Nicola Curtin, Professor of Experimental Therapeutics, explains: the potential of PARP inhibitors to treat cancer has long been championed by my team at Newcastle University but in the early days of our project not everyone agreed.
New era in cancer treatment
It wasn’t until they were found to target cancer-specific weaknesses, by selectively killing breast and ovarian cancers caused by mutations in a gene called BRCA, that the pharmaceutical industry became interested.
Fast forward to today and I’m pleased to report our continued research, initiated in the 1990s, has not only led to the first drug of its kind being developed and trialled in Newcastle but has also heralded a new era in cancer treatment.
PARP has now been adopted as a key cancer target by the global pharmaceutical industry, and has reached patients across:
- the Americas
- Australasia and Asia
As many as eight PARP inhibitors are currently being developed, and major companies have invested around $385m in clinical trials to date. Since 2008, more than 7,000 patients have been treated with the drugs as part of the trials.
The work has been published widely, in journals including:
- JNCI (the Journal of the National Cancer Institute)
- Clinical Cancer Research
- Molecular Cancer Therapeutics
In 2010, the research underpinning the discovery and development of PARP inhibitors was formally recognised by Cancer Research UK. CRUK awarded their inaugural Translational Cancer Research Prize to the Newcastle PARP team “in recognition of the discovery and development of novel PARP inhibitors, specifically the achievement of the team in driving an initial scientific concept through medicinal chemistry and preclinical work, to first-in-man clinical studies”.
Targeting cancer weaknesses
The drugs are designed to target the weakness in cancers and work by blocking the action of PARP – an enzyme involved in the repair of damaged DNA.
By themselves, PARP inhibitors are unable to kill cancer cells but when used to target cancer cells that lack a protein normally produced by BRCA genes, which is also involved in DNA repair, the two factors act together to attack the cancer cell.
The cancer cells are no longer able to repair DNA damage and ultimately die, while leaving healthy cells unscathed. The treatment also has fewer side effects than chemotherapy.
PARP inhibitors also work in concert with conventional chemotherapy to attack other cancers. Our trials have proven the potential of PARP inhibitors in combination with chemotherapy drug, temozolomide.
Two of the 33 patients treated for malignant melanoma in the Phase I trial in 2003 and five out of 40 patients treated in the Phase II trial in 2005 are alive today and in remission, despite being diagnosed with incurable melanoma and having a life expectancy of just a few months when they were recruited to take part in the study.
According to the National Cancer Institute, between one in 400 and one in 800 women have a BRCA mutation. Of these, 60% or more will develop breast cancer and 15-40% will develop ovarian cancer.
With the continued work and dedication of our team, we are bringing new hope and new treatments to those affected by this devastating disease.
Professor Nicola Curtin
Telephone: +44 (0) 191 208 4415