Stutent: new wonder drug?

[eric]

http://www.earthtimes.org/articles/show/7876.html
New wonder drug can combat two or more cancersPosted on : Mon, 31 Jul 2006 12:12:00 GMT | Author : Alan Cross
News Category : Health
This day sees the launch of Pfizer's unique drug Stutent which has been formulated to fight against two or more types of cancers. This is the first time that a drug capable of battling multiple cancers has been developed and physicians see it as a ray of hope for several hundred patients who do not respond to conventional treatment.

The drug has already received licenses for treating kidney cancer and cancers of the gastro-intestinal system. Early trials however, hint that it would also work for inhibiting cancers of the lungs, pancreas and breast. The method of functioning of the drug is along the lines of an earlier drug Glivec – it hampers a particular enzyme due to which the multiplication of cancerous cells is stopped. Another process that it follows is starving the tumor of nutrition by denying growth of blood vessels. Both these processes work in synergy, thereby significantly checking progression of cancer.
Martin Gore, Professor of Cancer Medicine at the Royal Marsden Hospital, London said that results of theclinical trials were very encouraging – 42% of patients who took the drug benefited from it. This launch is estimated to be a boon for approximate 6,600 kidney cancer and 900 GIST new cases annually in UK.

Mick Coleman, a former lecturer was one of the patients on whom the drug was tested and he has only good things to say about it. This 49-year-old man was diagnosed with kidney cancer in 2001 and remained cancer-free for two years after the organ was removed. However, later there were tumors discovered on his lungs, following which he underwent immunotherapy. Soon his body became resistant to this treatment and Coleman enrolled to try Sutent. He states that the drug gave him several months of good quality life and emphasizes that all cancer patients should benefit from it.

What remains to see how accessible it will finally become since it costs around £2,400 per month. Added, this so far can be recommended only after patients have failed to benefit from other treatments and drugs.

[al from Canada]

Eric,
I have been following this drug for about a year, I think there are some in our group who may benefit from this targetted therapy; just have to find an onc who'll take the next step.
Al

[gdpawel]

The new “smart” drugs are a really exciting element of cancer medicine. One of the new molecularly-targeted cancer drugs is Sutent. It is a “multi-targeted kinase inhibitor.” A drug that inhibits several proteins involved in triggering replication in cancer cells. Basically, inhibits various kinases, a type of enzyme that transfers phosphate groups from high-energy donor molecules to specific target molecules.

Sutent (sunitinib) is an inhibitor of multiple protein kinases, platelet-derived growth factor (PDGFR), vascular endothelial growth factor receptors (VEGFR), stem cell factor receptor (KIT), FMS-like tyrosine kinase (Flt3), colony stimulating factor (CSF-1R), and the neurotrophic factor receptor (RET). Because these proteins are involved in both tumor proliferation and angiogenesis, Sutent has both anti-tumor as well as anti-angiogenic properties. In addition, because Sutent inhibits multiple kinases, it possesses activity against multiple types of tumors.

Sutent can be used as a second-line drug for tumors that are non-responsive to Gleevec. The proto-oncogene KIT, a tyrosine kinase that is inhibited by Gleevec, is overexpressed in a majority of GISTs. Some patients have suffered relapses due to acquired point mutations in KIT, which prevents Gleevec from binding to the protein. Similar mutations have been characterized in EGFR from Iressa-resistant lung cancer patients.

The largest group of kinases are Protein kinases, which act on and modify the activity of specific proteins. So people will try and get some sort of gene-based test to measure the expression-mutation of these kinases. But something more elemental is going on. Does the drug even enter the cell? Once entered, does it immediately get metabolized or pumped out, or does it accumulate?

The new EGFRx ™ Anti-Tyrosine Kinase Profile Assay measures the net effect of everthing which goes on (Functional Profiling). Are the cells ultimately killed, or aren’t they? In photomicrographs (two magnifications), it is fairly easy to see that some clones of tumor cells don’t accumulate the drug. These cells won't get killed by it. Sutent is conveniently pigmented, brilliant yellow. It is easy to see which cells have taken it up. But you wouldn’t pick this up with an assay which only measured the kinases themselves.

Normal chemotherapy kills both cancer cells and healthy normal cells (mainly rapidly-dividing cells). Oncologists try to minimize damage to normal cells and to enhance the cell-killing effect on cancer cells. Too often, this delicate balance is not achieved.

Targeted therapy drugs interfere with specific molecules (receptors and enzymes inside and outside a cancer cell). By focusing on these molecular and cellular changes, targeted cancer drugs go after the “target” in these cells, rather than just all cells. Because of this, “targeted” drugs may be more effective than current treatments, and may be less harmful to normal cells.

Functional profiling can discriminate between the activity of different “targeted” drugs and identify situations in which it is advantageous to combine the “targeted” drugs with other types of cancer drugs. Because these new “smart” drugs will work for “some” but not “all” cancer patients who receive them, whole cell profiling can accurately identify patients who would benefit from treatment with molecularly-targeted anti-cancer therapies.

Not only is this an important predictive test that is available, but it is also a unique tool that can help to identify newer and better drugs, evaluate promising drug combinations, and serve as a “gold standard” correlative model with which to develop new DNA, RNA, and protein-based tests that better predict for drug activity.

This kind of technique exists, and might be very valuable, especially when active chemoagents are limited in a particular disease; it makes more sense than ever to test the tumor first. Afterall, cutting-edge techniques can often provide superior results over tried-and-true methods that have been around for many years.

The EGFRx ™ Anti-Tyrosine Kinase Profile Assay is the only assay that involves direct “visualization” of the cancer cells at endpoint. This allows for accurate assessment of drug activity, discriminates tumor from non-tumor cells, and provides a permanent archival record, which improves quality, serves as control, and assesses dose response in vitro.

Source: Cell Function Analysis