Combination of drugs and radiotherapy used in search for better cancer outcomes
Posted: 22nd Jan 18 9:59 AM
Researchers on the hunt for better results in the search for a cure for cancer turn to radiotherapy for answers.
Radiotherapy has been around for many years and is often very effective, but researchers are still discovering new ways to use it.
One new initiative is the testing of new drugs alongside the use of radiotherapy.
“The aim is to increase the chance of a cure by making the radiotherapy more effective at killing cancer cells,” says Professor Anthony Chalmers, a Cancer Research UK-funded radiotherapy expert at the University of Glasgow.
Research is currently focused on finding drugs that enhance the effects of radiotherapy on cancer cells, while leaving normal, healthy cells unaffected.
Professor Kenneth Harrington, joint head of the Division of Radiotherapy and Imaging at The Institute of Cancer Research, London, says that the precision of radiotherapy will have a big part to play in this.
“The more precise we get in radiation delivery, the better opportunities we have to combine some of the new smart drugs with radiation,” he says.
High tech radiotherapy methods that deliver as little radiation to normal, healthy tissues as possible, while maintaining or escalating the dose to the tumour, are ideally suited for these combinations, with the aim of decreasing the chances of side effects.
Various studies are already underway to test if certain drugs can make radiotherapy more effective, or if radiotherapy can make other drugs yield better results.
Blocking the repair of cancer cells
Radiotherapy causes damage to DNA inside both cancerous and healthy cells. If cells can’t repair this damage, they die. This is good news if cancer cells are dying, but not if it is healthy cells that are affected.
Some cancer cells are reliant on specific processes to repair the damage caused by radiotherapy. It is the knowledge of how cancer cells respond to radiotherapy that researchers are hoping to exploit in combination with targeted drugs.
“The idea is that the radiation triggers DNA damage, the tumour relies on a specific pathway to fix that DNA damage and you come in with a drug that blocks that pathway,” says Professor Harrington. “Normal cells have other backup pathways they can use to get around the drug, whereas the tumour is absolutely addicted to this pathway, and you’ve blocked it with a drug.”
It is important to work out which patients will benefit from using these drugs alongside radiotherapy. Identifying and measuring molecules that distinguish between normal and cancer cells – called biomarkers – is one way of doing this.
As part of these current trials, researchers will collect tumour and blood samples from patients with the aim of identifying biomarkers to predict who might benefit in the future.
Vaccinating the patient
“There is a growing interest in a completely different approach, which is to use radiotherapy to boost the effects of drug treatments,” says Professor Chalmers.
The best example of this is using radiotherapy in combination with immunotherapy.
A radiation hit to a cancer can sometimes affect not only the tumour itself, but also distant sites of the disease (metastases) that haven’t been irradiated. This is known as the abscopal effect.
When radiotherapy kills tumour cells, they release molecules that alert the immune system. Immune cells can then potentially target the original tumour, as well as other cancer cells that have spread around the body.
Professor Harrington describes this as using radiotherapy to “vaccinate” the patient against their own disease.
However, the abscopal effect is quite rare.
So, researchers are looking at how immunotherapies such as checkpoint inhibitors can provide a boost. These drugs release the brakes on the immune system so that it can better fight the tumour.
“Not surprisingly, there’s huge interest in this abscopal effect of radiotherapy,” says Professor Chalmers. “Researchers are working to identify the best dose and timing of radiotherapy to use, and the best drugs to combine it with.”
Can immunotherapy help mesothelioma patients?
Immunotherapy is a potential life-extending treatment for victims of mesothelioma whose tumours have progressed after exhausting other forms of treatment. Although it is not effective for everyone, studies have shown that a significant proportion of patients derive some clinical benefit. It is currently impossible to predict in advance which patients will benefit, so that it is appropriate that, wherever the victim remains sufficiently well, an initial course of the treatment (usually over 12 weeks) is tried. Where there is a response, the treatment will be continued until the tumour progresses.