What’s New in Kidney Cancer Research and Treatment?

Research on the treatments for renal cell carcinoma is now being done at many medical centers, university hospitals, and other institutions across the nation. The American Cancer Society supports research into the causes, detection, diagnosis, and treatment of kidney cancer.

Genetics

Scientists are studying several genes that seem to play a part in changing normal kidney cells into renal cell carcinoma (RCC).

For example, problems with the VHL tumor suppressor gene are found in most clear cell RCCs. This allows other genes such as the hypoxia-inducible factor (HIF) gene to be activated when they shouldn’t be, which drives a cell toward being cancerous. Some newer treatments focus on attacking this cellular pathway.

Researchers now also have a better idea of the gene changes responsible for some other forms of RCC. Doctors are trying to determine which treatments are most likely to be effective for certain types of RCC. This information can also be used to develop new treatments.

New approaches to local treatment

High-intensity focused ultrasound (HIFU) is a fairly new technique that is now being studied for use in kidney cancer. It involves pointing very focused ultrasound beams from outside the body to destroy the tumor.

Ablation with cryotherapy or radiofrequency ablation (RFA) is sometimes used to treat small kidney cancers. Research is now under way to determine how useful these techniques are in the long term and to refine them further.

Targeted therapies

Because chemotherapy is not very effective against advanced kidney cancer, targeted therapies are now usually the first-line option to treat kidney cancers that cannot be removed by surgery. At this time they are usually given separately. Clinical trials are now under way to see if combining these drugs, either with each other or with other types of treatment, might be better than using them alone.

Many new targeted therapies drugs are now being tested as well, with including cediranib and trebananib. Some of these are already showing promise in early clinical trials.

The potential roles of giving targeted drugs before and after surgery (called neoadjuvant and adjuvant therapy, respectively) are also being studied. The hope with these studies is to increase cure rates, and perhaps (in the case of neoadjuvant therapy) to shrink tumors to allow for less extensive surgery. This could help people retain more of their normal kidney function.

Along with finding new medicines and looking at the best way to combine and sequence existing ones, a major area of research is finding better ways to select the best treatment for each person. That is, finding factors about a person’s cancer that make it more likely to respond to a certain medicine. This can increase the chances of being helped by a therapy and lower the chances a person will get a treatment that is unlikely to help them (and which could still have side effects).

Immunotherapy

Kidney cancer seems to be one of the cancers most likely to respond to immunotherapy, which is treatment that boosts the body’s immune response against cancer cells. Clinical trials of many new immunotherapy methods are being tested. Basic research is now being directed toward a better understanding of the immune system, how to activate it, and how it reacts to cancer.

Drugs that block PD-1 and PD-L1

Cancer cells use natural pathways in the body to help avoid being detected and destroyed by the immune system. For example, they often have a protein called PD-L1 on their surface that helps them evade the immune system. New drugs that block the PD-L1 protein, or the corresponding PD-1 protein on immune cells called T cells, can help the immune system recognize the cancer cells and attack them.

Several drugs that block these proteins are now in development, and some have shown a lot of promise against kidney cancer. For example, nivolumab (Opdivo) is now approved for use in people with advanced kidney cancer, as it has been shown to help some people live longer. Large studies of several other new drugs are now being done.

Vaccines

Several types of vaccines for boosting the body’s immune response to kidney cancer cells are being tested in clinical trials. Unlike vaccines against infections like measles or mumps, these vaccines are designed to help treat, not prevent, kidney cancer. One possible advantage of these types of treatments is that they seem to have very limited side effects. At this time, vaccines are only available in clinical trials.

There are several ways to create vaccines that might stimulate the immune system:

• In one approach, cancer cells (removed during surgery) are altered in the lab to make them more likely to cause an immune response and are then returned to the body. In another approach, a special virus is altered so it is no longer infectious, but it carries a gene for a protein often found on cancer cells. Once the virus is injected into the body, the hope is that the protein will cause the immune system to react against cancer cells anywhere in the body.
• In another approach, immune system cells are removed from the blood. The cells are treated with cytokines and exposed to killed tumor cells to make cells called dendritic cells. These cells are then injected into the body to stimulate the immune system to fight the cancer. Early results have been promising, but more studies are needed.

Combining vaccines with targeted agents or other agents to help them work better is also being studied.

Bone marrow or peripheral blood stem cell transplant

In people with advanced kidney cancer, the person’s own immune system is not effectively controlling the cancer. Another approach to immunotherapy is to try to use someone else’s immune system to attack the cancer cells.

First, very early forms of immune system cells (called stem cells) are collected from a compatible donor, either from their bone marrow or their blood. The person with cancer is then treated with chemotherapy drugs, either in lower doses (called a mini or non-myeloablative stem cell transplant) to suppress the immune system or in higher doses to cause more severe damage to the immune cells and other components of the bone marrow. They are then given the donor stem cells to try to build a new immune system that will be more likely to attack the cancer cells.

Some early studies of this technique have been promising, finding that it may help shrink kidney cancers in some people. But it can also cause major complications, and side effects can be severe. Until more is known about its safety and usefulness, it will probably only be available in clinical trials.

Learn more about the procedure in Stem Cell Transplant (Peripheral Blood, Bone Marrow, and Cord Blood Transplants).