Massachusetts General Hospital Cancer Center
Boston, MA
NFCR Project Director

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^TM that specifically attack the receptor.

The puzzle of Iressa

Iressa^TM 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^TM, 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.Dr. Haber and his team are using state-of-the-art technologies to identify all of the cancer-causing abnormalities in pediatric and adult tumors, and again, these findings guide oncologists in the selection of targeted therapeutics that match these genetic vulnerabilities. This trailblazing approach will provide patients with a more tailored, more effective cancer care.

Recent Breakthrough - Recent Breakthrough - The CTC-Chip - that is dramatically changing the way cancer is detected and treated

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.

CTC Chip for Treatment of Cancer Cell Invasion (Early Metastasis)

Researchers believe the genes that make healthy cells migrate and become new tissues during normal embryonic development may also contribute to abnormal processes used by cancer cells to invade nearby healthy tissue. This first step of invasion enables cancer cells to migrate through tissues, reach a blood vessel, circulate through the bloodstream as rare CTCs, and may eventually grow into a deadly tumor at a distant site in the body through metastasis. From gene libraries, Dr. Haber is defining a key set of candidate genes for normal and abnormal migration. Next, CTCs collected on the Chip from blood samples of metastatic breast cancer patients will be analyzed for activities of the candidate genes for cancer migration and invasion. His innovative research plan may identify novel molecules that can serve as either biomarkers of cancer cell invasion or as targets for development of therapeutic agents that will stop the early steps in cancer metastasis and prevent cancer cells' lethal migration and metastasis to distant sites.

Impact on Cancer Prevention, Early Diagnosis, or Treatment

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. The CTC chip is now being optimized for large scale clinical application. This breakthrough technology may soon reach patients' bedside, dramatically changing the face of clinical cancer care. NFCR has been supporting Dr. Haber's research since 2004.