In a major cancer breakthrough, scientists have discovered a molecular mechanism that allows tumours to develop resistance to chemotherapy.
This research has been reported in the journal Cancer Cell, with scientists from the Massachusetts Institute of Technology (MIT) in Cambridge having documented the process.
The new discovery will act as a backup when a specific gene called p53 is missing. This gene usually helps healthy cells prevent mutations.
Backing up the system usually is a pathway called MK2, which allows cells with damaged DNA to repair themselves.
The study ultimately found that a measure of the MK2 pathway performed excellently in terms of predicting which patients responded to chemotherapy.
In the absence of p53, cell division continues during chemotherapy, ensuring that cancer cells continue to proliferate after the process has be completed.
Michael Yaffe, a professor of biology and biological engineering, elaborated on the process:
“I would argue that this particular RNA-binding protein is really what makes tumor cells resistant to being killed by chemotherapy when p53 is not around.”
Prof. Yaffe and colleagues discovered that when p53 is missing – as it is in about half of all tumours – the MK2 pathway takes over.
They thus suggest that targeting the backup system could make p53-deficient tumour considerably more susceptible to chemotherapy.
Yaffe states that researchers discovered that the MK2 pathway does not take over all of p53’s function, only part of it:
“It only rescues the bad parts of p53’s function, but it doesn’t rescue the part of p53’s function that you would want, which is killing the tumour cells.”
The researchers found that measuring levels of the mRNA for Gadd45 and p27 could also help predict which patients are likely to respond to chemotherapy.
In a trial of patients with stage 2 lung cancers, it was demonstrated that those with high levels of mRNA for Gadd45 and p27 did not respond as well to chemotherapy as patients who had low levels of both.
Prof. Yaffee indicates that this measure could be utilised as a surrogate for the presence or absence of the pathway and concludes:
“In this trial, it was very good at predicting which patients responded to chemotherapy and which patients didn’t.”
The study shows that cancer cells have molecular mechanisms that help them maintain their integrity and survive.
It is hoped that this research will lead to a greater understanding of cancer in the continuing battle against the debilitating condition.
There are over 160,000 deaths from cancer every year in the UK alone.