The term bladder cancer refers to tumors that arise in the urinary collecting system. More than 90 percent of cases in the United States are transitional cell carcinomas in the cells of the bladder’s inner lining. Less common are the squamous cell carcinomas that form in thin, flat cells and adenocarcinomas, which arise in glandular cells. Both of these types typically result from long-term infections or irritation.
The transitional cells that line the bladder form an inner cell layer beginning in the kidneys, extending down the ureters to the bladder and ending at the urethra.
Kidney cancers—known as renal cell carcinomas—arise within the body of the kidney, not the collecting system. According to the American Cancer Society (ACS), more than 57,000 people in the United States are diagnosed with kidney cancer annually. Most of these tumors are known as clear cell carcinomas, which over-produce proteins associated with the formation of blood vessels. It is now known that a mutation in the Von Hippel Lindau (VHL) gene is responsible for most of these cancers.
John Friedberg, MD, was dying. After three months of conventional treatment for metastatic kidney cancer at Stanford, where he was surrounded by colleagues, he was not responding to therapy. He stopped producing red blood cells. He checked out of the hospital and was driven to Rational Therapeutics, where he arranged to have a lymph node removed for an EVA-PCD assay. Read John Friedberg’s story.
Almost 75 percent of people with bladder cancer have a non-invasive form and can be treated with either surgery or radiation. In more advanced cases, chemotherapy is administered to prevent recurrence or control metastatic disease. The drugs with activity in bladder cancer include cisplatin and carboplatin, doxorubicin, Mitomycin-C, 5 FU, cytoxan, interferon, Taxol and gemcitabine. Also, good activity is seen with many drug combinations. When bladder tumors are removed, we can study them in our laboratory to examine the activity of each of the drugs and combinations of interest.
Like bladder cancer, surgery is the most common treatment for kidney cancer. A patient may have an entire kidney removed (the body can function effectively with only one kidney) or may undergo nephron-sparing surgery for a partial kidney removal. As the ACS points out, kidney cancer cells are usually resistant to chemotherapy. Nonetheless, some chemotherapeutic agents (such as vinblastine, floxuridine, 5-fluorouracil (5-FU) and capecitabine) have been shown to help in a small number of patients.
The development of newer classes of drugs known as the VEGF antagonists—that include the monoclonal antibody Bevacizumab and Sunitinib and Sorafenib, as well as the mTOR inhibitors—now offer benefit to a growing number of patients with this disease. Many of these agents can be tested in the laboratory by Ex-Vivo Analysis of Programmed Cell Death (EVA-PCD) to determine efficacy and combination effects.