TWO chemists have devised a way to whip up a dose of poison inside a cancer
cell. By killing malignant cells while sparing normal ones, the new technique
could knock out tumours without the side effects of traditional
chemotherapy.
These serious side effects occur because chemotherapy drugs often kill
healthy cells along with cancerous ones. To get around this problem, some drugs
target receptor chemicals on the surfaces of tumour cells. But most receptors
appear on the surface of normal cells, too. So researchers have begun targeting
strands of genetic material that are found only inside cancer cells.
For example, a cell translates the genes in its DNA into messenger RNA
(mRNA), which it then uses to make proteins. In cancer cells, the mRNA will be
slightly abnormal. Researchers are designing drugs that target such mRNA to
prevent it forming defective proteins.
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But this approach, called antisense therapy, has a drawback: it leaves the
cancer cells alive, allowing the tumour to spread once drug therapy stops. So
chemists Zhaochun Ma and John-Stephen Taylor of Washington University in St
Louis, Missouri, decided to take the method a step further and use the mutated
mRNA as a trigger to kill the cell.
To do this, Ma and Taylor propose to use two compounds: a non-toxic precursor
and a catalyst. The pair combine to produce a cell-killing drug. The precursor
is linked to a short stretch of single-strand DNA tailored to match the sequence
of the abnormal mRNA. The catalyst is linked to a longer stretch of similarly
matched DNA. Once inside the tumour cell, the two compounds should zip onto the
abnormal mRNA, come into contact, and release the drug.
So far, the researchers have shown that they can catalyse the production of a
type of molecule found in two different cell-killing drugs. The next step, Ma
says, will be to try a complete drug, and not just a part of it. They must also
show that the process works not just in a chemical solution, but inside living
cells.
Already the chemists have shown that if the DNA and mRNA strands fail to
match by a single base鈥攁 genetic typo鈥攖he poison production stops,
so the method ought to target disease cells very precisely. 鈥淓ventually we can
target all sorts of diseases if they have specific mRNA mutations,鈥� Ma says. 鈥淪o
this method, I think, could be applied very broadly.鈥�