用Fluidigm digital array芯片研究癌细胞
Technology
Review网站在2009年9月30日发表了题为《Analyzing Cancer Cells to Choose Treatments——
Microfluidics chips allow scientists to study circulating cancer cells
and determine their vulnerabilities》的技术文章,详细介绍了美国Fluidigm公司的微液流芯片Digital
Array在癌细胞研究中的应用。详细内容为:
Analyzing Cancer Cells to Choose Treatments
In
a new clinical trial for prostate cancer, scientists will capture rare
tumor cells circulating in patients' blood, analyze them using a
specialized microchip, and use the results to try to predict how well
the patient will respond to a drug. The trial reflects a new phase of
personalized medicine for cancer, enabled by microfluidics technologies
that can isolate scarce cancer cells and detect very small changes in
gene expression. Physicians ultimately hope these chips can become a
routine part of clinical care for cancer. "We need to be able to profile
the tumor at the time we are considering treatment," says Howard Scher,
chief of the Genitourinary Oncology Service at Memorial Sloan-Kettering
Cancer Center, where the trial will take place.
The study will
focus on men with a difficult to treat form of prostate cancer that has
failed to respond to other therapies. Changes in gene expression might
help determine whether a specific drug will be effective--for example,
if a patient has high levels of a receptor for androgen hormones, a drug
that inhibits signaling of that receptor is more likely to work well.
"We want to know why they don't respond to therapy and what therapies
would be best for them," says Martin Fleisher,
chairman of the Department of Clinical Laboratories at Sloan. "We
collect tumor cells from blood, and do a gene analysis to find out what
genes are overexpressed and whether or not they would be candidates for
certain types of targeted therapies that would beat down their cancer."
The effectiveness of different cancer drugs can vary based on the
molecular characteristics of the cancer, such as the presence of a
certain hormone or genetic mutation. Physicians already do some
molecular analysis of cancer tissue to select the best drug for a
patient. Herceptin, for example, is used to treat breast cancer in women
with a particular protein in their tumors. And lung cancer patients
with a mutation in the gene for the epidermal growth factor receptor are
more likely to respond to a drug called Iressa than patients without
it. But these treatments are chosen based on analysis from tumor
biopsies, which isn't always possible.
Analyzing tumor cells in
blood presents two major challenges. Tumor cells are found at very low
concentrations in the blood--about one in ten million cells--making it
difficult to isolate them. And the small numbers of cells must be
analyzed in very low volumes. In the last year, Sloan scientists and
others have developed ways to capture these cells using antibodies that detect a molecular marker present only in cancer cells.
In the new Sloan study, scientists face an even more challenging
problem--they must detect differences in gene expression, rather than a
specific genetic mutation, such as the mutation linked to Iressa
responsiveness in lung cancer. Scher and collaborators will use a
microfluidics chip made by Fluidigm,
a South San Francisco, CA- based company . DNA from each cell is
filtered into one of 96 tiny channels on one side of the chip, while
reagents flow in from 96 channels on the other side. A precise plumbing
system then combines the molecules in different combinations, generating
about 9,000 simultaneous reactions. Each reaction takes a volume of
just nanoliters--about the size of a period--rather than the microliter
volume typical of most commercial fluidics devices. The chip, which
costs about $300, "can detect differences in gene expression that are as
subtle as twofold with very good accuracy," says Gajus Worthington,
Fluidigm's president, CEO, and co-founder.
Researchers plan to
analyze levels of about 30 genes in each patient, including genes
involved in production of testosterone and in cell signaling. Expression
of these genes has been shown in animal models to predict how well a
tumor will respond to a drug called dasatinib, which is approved for
treatment of chronic myelogenous leukemia and in late stage clinical trials for prostate cancer.
The microfluidics technology could also be used to examine other properties of tumor cells. Scientists might look for changes in gene expression that suggest a cancer has metastasized, or whether a tumor has evolved specific mutations that make it resistant to specific drugs