While it has been reported to have saved more than 100,000 lives, Gleevec is now saving more children with a dire leukemia (Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) ), as well as preventing disease progression with long term use in adults with chronic myeloid leukemia (CML).

Such were the data reported by Oregon Health & Science University (OSHU) at the recent annual meeting of the American Society of Hematology:

“Data at this weekend’s meeting continues to show how much Gleevec has completely changed the outlook for so many, many patients facing cancer.

Researchers delivered news that Gleevec has been shown to improve outcomes for children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).”

Gleevec is a product of Novartis.

Find more details from OHSU.

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More Good News From Gleevec

Developed by Novartis Pharmaceuticals, Gleevec is approved by the U.S. Food and Drug Administration for the treatment of chronic myeloid leukemia (CML), Philadelphia-chromosome positive acute lymphoblastic leukemia and GIST.

The drug targets two proteins that have been linked with cancer. One of its targets is the C-Kit kinase, a protein that has been tied to gastrointestinal cancer, and another is Bcr-Abl kinase, a key protein controlling CML.

Not just for kicks, mind you, but to more specifically target one type of cancer while potentially curbing a rare life-threatening cardiotoxic side effect.

In a new study, it has been reported that the re-engineered Gleevec™ is just as effective as the original version against gastrointestinal stromal tumor (GIST) but carrying significantly less risk of heart failure.

Designed at Rice, using a new bottom-up approach for rational drug design (based on a rational strategy developed by Ariel Fernandez, professor of bioengineering), the re-engineered version of imatinib is now a new drug dubbed WBZ-4.

Said Ariel Fernandez:

“Our bottom-up design strategy is also broadly applicable to drugs other than imatinib and enables a rational control and reduction of side effects. For example, WBZ-4 was designed to target C-Kit without inhibiting the function of Bcr-Abl, which recent imatinib studies have associated with increased risk for heart failure.

We were successful in our three basic goals in redesigning the drug — we refocused the primary impact on C-Kit, we reduced the impact on Bcr-Abl, and we reduced cardiotoxicitity. Our results corroborate previous findings about the role that Bcr-Abl plays in the cardiotoxicity of imatinib.”

WBZ-4 is not yet available for human testing and dates for clinical trials have not been set.

But for sure, the endeavor will be pursued in the near future.

Find more details from Rice University.

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WBZ-4: Re-engineered Gleevec™, Reduces Cardio Risks

Now, according to a new research by a team from UC-Irvine, imatinib could cure CML under certain circumstances if it is taken over a long enough period of time.

According to mathematician Natalia Komarova and biologist Dominik Wodarz (respectively):

“There is evidence that a complete cure is possible. Several patients have been reported to have no symptoms after two months without therapy, which is thought to suggest a complete cure. This evidence supports our theory. Basically, one has to be on therapy long enough for all of the stem cells to wake up and be killed by the drug.

The model requires the number of cancer cells that exist, how fast the cells divide and die, and how fast they go to sleep and wake up. Once you have those numbers, you can determine how many drugs to use in combination to make sure drug resistant mutants do not become problems.”

Imatinib’s popular brand is Gleevec® – a product of Novartis Pharma.

The above findings appear Oct. 3 in the journal Public Library of Science (PLoS) One.

Find more details from UC-Irvine.

[Photo Credit: email wire]

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Imatinib Can Totally Cure Chronic Myeloid Leukemia

Preliminary data of a large, randomized, placebo-controlled clinical trial which tested imatinib mesylate (Gleevec ®) in patients with primary gastrointestinal stromal tumor (GIST) following complete removal of their tumor were found to be significantly less likely to have a recurrence of their cancer compared to the placebo group.

According to Elias A. Zerhouni, M.D., NIH Director:

“The standard treatment for primary GIST is complete surgical removal of the tumor without additional therapy. It is excellent news that addition of this well-tolerated cancer pill to the treatment regimen can have such a positive impact on decreasing the risk of recurrence.”

A product of Novartis Pharmaceuticals Corporation, Gleevec® belongs to a class of agents that block cellular communication to prevent tumor growth.

Gleevec®was USFDA-approved in 2002 for the treatment of unresectable or metastatic GIST.

The said clinical trial was sponsored by the National Cancer Institute (NCI) and conducted by a network of researchers led by the American College of Surgeons Oncology Group (ACOSOG).

Find more details from the full report.

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Cancer Drug Gleevec® Decreases Recurrence in Primary Gastrointestinal Stromal Tumor (GIST) Patients

The leukemia drug Gleevec, though hugely successful has some downsides too: heart failure in a few patients as shown in previous studies and now, drug resistance continues to be a problem.

Now, Kimmel Cancer Center at Thomas Jefferson University may have discovered a way to sidestep such resistance by reactivating a protein that is normally shut off in leukemia and in Gleevec-resistant cancer cells, leukemia development is halted.

A drug that could turn on the gene that makes the protein C/EBP-alpha, a “transcription factor” required for cells to differentiate, then, might control or even eliminate the cancer.

According to Bruno Calabretta, M.D., Ph.D., professor of cancer biology at Jefferson Medical College of Thomas Jefferson University:

Transcription factors are molecular switches that turn on genes when their function is needed. C/EBP-alpha expression is low in leukemia cells such as those with the BCR-ABL protein defect, which causes chronic myeloid leukemia (CML), a disease that Gleevec treats so well.

Gleevec is a novel cancer drug developed to fight cancer by turning off an enzyme that causes cells to become cancerous and multiply and is normally prescribed for patients early on in CML (characterized by an overabundance of white blood cells).

Read more details from the full report at EurekAlert.

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Jefferson Scientists Found Way that Might Sidestep Gleevec Resistance

A team of scientists led by Thomas Force, M.D., James C. Wilson Professor of Medicine at Jefferson Medical College of Thomas Jefferson University, has shown in studies in both mice and in heart cells in culture that Gleevec can cause heart failure.

“We found that the molecular target of the drug, the Abelson tyrosine kinase (ABL) protein, serves a maintenance function in cardiac muscle cells and is necessary for their health,” Dr. Force explains.

“While the cancer is treated effectively, there will be some percentage of patients who could experience significant left ventricular dysfunction and even heart failure from this.”

Gleevec, a new type of cancer drug, is the first of its kind developed to fight cancer by turning off an enzyme that causes cells to become cancerous and multiply.

The results of the above study conducted in 10 patients with chronic myelogenous leukemia (CML) who developed severe congestive heart failure while taking Gleevec, appeared July 23, 2006, in an advanced online edition of the journal Nature Medicine.

Read more at Thomas Jefferson University Hospital.

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‘Miracle’ Cancer Drug Gleevec May be Harmful to the Heart