By Sara Jo Grethlein, MD

Undergoing treatment for cancer can be emotionally and physically difficult, financially stressful and ultimately (for some patients), not as successful as we would hope. Every spring, at the American Society of Clinical Oncology (ASCO), cancer doctors learn about the new proven and upcoming advances in the field.

This year’s conference focused on "Translating Research into Practice". In the 21st century, an understanding of the biology and molecular genetics of cancer cells is proving critical to improved outcomes for patients. A common characteristic of many cancer cells is that they have unmistakable abnormalities in particular chromosomes (though these findings are not present in the patient’s normal cells). This difference offers the opportunity for elegant treatment. Imagine that we can use a "smart bomb" that can distinguish villain from civilian? The ability to preferentially target malignant cells gives us the benefits of limiting toxicity of treatment (if it won’t affect normal cells, then hair loss, low blood counts, heart injury and some of the other worrisome complications of chemotherapy are eliminated), if the toxic side effects are lessened, we can increase drug doses and perhaps deliver a more effective knock-out punch to the tumor.

Distinguishing between cells is not the only option for treatment based on molecular biology. Abnormalities in the function of chromosomes of malignant cells are a target for designer drugs. Perhaps the best known example of this approach is Gleevec (imatinib), a treatment for chronic myelogenous leukemia (CML – a blood cancer that affects predominantly older adults). This treatment targets the Philadelphia Chromosome that results from a piece of chromosome 22 sticking to chromosome 9 in CML cells. Gleevec attacks an enzyme (tyrosine kinase) that produces proteins from the abnormal chromosome. It is remarkably effective, and the side effects are minimal when compared to traditional cancer treatment. After the success of this drug, there has been a dramatic increase in the development of drugs that work by this mechanism.

At this spring’s ASCO meeting an understanding of the biology of kidney cancers was credited with the successful development of four new agents to treat this disease. Two of the new drugs use tyrosine kinases as a target. They are Sorafenib and Sutinib. A third drug, Temsirolimus, inhibits a similar enzyme, mTOR (mammalian target of rapamycin) kinase. A recently published trial of Temsirolimus demonstrated it improved survival when compared with Interferon (the former standard of care). On the basis of these results, the drug was FDA approved May 31, 2007. A trial of Sorafenib versus placebo in patients, who had disease progression on first line therapy, showed a doubling of progression free survival. The outcomes are still far from ideal, but represent significant evidence of progress. The newest weapon in the arsenal against kidney cancer is Bevacizumab (Avastin). This exciting drug blocks VEGF (vascular endothelial growth factor) and has been demonstrated to improve outcomes in breast cancer and colon cancer. A trial presented June 2, 2007, demonstrated a doubling in disease free survival for patients with kidney cancer when this agent was added to the old standard treatment (interferon).

The future looks bright for the development of new agents to treat kidney cancers. You see, kidney cancer is not a single disease; it is a family of different diseases in which researchers have already identified many abnormal genes (such as the Von-Hippel-Lindau (VHL) gene, hereditary papillary renal cell carcinoma (HPRCtype 1 gene), Birt Hogg Dubé (BHD gene) and hereditary leiomyomatosis RCC (HLRCC type 2 papillary; fumarate hydratase gene). These are no longer interesting laboratory findings, but opportunities for disease specific cancer treatments.

Proof exists that molecularly based cancer therapies can enhance survival for patients when added to (or in some cases substituted for) traditional treatments. The next few years will be exciting as we push the boundaries of our current knowledge of cancer biology and translate it into more effective, less toxic therapy for patients. Unfortunately, it will take more than science alone to lessen the financial stress of these new drugs which can be extremely costly – Gleevec can cost upwards of $30,000 per year.

Sara Jo Grethlein, MD, earned her MD from SUNY, Downstate in Brooklyn, NY. She is triple boarded in Internal Medicine, Hematology and Medical Oncology, having trained in these fields at Barnes Hospital, Washington University in St. Louis, MO. She is currently serving as Associate Dean for Graduate Medical Education at SUNY Upstate Medical University in Syracuse, NY.

This article originally appeared in the September 2007 issue of aakpRENALIFE.