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Forecasting cancer recurrence, in a test tube... for now

A new discovery at the Faculty of Medicine could one day enable experts to provide guidance on how to prevent cancer recurrence.

Jan Balvan (on the right), the paper’s lead author, and Martina Raudenská work in a research team at the Faculty of Medicine.

Nobody wants to receive the news that a cancer that seemed to have been cured has now returned. Unfortunately, this does happen – but a discovery by experts from the Faculty of Medicine Masaryk University could change that. With the help of a new type of microscope, a team led by Michal Masařík can tell, at least in laboratory conditions, if prostate cancer treatment has been effective and the cancer cells have died, or if they are going to come back in a form even more insidious than before.

The treatment plan for successful chemotherapy is obvious: the patient is given drugs, the drugs kill the dangerous cells and the disease is gone. However, everyday experience shows it is not that simple. Not only are there more aggressive types of cancer that successfully resist treatment, but these most dangerous types of the disease also use different methods of resistance. This is the gist of a paper written by the Faculty of Medicine team and published several weeks ago by the journal Plos One.

Cannibal cells
It has been known for some time that stronger cancer cells sometimes consume weaker ones and use them as a source of energy to defend themselves against chemotherapy drugs. However, there previously was no way to observe this “cellular cannibalism”.

“After treatment, metabolic tests showed that the cancer cells were dead. However, we were not convinced: it looked rather as if they were hibernating. Unfortunately, there was no way to prove that,” says Jan Balvan, the lead author of the paper that describes this process as well as other mechanisms hitherto unknown.

A chance to try and prove the hibernation theory opened up when the laboratory received a new holographic microscope from the Tescan company for testing. Rather than just taking photographs, the device is able to monitor the samples over time for hours and make a video recording. This brought a dramatic change in how researchers viewed the problem.

The research proved that some cells protect themselves from drugs by engulfing other, weaker cells and using them as nutrients, but that was not all: the study also revealed other forms of interaction between cells that prevent a definitive cure of the disease they cause. “We also observed how two cells were able to join up to survive the unfavourable conditions, or how one cell used another as protection against the hostile environment,” describes Martina Raudenská, another of the paper’s authors.

A new and more dangerous form of cancer
Due to these processes, the disease can sometimes come back in an even more resistant form. In a bitter paradox, the treatment forces the cells to evolve more quickly and cooperate on finding advantageous mutations. It is unlikely that they would start cooperating were it not for the hostile environment.

All these new insights were gained by studying test-tube samples in prostate cancer research. The next step is for the physiologists to test their results on other types of the disease and on live models. If their findings are found to be valid outside a laboratory environment, it would mean that they could assess, at a relatively early stage of treatment (depending, of course, also on how early the treatment is started), whether cancer in a particular patient is likely to recur and recommend a plan that would decrease the likelihood of recurrence.

In this way, new information could help save patients’ energy, their time and their doctors’ time, and also money. “Again, we see that you cannot view tumours as a homogeneous issue. Every person is different and so is every tumour, and therefore treatment needs to be more targeted and personalised,” emphasizes Jaromír Gumulec, another research team member.

The team was able to make this progress in research thanks to a new holographic microscope that they received for testing from the Tescan company. It is a mutually beneficial partnership. The team can use technology that is currently in active use only at the Francis Crick Institute in London. The company, on the other hand, receives feedback as to what improvements and changes are needed before the microscope can be launched in serial production.