Gene Chip Enables Personalized Cancer Treatment
Tuesday, October 23, 2007 - Einat Rotman
Home >> News >> Cancer Research
An oncologist from Michigan has devised a new approach to clinical medicine. Using DNA micro-array chips, Dr. Eric Lester analyzed gene expression profiles of tumors in patients with advanced incurable cancer. For each patient, he first identified certain genes associated with a favorable response to anti-cancer drugs, and then determined an individualized treatment plan according to these findings.
Dr. Eric Lester, of the Oncology Care Associates in St. Joseph, Michigan, devised an experiment that illustrates the promise of personalized medicine. He had six patients with advanced, incurable cancer. In order to determine which anti-cancer drugs would benefit each patient, Lester analyzed his patients' tumors, seeking the expression of genes associated with responsiveness to various anti-cancer drugs. He then based his drug treatment plans on the experiment's findings.
To analyze gene expression in the tumors Dr. Lester used Affymetrix's DNA micro-arrays, which are small chips used to measure genetic information on a large scale. Affymetrix's gene chips can be tagged with hundreds of thousands of gene sequences that will either attract or repel pieces of DNA or RNA from a certain sample. The attraction or repulsion of the DNA and RNA indicate gene mutations (genotype testing) or gene activity patterns (expression testing) in the sample. †
Dr. Lester and Craig Webb, Ph.D., Director of Translational Medicine at the Van Andel Research Institute in Grand Rapids, Michigan, surveyed the scientific literature and compiled a list of genes whose expression levels may predict responsiveness to certain drugs against a type of tumors. Webb and Lester compared the tested patients' personal micro-array results to the pharmaceutical and genomic data bases and determined an individualized treatment plan for each patient. More information on Lester's study can be found on the Van Andel Research Institute website and on the American Association for Cancer Research website. In some cases, after analyzing the information derived from the chips, the doctors suggested completely different treatment strategies for patients with the same type of cancer. TFOT recently covered a couple of other research projects dealing with chips for detection of cancer biomarkers. These chips include the "lab on a chip" device enabling detection of oral cancer cells, developed at the Texas University, and the Nanocytometer, which locates cancer cells or other specific cells in the blood, developed at the University of California, Berkeley. Further discussion of personalized gene-chip based treatment can be found in the TFOT forums.
TFOT recently covered a couple of other research projects dealing with chips for detection of cancer biomarkers. These chips include the "lab on a chip" device enabling detection of oral cancer cells, developed at the Texas University, and the Nanocytometer, which locates cancer cells or other specific cells in the blood, developed at the University of California, Berkeley.
Further discussion of personalized gene-chip based treatment can be found in the TFOT forums.
|Related Pictures||Purple Tomatoes to Fight Cancer||New Contrast Agent to Help Fight Cancer|
|Other Articles||Mempile - Terabyte on a CD||Cybook Gen3 e-Book Review|
This years winner of the Otto Warburg prize, Robt A Weinberg, switches
on 3 genes in human cell types and causes cancer. He switches the
gene for telomerase, turns off a tumor suppressor gene, and turns on
an oncogene. Telomerase alone switches another 217 genes to cancer
mode (Elizabeth Blackburn) and starts glycolysis (Mohammed
Kashani-Sabet). The "Greene Chip" being tested now by the CDC and the
W.H.O., detects dna fragments of over 30,000 human pathogens. The
Greene Chip must be made to include Weinbergs 3 genes!
I assume there can be a lot of sets of genes that can cause cancer.
The three you mentioned are just one example of such a set
Microarrays (gene chips) examine what genes are expressed in cancer
cells. It is mainly used for screening/gene discovery work. You screen
50,000 genes to discover an association and then you focus in on only
a few hundred or so for more careful study by some other method like
real time polymerase chain reaction (RT-PCR).
Genes make proteins, the molecules that comprise and maintain all the
body's tissues. Genes produce their effect by sending molecules called
messenger RNA to the protein-making machinery of a cell. They set the
protein-making machinery in motion through a "gofer" messenger called
RNA (or mRNA).
The technique called RNA interference (RNA-i) allows scientists to
"silence" certain genes. In RNA interference, certain molecules
trigger the destruction of RNA from a particular gene, so that no
protein is produced. Thus, the gene is effectively silenced. RNA
interference is already being widely used in basic science as a method
to study the function of genes and it is being studied as a treatment
This RNA interference occurs naturally in plants, animals, and humans.
RNA interference is important for regulating the activity of genes (a
fundamental mechanism for controlling the flow of genetic
information). RNA interference (RNAi) interferes with mRNA, a natural
molecular switch, regulating gene expression in plants, animals and
humans, by "silencing" over-active or malfunctioning genes.
The ability to introduce foreign DNA into cultured cells with DNA gene
sequences has allowed us to assign functions to different genes and
understand the mechanisms that activate or redress their function. It
has made gene therapy research possible, like with the proteins Dicer
However, giving instructions on the genetic differences that determine
how a person responds to a drug will still have cancer medicine being
prescribed on a "trial-and-error" basis, with adverse drug reactions
remaining a major cause of injury and hospitalizations.
All the gene mutation or amplification studies can tell us is whether
or not the cells are potentially susceptible to this mechanism of
attack. The don't tell you if one drug is better or worse than some
other drug which may target this.
The cell is a system, an intergrated, interacting network of genes,
proteins and other cellular constituents that produce functions. You
need to analyze the systems' response to drug treatments, before you
find clinical responders.
Genetic profiles cannot discriminate differing levels of anti-tumor
activity occurring among different targeted therapy drugs. Nor can
they identify situations in which it advantageous to combine a
targeted drug with other types of conventional cancer drugs.
Two years ago, three federal agencies, NCI, FDA, and CMS, announced a
program to try to identify biological indicators, or biomarkers, which
may indicate whether a cancer patient is likely to benefit from a
given anti-cancer therapy, or even whether they will suffer from
certain side effects.
We have the biomarkers for who will respond so we don't give these
powerful and expensive medicines to those who won't. Technologies,
developed over the last twenty years by private researchers, hold the
key to solving some of the problems confronting a healthcare system
that is seeking ways to best allocate available resources while
accomplishing the critical task of matching individual patients with
the treatments most likely to benefit them.