Researchers of the Netherlands Cancer Institute (NKI)
have developed a new combination therapy against lung- en colon
cancer. The details are published this week in the
journal Cell Reports.
The therapy is a another example of personalized medicine. In
personalized medicine, physicians and scientists no longer focus on
the location of a tumor, but on the specific genetic mutations that
caused cells to become cancerous. Around 20 percent of the patients
with lung cancer and 30 percent of the patients with colon cancer
have tumors with a mutation in the KRAS gene. This mutation affects
several protein pathways in the cell, causing rapid
KRAS mutations are hard to target with drugs. But there are drugs
available that affect the proteins which become deregulated due to
a KRAS mutation. Unfortunately, the individual effect of these
drugs is often weak. Molecular geneticist prof. dr. René Bernards
and his research group at the NKI started a search for a
combination therapy in which the drugs do have a strong effect when
given together. Bernards likes to explain this tactic by
using the analogy of a road map. On road maps, you can see that
there are often several ways by which you can get from one point to
another. Bernards: "Route A might be the easiest or fastest route.
But if route A is blocked, you will take route B. Tumors behave in
the same way: they prefer certain survival pathways. But if you
block this preferred pathway, using drugs, they will switch to a
different one. The trick is to not just block the preferred
pathway, but also alternative ones."
After thorough research the team discovered that both lung and
colon tumors with a KRAS mutation can effectively be treated with
the combination of a MEK inhibitor, like selumetinib, and a drug
that inhibits the proteins EGFR and ERBB2, like afatinib or
dacomitinib. This combination also proved to be effective in mouse
models. The discoveries of Bernards en his team are published today
in the journal Cell Reports.
The Netherlands Cancer Institute is both a research institution
and a specialized cancer hospital. This enables quick translation
of research outcomes to the clinic. Prof. dr. Bernards works in
close collaboration with medical oncologist prof. dr. Jan
Schellens. Schellens will start a clinical trial with the new
combination therapy this April. He has high expectations of it.
Schellens: "The individual drugs that make up this combination
therapy have already been thoroughly tested. We know about their
efficacy and their safety. The safety of the combination of these
drugs does still have to be determined. But we believe this new
therapy to be an even stronger concept than the successful
combination therapy for patients with colon cancer and a BRAF
mutation, which we recently developed. When I look at the strength
of the biological data professor Bernards gathered, I certainly
expect that this therapy will work in human patients."