Growing tumour cells are always hungry. Researchers of
prof. Reuven Agami's group at the Netherlands Cancer Institute have
developed a method that uncovers for individual tumours which amino
acid is most limiting an thus most needed to keep the tumour
growing. Differential ribosome codon reading (diricore) makes it
possible to aim for tumour starvation by specific amino acid
deprivation. Agami's paper is published online in Nature on February
Human cancer cells use most of their energy and nutrients for
division and survival, and often exhaust one or few amino acids, to
a limiting level. Uncovering limiting amino acids in tumours can be
used for therapy, as further restriction will limit tumour growth.
However, it is extremely hard to find out which one is most
Reuven Agami: "Amino acid vulnerability is tumour-specific and
patient specific, but now we can measure restrictive amino acids in
almost every tumour!" Agami, together with his colleagues Dr.
Fabrizio Loayza-Puch and Dr. Koos Rooijers, makes two 'snapshots' -
one in the tumour tissue and one in the normal tissue - of
RNA-ribosome complexes, where proteins are produced. RNA is a
molecule that contains the instructions for the protein that is to
be built. A ribosome can read those instructions and carry them out
by linking the amino acids - of which the protein is composed - in
the right order. Agami: "The difference between the first and the
second snapshot shows the ribosomes that pile up at the RNA
instructions for the amino acid that is most restrictive. They are
waiting there longer for new supplies, until they can move on."
From theory to clinical practice
Once the restrictive amino acid in a tumour is known, further
restrain of supply of that amino acid will impact tumour
development in a specific manner. This can be done by adding
a substance that shuts off amino acid production, or by turning off
genes for the production of this particular amino acid. Keeping the
amino acid at low levels in the circulation by injecting an enzyme
that breaks down the amino acid, or even a special diet, is another
way. The group of Agami has demonstrated this principle for one
such restrictive amino acid in breast cancer cells using genetic
tools. Indeed, turning off the production of a restrictive
amino acid reduced tumour growth in animal models.
As of now there is no clinical treatment yet based on the diricore
technique, and this might take a couple of years. Agami: "There are
all kinds of inspiring possibilities, which we are going to
try hopefully with the help of Dutch funds for this research."