Rick and all, I hope the Rituxan researchers are correlating Rituxan responses with p53 mutations [refer Nov "Blood"] so that they find some way to discriminate between those who might benefit from Rituxan and those who won't.
Better to do that than think that Rituxan doesn't achieve much. Which poor overall results might lead them to think, even though within those results there might be particular people who get great results - if only they could be identified beforehand. Old descriptors such as "follicular", "low grade" etc are useless as correlations.
Meanwhile, excitement in the antiangiogenesis field, with IDEC competitor Techniclone market capitalisation jumping. Not such a bargain for IDEC to buy another NHL opportunity now. Maybe still very cheap though.
Maurice
From Affymetrix thread:
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To: jabbo (680 ) From: JF Quinnelly
Monday, May 4 1998 11:59PM ET
Reply # of 681
MITMay/June '98 Technology Review, Stephen Hall writes:
"SCIENCE WRITERS HAVE EXPENDED A GREAT MANY words on "gene
chips," which are being touted as biological crystal balls that will diagnose future genetic
susceptibility to disease. Having contributed my share of adjectives to this futuristic
vision, I know how tempting it is to describe.
But technologies often travel the low road to widespread use, and while prognostic gene
chips may well be a routine feature of annual physical checkups in the future, a related
chip application has already entered the clinic through the back door. "Molecular
profiling" is one name this technology goes by, and these highly precise genetic tests do
not exactly predict the future. Rather, these chips assess the molecular stage of a
patient's disease, and may ultimately suggest which drugs the patient might respond to...
...Given its importance, clinicians would like to know the p53 status of every tumor
they're trying to treat. About two years ago, biochip-maker Affymetrix joined forces
with Oncormed, a cancer diagnostics company based in Gaithersburg, Md., to make
p53 testing one of the prototypes of chip technology. Their target: the coding region of
the human p53 gene, which possesses 1,262 base pairs of DNA-the chemical subunits
of the double helix that tell a cell how to make the p53 protein.
Affymetrix, based in Santa Clara, Calif., has created a p53 chip that measures slightly
less than 13 millimeters square~bigger than a thumbtack, but smaller than the standard
issue 32-cent stamp. Engineers at Afymetrix have subdivided this real estate into a
checkerboard of 20,000 "probe cells;' each bristling with a uniform carpet of millions of
identical DNA probes measuring 18 base pairs long. Using fluorescently labeled
reagents, prepared DNA from a tumor can be washed over the chip, and extremely
sensitive scanners are programmed to detect minuscule variations in intensity in the
checkerboard pattern-which arise from slight genetic changes in p53. Once the DNA
has been prepared, the test can be done in four hours.
Although p53 is only one of numerous genes implicated in the evolution of a tumor, it
has already been thrust into a prominent role in experimental cancer treatments. In April
of 1996, for example, Oncormed began using the Affymetrix chip to perform "molecular
staging"-that is, assessing the status of a tumor-in patients with head and neck cancers
prior to clinical testing of an experimental form ofgene therapy developed by Onyx
Pharmaceuticals. The therapy is in Phase II testing, and some patients have responded
favorably in preliminary results.
The ability to do molecular profiling, according to Leslie Alexandre, a vice president at
Oncormed, allows oncologists to determine both the virulence of a tumor and the extent
of its metastatic spread. "If there is a p53 mutation in the tumor," she says, "then you
would look at the lymph nodes and look for the fingerprint to see how far the tumor has
spread." Oncormed has reached agreements with RhonePoulenc Rorer and
Schering-Plough to do p53 testing associated with gene therapy trials.
The potential significance of such testing goes well beyond staging individual tumors.
Drug companies are intensely interested in ways of predicting which patients are likely to
respond to chemotherapy, and there is some evidence that p53-and molecular profiling
like it-may help identify patients likelier to respond. Not only will this allow drug
companies to achieve higher response rates in drugs being tested, but it may, Alexandre
says, provide a way to "resurrect" drugs that fail in Phase III trials by identifying a small
group for whom the drug is very effective..." |
