RISE Alum Returns to Share his Journey in the Development of a Cancer Drug

by Katelynn Fleming

The RISE program has allowed students to work with accomplished researchers since 1979. Dr. Louis Lombardo was a part of the RISE program at its inception, working with a RISE fellow on lab-based research while earning his B.A. in Biochemistry. He went on to graduate studies at Yale University and emerged with a Ph.D. in Synthetic Organic Chemistry. Last Wednesday, Lombardo returned to share a case study and a bit of wisdom with the Drew community.

Lombardo shared his experiences in drug development at Bristol-Myers Squibb where he was part of the research team for the cancer drug Sprycel (generic name Dasatinib), which has been approved and on the market since 2006 to treat chronic myeloid leukemia (CML). CML is spurred by a mutant gene that causes a protein, Bcr-Abl, to malfunction. The drug Gleevec (generic name Imatinib) was the only drug that could inhibit the protein before Sprycel was developed, but a multitude of mutations built resistance to the drug causing it to stop working after a time.

Cue Sprycel, the prize at the end of a long drug discovery process. It was discovered not by oncologists (cancer researchers) but by immunologists looking for something totally different. When screening compounds for their drug target, they noted that the compound inhibited proteins in the same family as Bcr-Abl and passed it on to their colleagues in Bristol-Myers’ oncology group. The oncology group agreed and went through a long and arduous process to optimize the chemical structure and increase its potency. Lombardo joined on the project as the drug began to go into in-vivo trials. Researchers found that the drug was very effective in small doses and did not become toxic until a dose about ten times as high. It also successfully inhibited the growth of CML cells, even in Gleevec-resistant cells. Lombardo emphasized that this early success is very unusual and added, “There’s a lot of luck here. Everything lined up just right.” The drug then went through very successful clinical trials in patients with different progressions of the disease and was approved as a drug for Gleevec-resistant patients in 2006. After four more years of trials in patients who had not had Gleevec, Sprycel was finally released in 2010 as a first-line treatment for patients with CML. To tie up the presentation, he showed a blog post from a patient who was filled with hope, joy and thanks at the success of the new drug and the impact it would have on people with CML. Dr. Lombardo remarked, “That’s why we do it.”

At the end of his presentation, Dr. Lombardo answered questions from the audience, many of whom were current RISE fellows. He shared his takeaways from the presentation about drug discovery, as well as a favorite quotation by Louis Pasteur, “Chance favors the prepared mind.” His message was that you never know exactly what you will get in research and life, so keeping your eyes open can lead to huge discoveries that you never could have predicted.

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