The Trials and Tribulations of a Revolutionary Cancer Drug 

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A modest brass plaque above a booth in the Eagle Pub in Cambridge, notes, “On this spot, on February 28, 1953, Francis Crick and James Watson declared the discovery of DNA with these words: ‘We have discoverewd the secret of life.’” Announcing a major scientific advance over a pint of ale is a far cry from the standing-room-only crowd at the 2006 ASCO Annual Meeting, where Brian Drucker, MD, presented data from the 5-year follow-up of patients taking imatinib (Gleevec) for chronic myeloid leukemia (CML). It wasn’t the secret of life, but the development of imatinib revolutionized the treatment of CML.

A diagnosis of CML was once a death sentence. These days, if CML is diagnosed early, it can be managed as a chronic disease, giving patients many years of good-quality life. The deadly leukemic cells these patients harbor in their bone marrow are kept corralled by the tyrosine kinase inhibitor drug imatinib. And it almost didn’t happen.

Early on, CML was thought to be too uncommon to justify the huge investments in research, development, and regulatory costs needed to bring it to market. Obviously, the visionaries won out over the bean counters. And that story, in a nutshell, is the basis of Jessica Wapner’s new book, The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level.

Tall Order

The audience for this type of science-based book is generally known as the “smart lay public.” The allure of science books depends on intellectual nourishment served in a compelling narrative, which is a tall order. The challenge for the author is to walk a delicate information line—giving just enough science to nourish readers with knowledge while keeping the book rolling along without a surfeit of facts and theory bogging down the pace.

The Philadelphia Chromosome has an added challenge as the author charts the discovery of the gene that led to the development of imatinib: There are no zany characters, exciting locales, or juicy anecdotes. Even the hero, Dr. Drucker, is painted in the most neutral of colors, leaving the reader wanting a tad more.

These limitations don’t make for a bad book; they just narrow the potential readership down to those who are thrilled by a story that Robert A. Weinberg, PhD, describes in the forward thusly: “The story that this book relates vindicates those who dreamed that one day cancers could be treated through rationally designed drugs—and in fact remains the major success story to this day…. This book makes good reading for those interested in the work of the heroes who pushed this drug forward to its truly brilliant successes.”

Jessica Wapner is a sturdy writer who has good command of a difficult subject. The book has been well researched and benefits from first-hand accounts of more than 35 interviews. This can be heady content, and Ms. Wapner is at her best when she sharpens her descriptions of biology and oncology so the layperson can be challenged but not overwhelmed.

For example, here she teaches something in plain language: “Finding a way to turn a compound into a drug that would not be immediately rejected or disintegrated by the body would not be easy. To enter the body, the molecule had to be stable in water without dissolving. To leave the body, the drug, having done its work, had to penetrate the portal vein, which goes through the liver, where the remnants could be broken down for excretion.”

Her sections on tyrosine kinase inhibitors, however, risk overload, and many of those passages become overwhelming.

Select Audience

Readers of The ASCO Post will appreciate the step-by-step process that produced one of modern oncology’s greatest success stories. Some of the most compelling sections deal with the battle to get the drug into the pipeline. In those parts, the true heroes of this tale emerge as champions for patients with cancer. But be prepared, years drag by before imatinib finally receives FDA approval.

In that regard, The Philadelphia Chromosome also leaves us wanting more. At the book’s close, Dr. Drucker said of his hope for the future, “There would be a Gleevec for every cancer.… [I]t’s all about target. Identifying the right target, getting a good drug to market, and not worrying about [the size of the market].”

The Philadelphia Chromosome can be a challenging read at times, but for a select audience, it is worth the effort. ■