The Quest for Precision Medicine in Brain Tumours

Brain cancer has been a focal point of intensive research since the early 21st century. Primary brain and Central Nervous System (CNS) tumours — encompassing neoplasms within the brain and spinal cord — represent a diverse and intricate category of cancers. Brain and central nervous system cancer rank 19th?in the list of most frequent malignancies and 12th among the leading causes of cancer deaths as per the Global Cancer Observatory (GLOBOCAN) 2020 estimates.[1]. Brain tumours severely impact a patient's physical, cognitive, and psychological well-being. Brain tumours can originate in the brain (primary brain tumour) or elsewhere in the body and spread to the brain (secondary brain tumour). Grade I brain tumours are benign and slow growing while Grade IV are highly malignant and aggressive. A comprehensive understanding of both the type and grade of a brain tumour is crucial for designing optimal treatment strategies.

The prognosis for patients diagnosed with brain cancer remains grim and survival rates have shown little improvement over the years. While conventional treatment modalities (including surgery, chemotherapy, and various forms of radiation therapy) do exist, they often fall short in terms of efficacy. There remains a critical need for the development of targeted therapeutic approaches to improve patient outcomes. Precision medicine — referred to as individualized medicine, personalised medicine, or targeted therapy — fulfils the need for targeted therapy by delivering the right treatment to the right patient at the right time. Precision medicine facilitates the identification of specific biological, genetic, and molecular characteristics driving a patient’s tumour growth and?enabling the creation of targeted therapies that improve patient outcomes. These therapies target cancer-specific biomarkers, induce tumour regression and modulate the tumour microenvironment (TME). Precision medicine not only seeks to improve prognoses and survival rates but also to minimize collateral damage to healthy brain tissue, thereby preserving neurological function and quality of life. Precision medicine techniques are demonstrating significant potential in managing brain tumours that resist conventional therapies.

Despite advancements in brain cancer research, brain tumours pose substantial treatment challenges to the personalisation of clinical, diagnostic, and therapeutic strategies in neuro-oncology. These challenges arise from several factors, including the restrictive nature of the blood-brain barrier, the heterogeneous nature of brain tumours, and the inherently immunosuppressive environment of the brain. These obstacles necessitate innovative approaches to overcome and optimize the efficacy of personalized treatments for brain cancer.?Numerous targeted therapies for brain tumours are currently undergoing evaluation in phase I, phase II, and phase III clinical trials with major approaches being, inhibitors of programmed death-1 (PD-1), integrins, and angiogenesis via vascular endothelial growth factor (VEGF) or its receptors (VEGFR). Additionally, targeted treatments against the epidermal growth factor receptor (EGFR) and inhibitors of cyclin-dependent kinases (CDK) are being investigated. Modern trial designs in precision medicine, particularly 'basket' and 'platform' trials, are focused on advancing targeted treatments for patients with primary CNS tumours, paving the way for more effective and individualized therapeutic options.?CAR-T cell therapy — which leverages the body's innate immune system to precisely target and eradicate brain tumours — not only aims to eliminate existing tumours but also to prevent their recurrence by establishing long-term immune surveillance. Concurrently, dendritic cell vaccines have demonstrated significant potential in inducing robust and enduring immune responses, thereby providing sustained protection against tumour relapse.

All these innovations mark a significant leap forward in neuro-oncology, providing new hope for effective treatment outcomes. The cornerstone of these personalised therapies is the use of biological cells that are safe, effective, and manufactured to cGMP (current Good Manufacturing Practice) standards for human administration. On a therapeutic scale, the required number of cells is substantial, often ranging from 0.2 million to 5 million per kilogram of the patient's body weight for a single dose.[2] This necessitates rigorous, aseptic and scalable cell production processes to meet the demands of individualised treatment protocols.

For over 40 years, DDE has been a trusted partner for leading biopharmaceutical companies in their pursuit of developing novel therapies. Through advanced equipment, expert services, and technical guidance, we empower biopharmaceutical companies to develop products with superior yields at reduced costs. DDE's automated and customizable bioreactors deliver optimal solutions for efficient cell expansion within a constrained timeframe while ensuring rigorous control over the process. DDE’s QbD (Quality by Design) approach results in a non-variable and healthy cell population. DDE is profoundly committed to empowering biopharmaceutical manufacturers to deliver "tailored treatments".

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Source:

1. International patterns and trends in the brain cancer incidence and mortality: An observational study based on the global burden of disease - PMC (nih.gov)

2. Dose-response correlation for CAR-T cells: a systematic review of clinical studies - PMC (nih.gov)

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