One challenge that doctors face when treating people with cancer is that they may respond very differently to treatment. Even in people with the same type of cancer, the same treatment may cause some to have their disease completely disappear, while having only a partial response or no effect in others. If researchers can find out how to identify who will benefit from a particular treatment, they will be able to target the use of these treatments and only offer them to people who will benefit.
One form of treatment is immunotherapy, which engages a person’s immune system to fight cancer cells. One immunotherapy, called a checkpoint inhibitor, stimulates the immune system to produce cancer-fighting cells. It has been used successfully to treat a few types of cancer, including lung cancer, and researchers are exploring using this treatment more broadly.
Specific gene can predict response to immunotherapy
A team of researchers from Boston analyzed the genetic material of tumours from people with one particular form of kidney cancer (clear cell kidney cancer) who had taken part in a clinical trial testing checkpoint inhibitors. The treatment worked very well in some of these people, but it did not work in most of them.
When the researchers looked at the genetic material of the tumours, they identified one gene, called PBRM1, that seemed to be important in predicting whether the checkpoint inhibitor would work. People with an inactive version of this gene responded better than people who had active versions of this gene.
The researchers were also able to learn how this gene is involved in the cancer cell’s response to checkpoint inhibitors. They found that the PBRM1 gene starts a complex chain reaction in the cancer cells and their genetic material that results in other genes being activated.
When the PBRM1 gene does not work, the end result of the chain reaction is the activation of other genes that stimulate the immune system to attack. Cancer cells are sensitive to this attack and are eliminated. On the other hand, cancer cells with an active version of the PBRM1 gene are insensitive to immune system attacks, and as a result, don’t respond to checkpoint inhibitors.
Study helps to personalize treatment for kidney cancer
Knowing whether someone will benefit from a treatment before the treatment is given is valuable information. If doctors know that a treatment is not going to work, they don’t need to waste time or money trying the treatment and can instead focus on finding a treatment with a greater chance of success.
For years, doctors have not had a good understanding of why people respond differently to treatments, but genetic research is changing this. Researchers can analyze a tumour’s genetic material and gain valuable insight into potential treatments.
This research also helps to explain the reasons behind the different results in different people. The researchers can then try to determine if the same mechanism at work in kidney cancer’s response to checkpoint inhibitors may also be happening in other types of cancer. This information can help in applying the use of checkpoint inhibitors more broadly.
Eileen Hoftyzer, BSc, and Carolyn Goard, PhD