanism by which EgIN3 causes cell death, because this understanding might, in time, allow us to induce pheo cells to die in patients, which should shrink existing tumours, and prevent newpheo formation.

Taken from the VHLFA report 2006, with thanks to Joyce Graff.

December 3rd 2006.

Mary Weetman.