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Heat to augment cancer therapy

Heat to augment cancer therapy

We discovered that local mild hyperthermia attenuates the DNA damage response by inhibiting homologous recombination through degradation of the BRCA2 protein. Our discovery explains the clinical observation that hyperthermia sensitizes tumors to DNA damage-inducing therapies. We showed that mild hyperthermia sensitizes innately homologous-proficient tumors to PARP-1 inhibitors, thus irrespective of genetic BRCA deficiency. These finding are very promising as they suggest that use of PARP-1 inhibitor precision medicines can be extended beyond the limited group of patient who are BRCA mutation carriers. Here we want to find define the molecular mechanism through which the BRCA2 is degraded and make use of that knowledge to guide the design of optimize hyperthermia protocols. We will employ molecular biology, quantitative cell biology and proteomics techniques.

Hyperthermia system

Relevant publications

Krawczyk et al., Mild hyperthermia inhibits homologous recombination, induces BRCA2 degradation, and sensitizes cancer cells to poly (ADP-ribose) polymerase-1 inhibition. Proc. Natl. Acad. Sci. USA 108, 9851-9856.

van den Tempel et al.,  Improving efficacy of hyperthermia in oncology by exploiting biological mechanisms.  Int. J. Hyperthermia, in press.