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Poet Richard Fox gains insight – and material – through cancer treatment
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Jeff's targeted therapy has kept his advanced lung cancer at bay.
When Pasi Jänne, MD, PhD, was a fellow, the Dana-Farber/Partners
clinical oncology fellowship suited him perfectly; it integrated
his two major interests, science and medicine, while introducing
him to distinguished mentors like Bruce Johnson, MD, of the Department of Medical Oncology. The
difficult part, he found, was having to tell patients that their
lung cancer had relapsed. Today, as a thoracic oncologist and
clinical researcher, Jänne is bringing new hope to patients by
uncovering the mechanisms of resistance in lung cancer and
designing more effective therapies.
The drugs gefitinib (Iressa) and erlotinib (Tarceva), which
inhibit the epidermal growth factor receptor (EGFR), initially work
in patients with EGFR mutations, but then fail as the tumors become
resistant to treatment. Studying exactly how this happens, however,
is no easy matter, explains Jänne, because patients do not
routinely undergo repeat biopsies that can be analyzed for genetic
To circumvent the problem, he and colleagues modeled resistance
in the laboratory, by treating EGFR-mutant cells with gefitinib and
isolating those that became resistant. Investigators then compared
the resistant cells to gefitinib-sensitive cells, deploying three
different techniques: genome-wide copy number analysis (using the
high-density SNP arrays adapted by Dana-Farber colleague Matthew
Meyerson, MD, PhD), RNA expression profiling and proteomic
analysis. "All three independent approaches pointed us in the same
direction," says Jänne, recalling the excitement of an entirely
unexpected discovery - amplification of the MET kinase gene, which
provided an alternate pathway for tumor growth.
Within a year, he had begun enrolling patients in a multicenter
clinical trial combining Tarceva with a MET inhibitor. "We were
hopeful of finding something new for patients," he says, "and we
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