Radiotherapy and chemotherapy have long been reference treatments for cancer. These therapies act in part by damaging the DNA of cancerous cells stopping replication and inducing cell death. With time, it’s possible that the cancerous cells acquire the ability to repair lesions and become resistant to treatment. This deregulation is characteristic of metastatic tumours.
Blocking this DNA repair mechanism would make cancerous cells more likely to respond to treatment and avoid the resistance phenomenon.
The concept : bait molecules to block DNA repair
It has been shown that DNA repair in cells relies on multiple, complex and interconnected signalling pathways. Targeting just one pathway is not efficient as the cell tackles the problem by taking another pathway. The idea of the “Recombination, repair and cancer” team led by Dr Marie Dutreix (CNRS / IC) at Institut Curie was to block the system before the repairing step, during the identification of the defective DNA by the cell machinery.
The team has since shown that by introducing small fragments of DNA mimicking fragments of damaged DNA into the cells it is possible to “capture” the enzymes in charge of pointing out these defects. The cellular system is overrun with the identification of too many defective DNA fragments which induces cell death.
Transforming discovery into therapy
The different steps
The most promising molecule called DT01 is currently being tested alongside radiotherapy on patients with a radiotherapy-resistant metastatic melanoma. This phase I clinical study (DRIIM protocol) is being led by Dr Christophe Le Tourneau (IC).
The first results show that the DT01 molecule is very well tolerated and shows signs of an “anti-cancer” efficiency in association with radiotherapy
Dr Marie Dutreix
These encouraging observations indicate a strong development potential for these molecules.
Key success factors
- Close collaboration between clinicians – radiobiologists – chemists – physicists
- Visionary institutional support via the incentive and collaborative research program (PIC – “Genetic instability and tumour radio resistance)
- The support of Curie Cancer and the creation of the DNA Therapeutics start up