Test could lead to better cancer treatment
By Stephen Smith, Globe Staff
Boston researchers have developed a test that can identify minute amounts of tumor cells floating in the blood of cancer patients, a discovery that could lead to better treatments with fewer side effects.
The technology invented at Massachusetts General Hospital uses a microchip scanner no bigger than a business card to analyze a patient's blood, hunting for stray cells shed by tumors. The device is so powerful that it can sniff out a single cancer cell among 1 billion healthy blood cells.
Once those cells are captured, their genetic fingerprints can help determine the most effective drug for a patient whose cancer has already begun spreading, and also show whether medication has lost its effectiveness. Now, the technology is used in patients whose cancer has already spread, but scientists hope in the future the chip will be able to detect cancer's spread before secondary tumors have become established.
Although the device is not yet ready for widespread use, a report posted online today in the New England Journal of Medicine showed that it successfully identified migrating cancer cells in lung cancer patients and spotted important genetic quirks in those cells.
Scientists not involved with the research said the innovation represents a significant improvement on existing cancer blood tests and predicted that it could revolutionize treatment, especially for lung cancer, which kills more Americans than any other cancer.
Mass. General's approach brings together two of the hottest fields in cancer research: the incredibly tiny devices of nanotechnology, and personalized medicine, the promise of tailoring treatments to individual patients.
"To me, as a scientist, this is huge," said Dr. Shakun Malik, director of the lung cancer program at Georgetown University's Lombardi Comprehensive Cancer Center in Washington, DC. "To be able to just do a blood test, that opens a whole new, wide world. It will give us a lead time to find out if the patient has stopped responding to treatment."
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Elizabeth Cooney is a former
health reporter for the Worcester Telegram & Gazette, where she also was a
business reporter and an editor. Earlier in her career, she edited medical
books and journals at Little, Brown, and worked for Boston magazine.Boston Globe Health and Science staff:
- Gideon Gil, Health and Science Editor
- Ishani Ganguli, Short White Coat blogger
Nice good blog!
Personalized Cancer Medicine Is Here, Now!
As we enter the era of "personalized" medicine, it is time to take a fresh look at how we evaluate treatments for cancer patients. More emphasis is needed matching treatment to the patient. Patients would certainly have a better chance of success had their cancer been chemo-sensitive rather than chemo-resistant, where it is more apparent that chemotherapy improves the survival of patients, and where identifying the most effective chemotherapy would be more likely to improve survival.
Findings presented at the Annual Meeting of the European Society for Clinical Investigation in Uppsala, Sweden and the Annual Meeting of the American Assoication for Cancer Research (AACR) in San Diego, CA concluded that "functional profiling" with cell-based assays is relevant for the study of both "conventional" and "targeted" anti-neoplastic drug agents (anti-tumor and anti-angiogenic activity) in primary cultures of "fresh" human tumors.
Cell-based Assays with "cell-death" endpoints can show disease-specific drug activity, are useful clinical and research tools for "conventional" and "targeted" drugs, and provide unique information complementary to that provided by "molecular" tests. There have been more than 25 peer-reviewed publications showing significant correlations between cell-death assay results and patient response and survival.
Many patients are treated not only with a "targeted" therapy drug like Tarceva, Avastin, or Iressa, but with a combination of chemotherapy drugs. Therefore, existing DNA or RNA sequences or expression of individual proteins often examine only one compenent of a much larger, interactive process. The oncologist might need to administer several chemotherapy drugs at varying doses because tumor cells express survival factors with a wide degree of individual cell variability.
There is a tactic of using biopsied cells to predict which cancer treatments will work best for the patient, by taking pieces of live "fresh" tumor tissue, applying different chemotherapy treatments to it, and examining the results to see which drug or combination of drugs does the best job killing the tumor cells. A cell-based assay test with "functional profiling," using a cell-death endpoint, can help see what treatments will not have the best opportunity of being successful (resistant) and identify drugs that have the best opportunity of being successful (sensitive).
Funtional profiling measures the response of the tumor cells to drug exposure. Following this exposure, they measure both cell metabolism and cell morphology. The integrated effect of the drugs on the whole cell, resulting in a cellular response to the drug, measuring the interaction of the entire genome. No matter which genes are being affected, functional profiling is measuring them through the surrogate of measuring if the cell is alive or dead.
For example, the epidermal growth factor receptor (EGFR) is a protein on the surface of a cell. EGFR-inhibiting drugs certainly do target specific genes, but even knowing what genes the drugs target doesn't tell you the whole story. Both Iressa and Tarceva target EGFR protein-tyrosine kinases. But all the EGFR mutation or amplificaton studies can tell us is whether or not the cells are potentially susceptible to this mechanism of attack. They don't tell you if Iressa is better or worse than Tarceva or other drugs which may target this. There are differences. The drugs have to get inside the cells in order to target anything. So, in different tumors, either Iressa or Tarceva might get in better or worse than the other. And the drugs may also be inactivated at different rates, also contributing to sensitivity versus resistance.
As an example of this testing, researchers have tested how well a pancreatic cancer patient can be treated successfully with a combination of drugs commonly used to fight lung, pancreatic, breast, and colorectal cancers. The pre-test can report prospectively to a physician specifically which chemotherapy agent would benefit a cancer patient. Drug sensitivity profiles differ significantly among cancer patients even when diagnosed with the same cancer.
The funtional profiling technique makes the statistically significant association between prospectively reported test results and patient survival. It can correlate test results that are obtained in the lab and reported to physicians prior to patient treatment, with significantly longer or shorter overall patient survival depending upon whether the drug was found to be effective or ineffective at killing the patient's tumor cells in the laboratory.
This could help solve the problem of knowing which patients can tolerate costly new treatments and their harmful side effects. These "smart" drugs are a really exciting element of cancer medicine, but do not work for everyone, and a pre-test to determine the efficacy of these drugs in a patient could be the first crucial step in personalizing treatment to the individual.
Literature Citation:
Functional profiling with cell culture-based assays for kinase and anti-angiogenic agents Eur J Clin Invest 37 (suppl. 1):60, 2007
Functional Profiling of Human Tumors in Primary Culture: A Platform for Drug Discovery and Therapy Selection (AACR: Apr 2008-AB-1546)
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