Western research has revealed how a simple test may now predict who will respond better to chemotherapy when dealing with lung cancer, thanks to a link between the absence of a specific protein and improved patient outcomes.
Dr. Matthew Cecchini, a pathology resident at London Health Sciences Centre, discovered patients who undergo chemotherapy and surgery for lung cancer experience significantly improved survival rates when their tumour lacks the retinoblastoma (RB) tumour suppressor protein. Survival rates for those patients stand at 92 per cent at five years, compared to average survival rates of 49 per cent for those patients who had the protein.
What is odd to Cecchini, however, is the fact the RB protein is traditionally understood to help regulate cell division, preventing the growth of abnormal cells.
“Its normal function is suppressing tumours, which is what it does normally in your body – it’s preventing cancer from happening,” said Cecchini, whose study recently appeared in Human Pathology. “Conventional wisdom is you want to keep it. But we found patients who lose it do better.”
Under the leadership of Lawson Health Research Institute’s Dr. Fred Dick, Cecchini and a collaborative team of researchers performed a study on 91 lung cancer patients who underwent chemotherapy and surgery. Admittedly, Dick was also surprised with the results.
“RB protein is a very important growth regulator. The assumption is that if you lose it, it must always be a bad thing,” said Dick, a Western Biochemistry professor. “The surprise is, if you have a cancer that is physically missing the protein, you actually do better in your treatment. Most of the time cancers do not mutate the gene for RB. They usually find other ways of ‘turning off’ the function of the protein, and that’s sort of their way of growing.
“One way or another, you have to overcome growth suppression by the RB protein in order for a cell to become a cancer cell. What’s surprising is, if you lose it, it has this phenomenal effect in your response to chemotherapy.”
This new information may help predict which patients will respond best to chemotherapy. Testing the tumour can determine the best treatment plan for individual patients. In addition, the research may provide rationale for developing agents that target the RB protein in order to make all lung cancer cases more sensitive to chemotherapy.
“Cancer is like evolution. It’s evolved to proliferate; it finds the best way to do that,” Cecchini said. “The prognosis of lung cancer is poor and the therapies have lots of side effects. Chemo is never good. In some people, you’d want to know whether this treatment is going to be useful or not. It may not work as well, so is there something that would work better?”
For patients who do have the protein, yet do worse, is there something that can be done to target that protein – in essence, a drug treatment to shut it down? This creates an interesting dilemma.
“It gets back to the idea this is a tumour suppressor. Do you really want to make a drug against a tumour suppressor?” Cecchini asked. “It needs to be done in a selective way. It does a lot of things that are good. We’re looking whether we can target one part of that.”
Dick said a test would be like “a looking glass” for patients and doctors alike.
“You could say you should do chemo because your chances of a cure are very high, and for people who still have the RB protein they are in the general population, but there are others options as well,” he said. “Chemo is pretty harsh and, for some people, the decisions they make are more palliative – ‘I will live out the days the best I can, I don’t want them being in the hospital getting chemo,’ or they decide to go for chemo.”
The next phase in the study is to test the findings in a larger patient cohort, looking at the underlying mechanisms of RB protein to understand what makes certain patients more responsive to chemotherapy.