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PARP-inhibitor olaparib shows promise for glioblastoma

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Recently presented at the National Cancer Research Institute’s Cancer Conference (Liverpool, UK, 5–8 November 2017), a study led by Anthony Chalmers (University of Glasgow, UK) has successfully delivered olaparib to glioblastoma tumors, bringing research closer to finding a treatment.

The study investigated 48 patients with glioblastoma that had returned after initial treatment. Olaparib, a PARP-inhibitor that has been used to treat certain types of ovarian cancer was then given in combination with temozolomide, a chemotherapy drug.

The researchers observed that olaparib was able to penetrate both core and margins of recurrent glioblastoma despite failing to penetrate the intact blood brain barrier. They also discovered that the combination with low dose temozolomide was safe and tolerated, yielding encouraging 6 month progression-free survival rates. These results suggest a potential treatment strategy for glioblastoma tumors.

“Brain tumors are stubbornly difficult to treat and one of the main reasons for this is the blood-brain barrier, a natural filter that blocks the passage of drugs. But these results suggest that olaparib is able to leak through because this barrier is disrupted in glioblastoma. By showing that this drug reaches brain tumors, we are in a much stronger position to use it to make current treatments more effective,” explained Chalmers.
“While overall survival for cancer is improving, survival for brain tumors is still very low and the blood-brain barrier is a significant pharmacological obstacle. Experimental trials like this, which test new ways to reach these hard to treat tumors, are crucially important if we are to see more patients survive their cancer,” commented Nigel Blackburn (Cancer Research UK).

This study has already led onto two further clinical trials, PARADIGM and PARADIGM-2, which test olaparib in combination with radiotherapy and temozolomide in patients with newly diagnosed glioblastoma.

“We’re just beginning to realize the full potential of PARP inhibitors to tackle many different types of cancer, so it’s exciting to see that olaparib could potentially be used to treat glioblastoma in combination with chemotherapy and radiotherapy. These results are a huge step forwards in developing better treatments for patients with brain tumors, which claim too many lives every year,” concluded Susan Short (National Cancer Research Institute, UK).

Source:
NCRI press release

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