The Evolution of a Lifesaving Drug: A Scientist Reflects

Pictured: Charles Sawyers

Physician-scientist Charles Sawyers

Starting in the mid-1990s, while he was at the University of California, Los Angeles, Memorial Sloan Kettering physician-scientist Charles Sawyers played a pivotal role in the development of imatinib (Gleevec®), one of the first successful targeted drugs for cancer. Gleevec was originally developed for the treatment of chronic myeloid leukemia (CML) and is now used to treat a number of cancer types.

Dr. Sawyers joined MSK in 2006 as the inaugural Chair of our Human Oncology and Pathogenesis Program. His laboratory focuses on developing new targeted therapies for advanced prostate cancer and leukemia.

We asked Dr. Sawyers about the moment he knew that Gleevec was going to be a game changer in the treatment of CML.

When I was in medical school, I became captivated by the potential advances that molecular biology could bring to medicine, especially cancer medicine. At that time in the early 1980s, there weren’t many concrete examples of what was possible, but to me it seemed like the next great thing.

During my medical internship, I was greatly affected by the time I served on the leukemia ward.

I became captivated by the potential advances that molecular biology could bring to medicine.
Charles Sawyers MSK physician-scientist

It was the first time I took care of patients my age. Leukemia treatment was very intensive. Patients spent a month in the hospital, and you got to know them well. Based on that experience, I decided to focus on leukemia research.

In 1996, I became involved in the initial testing of a drug for the treatment of CML, which eventually was named Gleevec. CML is unique in that it is caused by a single mutant protein, called BCR-ABL.

Gleevec is a pill taken once a day with few side effects. It worked so well so early in the trial that it was obvious to all of us involved that it had to be moved forward as quickly as possible. The clinical impact was so dramatic that we became evangelists, trying to get the resources to speed up the clinical testing. Not only did we see almost instant improvement in patients with early-stage CML, we also saw dramatic results in patients who were in blast crisis, the most advanced stage of the disease.

I’ll never forget it. Some of these patients were hospitalized, in wheelchairs, and on oxygen with only weeks or months to live. Within a week or two, they were walking out of the hospital in complete remission.

But the sad part was that these sicker patients who underwent the most dramatic recoveries were the first to develop resistance to the drug, and they relapsed quickly. We set out to solve the puzzle of why patients were developing resistance, which is really the Achilles’ heel of targeted therapy.

The clinical impact was so dramatic that we became evangelists.
Charles Sawyers

We learned that in most patients, an additional mutation was occurring in the BCR-ABL protein, causing it to change its shape and preventing the drug from working. Soon after that we got a call about another drug — which became known as dasatinib (Sprycel®) — that inhibited BCR-ABL in its other shape.

Clinical trials with dasatinib began very quickly, but this time we changed the way we conducted them. We did genetic studies on every patient to give us additional insight into what mutations each patient had. Today when we treat CML, we can use these gene-based measurements to instruct us about which drug to use and to predict how each patient will do.

This genetic analysis of patients’ tumors has become a part of standard care for MSK patients with many different types of cancer. It helps guide the development of new therapies and is the cornerstone for what’s now being called precision medicine.

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How to treat remaining SQUAMOS CELL CARCINOMA once primary is found.

Dear Richard, here is an overview on the treatment of squamous cell carcinoma from our website:

You may also be interested in reading more on the National Cancer Institute’s site:

If you or a loved one would like to make an appointment for a consultation with one of our physicians, please call our Physician Referral Service at 800-525-2225.

Thank you for your comment.

Is there any success documented on using proton therapy for large B cell lymphoma in the neck this is wrapped around the jugular vein and the carotid artery.

Thanks so much for your question. We reached out to proton therapy expert Oren Cahlon. He writes: “Proton therapy can be considered in some select cases of large cell lymphoma. I would encourage the patient to discuss this with their doctors to see if it is appropriate for this particular case.” Thanks again for reaching out.

Dr. Charles Sawyers. I want to thank you from the bottom of my heart for discovering targeted therapy for CML. I was diagnosed at age 61', this past February,2015. I am feeling fine,and my outlook for life is that I will live another 30 years. I have moved on from Gleevec to Tasigna, and feel like I have not one health related illness. The words Thank YOU seem so insignificant, yet I don't know what else to say. God Bless you every day. A very happy and healthy patient.Marie

Thank you for your kind words! We will share them with Dr. Sawyers. We’re so glad to hear you’re doing well!

Does Dr. Sawyer have any clinical trials targeting ATM gene which I believe is common in Leukemia?

Dear Adam, we currently have a clinical trial investigating a drug that blocks ATM in people with advanced solid tumors:

To browse through our clinical trials for people with leukemia, please visit:…

If you have questions about any of our clinical trials, please call our Physician Referral Service at 800-525-2225. Thank you for reaching out to us.

Dr. Sawyers,

My 92 year old Father was diagnosed in May (after a fall) with stage 4 prostate cancer. He began a regimen of taking XTANDI the drug you helped to develop and his PSA came down dramatically after 4 weeks. He also received one injection of another drug after 6 weeks, my Dad began having problems in swallowing the large 40 mg pills. Three have since gotten Stu k in his throat, opened and started to burn his esophagus.

He has been off the pills for over a month.

They did a barium swallow test and are now recommending that he have an endoscopy to stretch his esophagus.

He is so worried that he may have a stroke or die during the procedure.

He has a pacemaker and is on warfarin which they will stop

I called the drug company a nd they do t make the pills any smaller.

Do you have any advice or suggestions? I wish we could have someone make him special pills. I k ow that would be 8 a day vs 4 but my Mom and I don’t want him to die just to be able to take the pills

Would there be any other options?

Thank you.

A concerned and loving daughter.

Dear Susan, we’re sorry to hear your father is going through this. We recommend that you discuss your concerns with his medical team. Thank you for your comment, and best wishes to you and your family.