This is a sobering episode that traces the history of the treatment of brain cancer – principally malignant glioma, since it is the most common diagnosis in a thankfully rare oncology indication – and how, unlike many of the indications we have discussed, the treatment options have been limited. The diagnosis of brain cancer often takes too long, partly because headaches and behavioural changes divert patient referrals to other specialities before patients end up at the door of a neurosurgeon after a CT scan. Surgical removal of tumours, chemotherapy and radiation then remained the staple of care for decades. Even the Gliadel wafer was a combination of these older interventions.

And while surgical debulking, chemo- and radiotherapy will remain in the treatment armoury for brain cancers, more recently there have been developments from biotech and pharma companies that are changing the treatment landscape. The recent approval of the BRAF, MEK and RAF kinase inhibitors that combine specific tumour-associated metabolic inhibition and the molecular genetic profile of tumours have brought modern drug discovery and development to the treatment of brain cancer. But there remain significant challenges in the form of access of new agents to tumours in the brain because of the blood-brain barrier. Even here, medicinal chemists are turning their attention to optimizing the brain penetrant potential of new molecules.

To bring us up to date, and offering much future hope, there are the clinical trials of classes of agents that have proven their worth in other oncology indications like PARP inhibitors, the PD-1 inhibitors, immune-oncology in general, and even CAR-T cellular therapies, that will hopefully add to the diversity of therapeutic options to treat brain cancer. While individual case reports are interesting, we also discuss one remarkable recently publicized combination of many current and experimental therapies that has galvanized hope for these patients.

This episode is dedicated to the patients who have sadly succumbed to brain cancer, including Jacob Whitehead and Nick Bowen and their families. Our commiserations and hopes for the future.

Companies mentioned in this episode:
Eisai, Inc., Novartis, AG, Day One Biopharmaceuticals, Servier, Medicenna Therapeutics, AnHeart Therapeutics, NeoImmuneTech, Nerviano Medical Sciences, Merck KGaA, Aveta Biomics, Moderna, Inc. Merck & Co., Inc.

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