|Stem cell culture (iStockphoto)|
Ramping up the heat on tumour cells could potentially boost the effectiveness of cancer treatments, say Dutch researchers.
The study by researchers based in The Netherlands, suggests that heating cancer cells between 41°C and 42°C may block a key DNA pathway and allow radiation and chemotherapy to more effectively thwart tumour growth.
But critics debate whether this heat level will work in the clinical setting.
Heating tumours a few degrees above body temperature in the lab breaks down a protein called BRCA2, which is essential for repairing double strands of DNA by a process known as homologous recombination, the researchers report in this week's Proceedings of the National Academy of Science.
This means the cells are less efficient at repairing damage caused by radiotherapy, chemotherapy or a new type of trial drug known as a PARP-1. The latter is used to treat rare cancers caused by defective BRCA genes such as some types of breast and ovarian cancer.
The researchers say their results, based on a range of cell cultures and animal models, shows that heat knocks out this DNA repair pathway in cancers with normal BRCA genes.
"We found that hyperthermia inhibits homologous recombination irrespective of the rare genetic BRCA2 mutation," says study co-author Dr Roland Kanaar from the Erasmus Medical Centre in Rotterdam.
This finding could potentially pave the way for the use of PARP-1 inibitors in combination with radio- or chemotherapy for a wider group of people, Kanaar says.
"While PARP inhibitors are now used in clinical trials for relatively rare tumours [caused by defective BRCA genes], our results suggest that tumours that can be efficiently heated should respond well to PARP inhibitors.
"So a drug developed for a small group of tumours with a specific genetic mutation, might now be useful for a larger group of tumours," he says.
Dr Gillian Mitchell, a clinical oncologist and director of the Familial Cancer Centre at the Peter McCallum Cancer Centre in Melbourne is trialling PARP-1 drugs in patients with breast cancer caused by defective BRCA genes.
While the Dutch research is "very early days from the petri dish to the person", Mitchell says it offers a new way of thinking for researchers working in the field.
"The big question in clinical trials is whether you can expand PARP inhibitors out to people that don't have the [BRCA] gene mutation," says Mitchell.
"At the moment we've been struggling with just how to identify tumours with this pathway and bashing our heads trying to identify them, whereas this [research] is suggesting … that you don't need to try to find them, you can make them susceptible," says Mitchell.
She says the technique may be useful for the treatment of localised tumours, but a lot more research is needed to get the concept into the clinic.
"We need to understand a lot more about what heating the cells means and the potential ramifications of that."
She says there are a number of questions that need to be answered to ensure the treatment actually works and doesn't cause side-effects.
"There are a lot of technical problems between now and using it in the clinic if the specific areas you want have to be heated to a specific temperature."
Heating not easy in reality
Professor Kum Kum Khanna from the Queensland Institute of Medical Research , says the concept of using hyperthermia to sensitise cancer cells isn't new.
"[This study] has potential based on laboratory-based evidence, but I would await positive outcomes from clinical trials whether this would be accepted as a treatment," says Khanna, who studies DNA damage and repair pathways and their impact on cancer.
Khanna says heating tumour cells in the clinical setting is a major hurdle.
"Systemic tumours are very difficult because you can't reach 43°C without having an outside temperature of 54° or above, which would burn the patient," she says.
Tej Pandita, Professor of Radiation Oncology at South Western Medical Center in Dallas, also urges caution about the study results.
Pandita says the paper's finding that a temperature of 42°C sensitises cancer cells is "inconsistent with existing literature."
He says previous research on animal studies published by his team in 2005 showed that temperatures of 42°C did not degrade proteins.
All clinical trials to heat tumours using electrodes or other methods have failed, he adds.
One of the researchers in the Dutch study is an employee of AstraZenica, which contributed the drugs and analytic tools used in the research.