Cancer "Wonder Drug" Still Effective Decades After Discovery—Are There Others Like It?

It’s been over twenty years since the FDA first approved Gleevec, the cancer drug hailed as a "miracle cure" due to its incredibly high success rates in treating chronic myelogenous leukemia, or CML, a rare cancer of the bone marrow.

Cancer "Wonder Drug" Still Effective Decades After Discovery—Are There Others Like It?
The Oregon Health & Science University’s Knight Cancer Institute is home to Dr. Druker’s groundbreaking research into targeted cancer therapy.

For Gleevec, being a cancer wonder drug wasn't just a phase.

It's been over twenty years since the FDA first approved Gleevec, the cancer drug hailed as a "miracle cure" due to its incredibly high success rates in treating chronic myelogenous leukemia, or CML, a rare cancer of the bone marrow.

Only two treatments existed for CML at the time Gleevec was introduced. The first was a bone marrow transplant, a complicated operation with severe risks of side effects. The second involved daily interferon infusions utilizing the only available drug for this type of leukemia.

Before 2001, patients with CML had a five-year survival rate of 30%, but after Gleevec was introduced, that number dramatically climbed closer to a whopping 90% — a seemingly miraculous difference.

However, Gleevec has had even more of an impact than that. Besides saving lives by vastly improving health outcomes for patients with CML, Gleevec also ushered in a new era of targeted cancer therapy, changing the field of cancer research forever.

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A New Approach

Dr. Brian Druker, director of the Knight Cancer Institute at Oregon Health & Science University (OHSU), is one of the scientists who discovered Gleevec. In a 2009 interview with the New York Times, he discussed the underlying ideology that initially led him to discover imatinib mesylate, the scientific name for Gleevec.

As an oncologist during the 70s and 80s, he recalls his frustration with the chemotherapeutic practices of the time, referring to them as the "baseball bat" method. Basically, this meant trying to cure cancer by overpowering it. Dr. Druker was one of the first oncologists to adopt a different approach. To stop the spread of cancer cells, he first tried to understand their biology and worked to develop drugs to address that, pioneering the era of targeted cancer treatment.

Instead of just trying to kill every nearby cell in an attempt to obliterate cancer, Gleevec was the first drug of its kind that specifically targeted cancerous cells, leaving healthy cells undamaged. This dramatically improved the prognosis of patients with CML and also changed cancer research by heralding new tyrosine kinase inhibitor (TKI) medications.

Decades in the Making

Gleevec was discovered in the 90s by biochemist Nicholas Lydon and oncologist Brian Druker while they were working at Ciba-Geigy, known today as the pharmaceutical giant Novartis.

By 2003, the drug's efficacy had become so evident that its explosive popularity was chronicled in Dr. Daniel Vasella's 2003 book Magic Cancer Bullet: How a Tiny Orange Pill May Rewrite Medical History. Still, like most scientific discoveries, the foundation of the "miracle drug" had already been laid decades earlier.

The Philadelphia Chromosome

Scientists Peter Nowell and David Hungerford first discovered a unique irregularity in the chromosomes of patients with CML in the 1960s. Since scientists had previously been unable to link a specific abnormality to a particular cancer, this marked a breakthrough in research. They called it the "Philadelphia Chromosome."

In the following decades, more studies on the Philadelphia Chromosome discovered a fusion gene called BCR-ABL, which produced an overactive tyrosine kinase enzyme that propels the uncontrolled growth of leukemic cells in CML patients.

STI571: Too Good To Be True

The discovery of BCR-ABL opened the door for a new, targeted therapy approach. Instead of trying to kill mature cancer cells, researchers began trying to see if they could inhibit the overactive tyrosine kinase enzyme, dawning the era of tyrosine kinase inhibitors (TKIs).

The duo of Dr. Lydon and Druker started working on compounds that would act as TKIs, directly affecting the growth of cancer cells. Dr. Lydon created the compound STI571, and Dr. Druker identified it as being exceptionally effective against cancer cells in CML. Before long, Gleevec was on the path to clinical development. At the time, STI571's high success rates were considered miraculous—or impossible—depending on who you spoke to, and Dr Druker recalls early skeptics thinking the results were "too good to be true" and that he was a charlatan.

Clinical Trials and Approval

However, early skepticism quickly died down. Findings from STI571's first clinical trials, which started in 1998, were nothing short of astonishing. The unprecedented high success rate earned STI571—now named Gleevec—the name "wonder drug" as the oral medication rapidly moved through clinical trial phases. The FDA approved Gleevec for commercial use in 2001.

Enduring Effectiveness

A follow-up study five years later revealed that the breakthrough treatment had passed the first hurdle with flying colors. After 60 months of Gleevec therapy, Druker's team found that 98% of patients had shown a positive or complete hematologic response. Additionally, the estimated overall survival rate after five years had jumped from 30% to 89%.

In 2017, a second follow-up review was published, this time by the New England Journal of Medicine. The comprehensive study was conducted in 16 counties, involving 1106 participants at 177 cancer centers. Although there was a slight dip in the survival rate—a common occurrence after a medication has been around for a while—results showed that ten years after diagnosis, CML patients who had received Gleevec treatment had an estimated survival rate of 83.3%. This once more confirmed the remarkable long-term efficacy of the drug.

Paving the way

Gleevec's legacy and its impact on cancer research continue to inspire the development of new treatments, marking a new era of precision medicine. Researchers alongside Dr. Druker at OHSU have continued to push the boundaries of what's possible in the field as they work to understand the mechanisms that drive cancer growth. In fact, Gleevec has already yielded promising results for numerous other cancers, including gastrointestinal stromal tumors (GIST).

Are there more wonder drugs like Gleevec (what does the future hold for cancer research)?

It might be too early to tell, but scientists are hopeful.

Dr. Daniel Longo, a Harvard Medical School professor, echoes these sentiments by hailing Gleevec as having "fundamentally altered the field of oncology." As scientists' priorities shift from focusing on cancer cell division to understanding cancer biology, the door is open for similar targeted therapies to emerge.

Now, as researchers better understand the individual makeup of various cancers, other wonder drugs may soon be discovered, showing a lot of hope and promise for the future of cancer research.

Studypages’ Collaboration with OHSU’s Knight Cancer Institute

Dr. Druker’s revolutionary research in targeted cancer therapy finds its epicenter at the Oregon Health & Science University’s (OHSU) Knight Cancer Institute. In our ongoing commitment to eliminate silos in research and democratize research accessibility, Studypages proudly partnered with OHSU’s Knight Cancer Institute to unveil a dedicated Studypages Gallery focused on cancer-specific studies. Discover the OHSU Knight Cancer Gallery here.

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