Gleevec Halts Spread of Prostate Cancer

Gleevec Halts Spread of Prostate Cancer

There are 7 comments on the Yahoo story from Jun 7, 2006, titled Gleevec Halts Spread of Prostate Cancer. In it, Yahoo reports that:

The cancer drug Gleevec stops the spread of prostate malignancies in mice by attacking the tumor's blood vessels, a new U.S. study reports.

Join the discussion below, or Read more at Yahoo.

gdpawel

Philadelphia, PA

#1 Jun 8, 2006
Gleevec is by far the most successful targeted drug and is vastly superior to other drugs in the treatment of CML. Non-solid cancers are intrinsically sensitive to most any anticancer drug. Besides CML, a rare type of solid abdominal cancer called gastrointestinal stromal tumor (GIST) is commonly associated with mutations in a gene called KIT. The oncogene produces a protein called "kit" that like the Bcr-Abl protein in CML, is inhibitied by Gleevec. Gleevec shrinks many GIST tumors. It has demonstrated significant clinical utility in the treatment of GIST.

Now, it seems that Gleevec may be beneficial for the treatment of prostate malignancies by stunting the activation of platelet-derived growth factor receptors on the cancer cells (PDGF-R). However, as with CML and GIST, resistant cells will evolve and the disease will progress. The development of drug resistance to Gleevec in CML and GIST is not unique, and will happen to prostate disease. Resistance has been described to virtually every anticancer agent examined. The problem of tumor cell evolution.

Unfortunately, the introduction of Gleevec and the other new "targeted" drugs has not been accompanied by specific predictive tests allowing for a rational and economical use of the drugs. Given the technical and conceptual advantages of Cell Culture Drug Resistance Tests (CCDRTs) together with their performance and the modest efficicay of therapy prediction on analysis of genome expression, there is reason for a renewal in the interest for CCDRTs for optimized use of medical treatment of malignant disease. There is a new test that identifies patients who benefit from targeted cancer drugs.
gdpawel

Philadelphia, PA

#2 Jun 10, 2006
Test Identifies Patients who Benefit from Targeted Cancer Drugs

Clinical study results published at the annual meeting of the American Society of Clinical Oncology (ASCO) show that a new laboratory test has accurately identified patients who would benefit from treatment with the molecularly-targeted anti-cancer therapies gefitinib (Iressa) and erlotinib (Tarceva).

The new test, called EGFRx (TM), predicted accurately for the survival of patients treated with the targeted drugs. The finding is important because the EGFRx (TM) test, which can also be applied to many emerging targeted cancer drugs, could help solve the growing problem of knowing which patients should receive costly, new treatments that can have harmful side-effects and which work for some but not all cancer patients who receive them. The test 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

The new test relies upon what is called "Whole Cell Profiling" in which living tumor cells are removed from an individual cancer patient and exposed in the laboratory to the new drugs. A variety of metabolic and apoptotic measurements are then used to determine if a specific drug was successful at killing the patient's cancer cells. The whole cell profiling method differs from other tests in that it assesses the activity of a drug upon combined effect of all cellular processes, using combined metabolic and morphologic endpoints. Other tests, such as those which identify DNA or RNA sequences or expression of individual proteins often examine only one component of a much larger, interactive process.

The whole cell profiling method makes the statistically significant association between prospectively reported test results and patient survival. Using the EGFRx (TM) assay and the whole cell profiling method, can correlate test results which are obtained in the lab and reported to physicians prior to patient treatment, with significantly longer or shorter overall patient survival depending upon whether the drug was found to be effective or ineffective at killing the patient's tumor cells in the laboratory.
gdpawel

Jefferson, MD

#3 Jun 15, 2006
The EGFRx (TM) Assay

The "targets" that the new "smart drugs" go after can be located on the "inside" or "outside" of a cancer cell. The most common targets on the outside are receptors, proteins that help relay chemical messages. And many targets on the inside are enzymes, proteins that help speed up chemical reactions in the body.

According to Chemical & Engineering News, targeted "small-molecule" therapies ruled at the annual ASCO meeting of oncologists. The most exciting results shown came from studies of multitargeted tyrosine kinase inhibitors, small molecules that act on multiple receptors in the cancerous cells, like Tykerb and Sutent. The trend IS away from the monoclonals to the small molecules, a trend which EGFRx (TM) may be able to hasten.

The new EGFRx (TM) assay will test drugs like Iressa, Tarceva, Sutent and possibly Nexavar, because of being small molecules. The monoclonal antibodies like Herceptin and Erbitux are "enormous" molecules. These very large molecules don't have a convenient way of getting access to the large majority of cells. Plus, there is multicellular resistance, the drugs affecting only the cells on the outside may not kill these cells if they are in contact with cells on the inside, which are protected from the drug. The cells may pass small molecules back and forth.

Resistance may be why angiogenesis drugs may be a problem also. Some of these drugs work on anti-angiogenesis (starving tumors by shutting off their blood flow). However, tumors can acquire a blood supply by "three" different mechanisms: angiogenesis, co-option of existing blood vessels, and vasculogenic mimicry. "All" must be inhibited to consistently starve tumors of oxygen. Instead of growing new blood vessels, tumor cells can just grow along existing blood vessels, thus creating resistance to the drug.

Co-option (tumor cells growing along existing blood vessels) cannot be stopped with drugs that inhibit new blood vessel formation. Vasculogenic mimicry (some types of cancers form channels that carry blood but are not actual blood vessels) cannot be stopped with drugs that inhibit new blood vessel formation. The realization that starving tumors by shutting off their blood flow requires that "all three" mechanisms be addressed.

Drugs like Avastin (although a monoclonal antibody) can be tested with EGFRx (TM) because the target of Avastin is not the cells themselves, but rather a hormone (VEGF) secreted by the tumor cells. The Avastin complexes with free VEGF and blocks its action. The EGFRx (TM) test 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. All the more reason to "test the tumor first."
gdpawel

Franklin Park, NJ

#4 Dec 8, 2006
C-kit (KIT) is a protein that indicates GIST (Gastrointestinal Stromal Tumors). The proto-oncogene c-kit and platelet-derived growth factor receptors (PDGFR) are tyrosine kinase proteins that are inhibited by Gleevec in c-kit (CD117) positive GIST. It is overexpressed in a majority of GISTs. Since Gleevec works for some patients with GIST, they think Gleevec will work against prostate cancer.

The c-kit protein may be expressed in prostate cancer and in small cell lung cancer. However, lots of other tumors can express c-kit by immunohistochemistry (IHC), which is an utterly worthless test in this situation. But this expression is only correlated with response to Gleevec in GIST rumors. It is meaningless in other tumors, which is why patients don't routinely test for c-kit in diseases where Gleevec is known to have lousy activity (e.g. prostate cancer, small cell undifferentiated cancer). Gleevec will kill virtually anything if used at a sufficiently high concentration.

There is clinical trial literature in both prostate cancer and in small cell lung cancer with Gleevec. It basically doesn't work very well and the c-kit (CD117) status doesn't correlate one bit with response. There are lots of tumors which are c-kit positive which don't respond to Gleevec. Just like there are lots of tumors which are estrogen receptor positive which don't respond to tamoxifen (e.g. melanoma). And lots of tumors Her2/neu positive which don't respond to Herceptin.

C-kit doesn't correlate with Gleevec response in prostate or small cell.

(Cancer Biol Ther. 2005 Nov; 4 (11): 1270-4; Epub 2005, Nov 18; Cancer Biol Ther. 2005 Dec;5 (12): 1417-8; BJU Int. 2006 Oct;98(4):763-9)

http://www.medicinenet.com/script/main/art.as...
Harry

Schaumburg, IL

#5 Jun 29, 2011
Reduced cost Imatinib(Gleevec,Glivec); [email protected]
Harry

Kingston, NY

#6 Jul 5, 2011
Harry wrote:
Reduced cost Imatinib(Gleevec,Glivec); [email protected]
I would like to know who judged an a price reduction for an outrageously priced medication like Gleevec as funny, spam, or disagreable?
That is certainly an absurd judgement if you are not paying the bill!
Gordon
#8 Sep 23, 2013
I have ordered 2 times from this website PILLSMEDSHOP. COM . I called yesterday the customer care and asked for a discount as i was about to order twice the regular amount.

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