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Selasa, 10 Mei 2011

Heat up tumours to back up cancer therapy

  •                20:00 09 May 2011 by Ferris Jabr
  • For similar stories, visit the Cancer Topic Guide
It turns out some cancers can't stand the heat. Although studies have shown that heating tumours facilitates chemotherapy and radiation therapy, no one was sure why. Now, it appears that high temperatures dismantle enzymes that work against cancer drugs.
The discovery suggests that the right combination of drugs and heat will improve the effectiveness of chemotherapy.
Przemek Krawczyk at the University of Amsterdam, the Netherlands, and colleagues heated up tumour cells in Petri dishes. They also injected tumours into rats, and then heated the tumour-bearing hind limbs in a water bath set at 42 °C for 90 minutes.
The team discovered that high temperatures denature the BRCA2 protein, a DNA-repair enzyme. Ordinarily, BRCA2 fixes breaks in the DNA of cancer cells caused by cancer drugs, so dismantling BRCA2 leaves tumours more vulnerable to treatments.
"Cells have DNA repair pathways because they constantly accumulate DNA damage, so fixing it is good for normal cells, but DNA repair allows cancer cells to resist therapy that does DNA damage," explains co-author Roland Kanaar. "Now we know that hyperthermia [the elevation of body temperature] augments cancer treatments by inhibiting a specific DNA repair pathway."
"The logical next step is to think about drugs we could use in combination with hyperthermia, based on our findings," says Kanaar. The researchers suggest that hyperthermia would make an excellent ally for anti-cancer drugs that impair DNA-repair enzymes, such as PARP-1 inhibitors.
Journal reference: Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.1101053108

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