Each year in the United States, more than 60,000 people are diagnosed with a type of kidney cancer called, "renal cell carcinoma," or RCC. The incidence of RCC has been increasing at a rate of about 2% every year. About 13,000 patients die each year of this disease. When diagnosed in its early stages, RCC may be cured by surgery. However, in approximately 30% of the patients, the cancer cells have already spread, or "metastasized," to other organs by the time the patient is diagnosed. For these patients, treatment options are limited: metastatic kidney cancer is resistant to chemotherapy, radiation, hormone therapy, and most other available treatments. There are a few drugs that patients initially may respond to; however, drug resistance eventually sets in. As a result, the average survival time of patients with metastatic kidney cancer is 12 months, and only 11.1% will survive for longer than 5 years. In order to extend the lives of these patients, scientists must develop new treatments to overcome drug resistance.

Here are just a few highlights of what the National Foundation for Cancer Research is doing to help fight kidney cancer.

A New Vaccine for Kidney Cancer
Howard Kaufman, M.D.
NFCR Project Director
Columbia University, New York, NY

The reason that our immune system cannot fight cancer is that it cannot distinguish cancerous cells from normal cells. Instead of killing the tumor, the immune system tolerates the tumor's growth, allowing it to spread and slowly take over the body, eventually killing the patient.

One solution to this problem is to find something that "wakes up" the immune system and allows it to recognize and kill cancer cells. For some kidney cancer patients, this "something" is called, "interleukin-2" (IL-2), a "natural product" of the body which activates immune cells to kill cancerous tumor cells. However, IL-2 is effective in less than 20% of metastatic RCC patients; the other 80% do not respond to it. Thus, a more powerful immunotherapy which could benefit more patients must be developed.

Fortunately, NFCR Scientist Howard Kaufman, M.D., at Columbia University, has successfully developed a kidney cancer vaccine that teaches the immune system to recognize and kill cancer cells. Dr. Kaufman recognized that many cancer cells have something that makes them diff erent from normal cells: unique proteins (antigens) on their surface which are not present on normal cells. A cancer vaccine which contains a cancer-specific antigen can be used to teach the immune system to recognize those antigens and to reject any cells with those antigens. With this vaccine, the immune system can now overcome its tolerance of cancer cells and eliminate them.

Dr. Kaufman's vaccine, named MVA-5T4, presents a tumor-specific antigen, 5T4, which is identified in almost 100% of kidney cancer cells and 0% of normal cells. This vaccine worked very well in eliciting tumor-specific immune responses in tumor models. Experiments showed that the expression of 5T4 in tumor models triggers immune reactions that target only kidney cancer cells, but not normal kidney tissue. Th is could significantly improve treatment
efficacy and reduce side effects. In addition, because MVA-5T4 works in a different way than IL-2, Dr. Kaufman's research team also tried pairing them together and found that combining the two agents was more powerful than using either one alone.

These very successful and exciting results have moved Dr. Kaufman's research into clinical phase studies. Currently, Dr. Kaufman and his team are conducting a Phase I clinical study using MVA-5T4 in patients with metastatic RCC. They will determine the cancer-killing effects of the vaccine, test its safety, and closely observe any side effects it may cause in the patients. If successful, this new vaccine will be further studied and may soon be brought to more patients, helping them in the fight against kidney cancer. This vaccine may also help fight other types of cancer: the 5T4 tumor antigen is also expressed on colorectal and breast cancer cells but not their normal counterparts, which means there is a chance that this new vaccine may work for colorectal and breast cancer patients as well.

Discovering the Cause of Drug Resistance
Bin Teah Teh, M.D., Ph.D.
NFCR Project Director
Van Andel Research Institute, Grand Rapids, MI

Cancer is ultimately a disease of genes: it is the abnormal expression of certain genes that provokes a cell into uncontrollable growth (resulting in a tumor), and researchers believe that it is also the abnormal expression of certain genes that causes tumors to eventually become drug-resistant. NFCR Scientist, Bin Teah Teh, M.D., Ph.D., Distinguished Scientific Investigator at the Van Andel Research Institute, is one of the world's leading scientists seeking solutions to kidney cancer drug resistance from genes.

As his first step, Dr. Teh and his team have collected 500 primary and metastatic kidney cancer tissue samples and obtained gene profiles from each sample. (A gene profile is a collective view of gene activities). Next, Dr. Teh's team will compare the 500 gene profi les in search of genes that are related to drug resistance. Th e team will pin-point the group of genes that show distinguishable activities in the drug resistant tumor samples. Because each individual tumor has a different gene profile, it is critical to have a large amount of tissue samples for analysis in order to obtain reliable results.

The tremendous resources that Dr. Teh's team has access to are not available anywhere else. This provides an invaluable advantage in seeking common genes that are related to, or directly account for, drug resistance in metastatic kidney cancer. Upon selecting out a group of genes for drug resistance, Dr. Teh's team will further verify their results and pinch out the real "bad genes" through intensive verification experiments.

Dr. Teh's approach is highly promising in finding the fundamental causes of drug resistance in kidney cancer. The potential discovery of drug resistance genes will lead to new biomarkers that can predict drug response in kidney cancer patients. By knowing in advance which patients' tumors are most likely to resist certain drugs, oncologists may be able to prescribe more effective treatments to the patients in the first place, extending or even saving more patients' lives. In addition, the discovered drug resistance genes will be used as novel drug targets for the development of more effective drugs, which may eventually overcome the entire problem of drug resistance in kidney cancer.

Dr. Teh's research, if successful, will contribute significantly to the understanding of drug resistance, and in the long run, lead to tremendous improvements in kidney cancer treatment.  To help support his work, click here.