Daniel A. Haber, M.D., Ph.D.
Massachusetts General Hospital Cancer Center
Boston, MA
NFCR Project Director

Targeting genetic lesions in human cancer

Dr. Daniel Haber’s work is mainly focused on identifying genetic abnormalities in tumors, with the goal of finding “vulnerabilities” within the tumor that may render it susceptible to therapeutic agents. One of his most noteworthy research breakthroughs is his finding that mutations in a growth factor receptor (EGFR) predict which lung cancers are likely to have dramatic responses to drugs such as Iressa™ that specifically attack the receptor.

The puzzle of Iressa

Iressa™ is a drug that specifically targets the protein Epidermal Growth Factor Receptor (EGFR) which is overly expressed in many types of cancer cells, including non-small cell lung cancer (NSCLC). However, only 13% of NSCLC patients see their tumor shrink after treatment with Iressa, while the other 87% do not. What makes the 13% of patients respond well to the drug? How can we screen for this small group of patients? These questions must be answered prior to the start of treatment procedures.

Tailoring Iressa to the right patients

Searching for answers to these questions, Dr. Haber discovered that only patients with a mutant or malfunctioning EGFR protein in their cancer cells respond well to Iressa. This critical finding makes it possible to identify the 13% of patients who can potentially benefit from Iressa. Dr. Haber’s research provided important guidance for oncologists and assures that lung cancer patients receive the most beneficial therapy available from the onset of treatment.

The malfunctioning EGFR protein is caused by the mutation in its DNA, the EGFR gene. By running genetic tests on this particular gene in NSCLC patients, doctors can now predict whose tumor is likely to respond well to Iressa. For those whose gene profile indicates that Iressa is unlikely to work, other available treatments can be initiated. This may make the difference between life and death for many NSCLC patients.

This breakthrough discovery not only helps to tailor Iressa to the right cancer patients, it also has profound indication in guiding the usage of other drugs, such as Tarceva™, which also works by blocking EGFR.

Identifying genetic lesions in other types of cancer

In addition, Dr. Haber’s research team has expanded their work on identifying genetic lesions in other types of cancer, including breast, gastric, esophageal, and head and neck cancer. The team has already identified several important genetic mutations in those cancers, and again, these findings may provide crucial guidance for oncologists to treat cancer patients in a more tailored, more effective way.

Recent Breakthrough – tracking cancer in real-time

Dr. Haber’s research team recently designed a new cutting-edge microchip-based device called the CTC-chip, which can pick up very rare cancer cells that have entered the blood from their originating organs such as the lungs.

By running a spoonful of blood through the business-card-size CTC-chip, very rare circulating tumor cells (CTCs) can be trapped onto the chip and isolated. Dr. Haber’s research has shown that the change in the amount of CTCs in the blood correlates well with treatment effectiveness. Moreover, the CTC-chip technology allows continuous monitoring of tumor cells’ genetic makeup, which could change during treatment. According to a clinical trial in patients with non-small cell lung cancer, new genetic mutations could appear within 3 to 4 months following initial treatment, causing tumor resistance to the current therapy. Continuous tracking such genetic changes in individual patients is essential for doctors to make timely treatment adjustment, but it is almost unthinkable if this has to be done through repeated, painful, and invasive tumor biopsy. The CTC-chip offers a very practical alternative through non-invasive blood testing, which is almost as accurate as tumor biopsy (92% of effectiveness). Dr. Haber is currently optimizing the CTC-chip for large scale clinical application, and his breakthrough technology may soon reach patients’ bedside, changing the face of clinical cancer care.


Dr. Haber’s research breakthrough on lung cancer treatment and his continuing efforts in deciphering the genetic puzzles of other types of cancer will greatly accelerate the development of targeted cancer therapies and personalized medicine. NFCR has been supporting Dr. Haber’s research since 2004.