The
title of the article is: "Sequential treatment of drug-resistant tumors
with targeted minicells containing siRNA or a cytotoxic drug,"
which will
not win any awards for literary felicity. But this was the article
passed to me last night by a technologist friend and appearing in the
June
issue of Nature Biotechnology. He'd gotten it from his father, also an
engineer. His mother has Stage 4 lung cancer. I'm told the article is
circulating—since its publication June 28—among the community of people
who are
hoping for a cure and watching the clock. It's also getting some
interesting
attention from people who know the business and the science: It's in
the No. 1
spot on HotCites—a social bookmarking site for biomedical types.
The
substance of the article is that a company called EnGeneIC, in New South Wales,
Australia, has announced an ameliorative therapy for a broad range of cancers
that shows 100 percent survival and zero toxicity of mouse subjects with
xenografted human cancers over two years.
It's
very hard to judge the truth value of this from superficials. The lead author, Jennifer
MacDiarmid, and several of her
collaborators are principals in EnGeneIC, a corporation formed in 2001. So this
could be the gene industry equivalent of a press release. And yet ... and yet
there's that 100 percent survival claim, which is a very, very hard claim for a
scientist to make (at least a scientist with concern for his or her reputation
in a profession and an industry with a long memory) unless it's true. Plenty of
drugs—stuff out there saving lives daily—were initially presented with far less
startling claims of efficacy. Or to put it another way, if you're testing
known-good antibiotics against known nonresistant strains of bacteria in vivo,
you might approach 100 percent survival for a short-term study, but you'd
typically lose subjects due to adverse reactions and other unknowns, so you
probably wouldn't claim it.
Indeed,
in many ways, it's more credible to claim less than perfect results, and the
temptation to hedge that way, knowing that you are being judged by clever,
competitive peers, must be very great, even when making claims on behalf of a
company in which you have a material interest.
Unless
all the mice actually did survive, in which case, I guess you shrug, report the
result, open a split of the good champagne and proceed to human trials, as
these folks are apparently doing.
Specifically,
what they're claiming to have invented and now tested is a method for inserting
siRNAs, or small, interfering RNA duplexes,
into so-called minicells, derived from bacteria and targeted to
tumor-cell-surface receptors. siRNAs have been getting a lot of research
attention over the past decade because they can be used to silence gene
expression, so they figure in a lot of research involving "turning genes
on and off," and have long been discussed as offering a potential means
for nanosurgically altering the function of tumor and other misbehaving cells.
In
the EnGeneIC therapy, these siRNA-bearing targeted minicells are administered
in a first wave, during which they migrate to the tumor surface, penetrate
tumor cell walls and release their siRNA payloads, which then go to work
knocking down the tumor cell's emission of a resistance protein that defends it
against chemotherapy. A second wave of minicells is then administered to
deliver a chemotherapeutic/cytotoxic payload, which the tumor cells are now
defenseless against. The result, EnGeneIC says, verges on perfect: The tumors
die back, and because the targeted delivery system applies the cytotoxin
precisely, and in minuscule quantity, the mice thrive.
Clearly,
this is not a universal cure. In fact, it's not any kind of cure. Applying this
strategy would seem to require a very close understanding of tumor resistance
(though this is increasingly well understood), and depends on the ability to
devise and produce gene-modulating siRNA formulations tuned to work against
each evolved resistance mode. And apparently all it does is shrink tumors—it
doesn't attack the underlying propensity of particular organisms, in particular
conditions, to pop tumor cells. But it harks forward to a time when cancer may
become, in some ways like AIDS in Western nations, a "manageable
condition," allowing for long-term survival and high quality of life.
