Future Directions in Brain Tumor Research and Treatment - Dr Bopanna K M

Heterogeneity is probably the most defining factor in addressing the complex topic of brain tumours. Malignant brain tumours are diverse in their morphology and cellular pathways while being shielded by the blood-brain barrier, which renders effective systemic therapy a Herculean task with a grim prognosis.

At present, most patients receive a generalized protocol of resective surgery followed by chemotherapy and radiation. The role of a tailored approach using precision medicine to treat brain tumours is the need of the hour to improve the outcomes of this devastating disease.

It is estimated that approximately 65,000 non-malignant and 25,000 malignant brain tumours are diagnosed annually in the US, and this burden is likely increasing in keeping with the overall incidence of tumours worldwide.

Future Directions: Brain Tumour Diagnosis and Treatment

The Neurooncological approach to a brain tumour requires strategizing treatment into stages, acknowledging that each stage brings its own unique set of multidisciplinary challenges with the common goals of tumour control and neural preservation to optimize the patient’s functional outcome.

The following is a brief insight into the promising current research in treating brain tumours.

At the diagnosis stage, AI with deep learning techniques in the field of Radiomics is increasingly being adapted to elicit zones of tumour extension within the brain, which aids in surgical and radiation planning.

During the initial stage of treatment, attaining a maximal safe resection, dexterous microsurgical removal of tumour from within an intricate mesh of critical brain structures benefits from research in Radiomics.

Radiomic data on tumour distribution and eloquent neural networks in tandem with intraoperative electrophysiological monitoring during resection optimizes the extent of tumour resection.

Fluorescence-guided resections with Immunofluorescence imaging using targeted antibodies against glioma cell lines offer improved intraoperative visualization of tumour tissue, thus extending the margins of glioma resection.

These resections are further aided by the advances in Exoscopic and Endoscopic fluorescence imaging techniques. Intraoperative treatment of the post-resection cavity includes the use of Radioactive gamma-emitting tiles layered in the brain along the resection margins to further sanitize the peripheral region of infiltrating tumour cells.

At the tissue analytic stage, establishing a comprehensive gene-based diagnosis is a work in progress that will become the standard of care for precision medicine in the treatment of gliomas. There are several established and dynamic glioma genetic atlas compilations to aid in this endeavour.

Based upon genetic configuration targeted therapy using drugs such as the MEK1/2 inhibitor Selumetinib in BRAF duplicated low-grade gliomas and mTOR pathway inhibitor.

Evorolimus to treat Subependymal giant cell astrocytoma have proved to be game-changing in their efficacy and limiting neurotoxicity from traditional chemotherapy. A limitation of this modality at present is the need for prolonged administration of targeted therapy.

Mutant IDH enzyme inhibitor Vorasidenib has shown promise in successfully targeting the commonly referred to IDH pathway in gliomas, establishing tumour control in glioma clinical trials.

Chimeric Antigen Receptor T (CAR-T) cell therapy utilizes the patient's own genetically reprogrammed T cells to specifically inhibit tumour growth and has been found to improve progression-free survival when administered in clinical trials.