By inhibiting a receptor on the surface of cancer cells, Tarceva and Iressa shut down the molecular signals inside lung cancer cells that tell them to grow and spread. Although dramatically successful at first, most tumors eventually develop resistance to the drugs and start growing again.
Now a study published Friday in the academic journal Science shows the battle against resistance may yet be won. An international research team led by investigators from Massachusetts General Hospital and the Dana-Farber Cancer Institute in Boston has discovered that the communication between cancer cells sometimes starts up again because of a gene called MET. MET tells cells to grow and divide even when Tarceva and Iressa are blocking the receptor they were designed to target.
Luckily for the 20 percent of resistant patients whose cases can be attributed to MET, lab tests combining MET inhibitors with Tarceva or Iressa appear to work. “We identified a potential new way to treat these resistant tumors with combination therapy directed against both protein targets,” said Pasi A. Janne, the study’s senior researcher.
Pharmaceutical companies developing MET inhibitors include the Quebec-based MethylGene, New York-based Pfizer, and California ’s Amgen and Exelixis. San Diego-based SGX is also developing a MET inhibitor. It is backed by the International Atlas Venture, New Leaf Venture Partners, and Biotechnology Value Fund.
Genentech spokesperson Krysta Pellegrino says it’s too early to tell how the findings might impact the sales of Tarceva. Approved by the FDA in 2004, San Francisco Bay Area-based Genentech has sunk over $200 million into research and development of the drug. Clinical trials continue to explore new indications, including phase III studies that combine Tarceva with Avastin, a drug that stops the blood flow and nutrient supply to tumors.
AstraZeneca’s Iressa, in the meantime, has struggled with its U.S. sales, which totaled only $3 million in the first quarter of 2007, compared with total global sales of $50 million. (Most of its success is in the East where Asian populations have proven more responsive.) FDA restrictions currently prevent Iressa from being prescribed to new patients.
“While MET inhibitors are in early development, they could potentially be combined with Iressa,” said Dr. Joseph Purvis, the executive director of Medical Science at AstraZeneca. “We have a number of clinical trials that will help us understand where [Iressa] will fit in to the U.S. and European markets.” |
