Glioblastoma Standard of Care: Effects on Tumor Evolution and Reverse Translation in Preclinical Models
Louis T Rodgers1, John L Villano2,3,4,5, Anika M S Hartz6,7
1Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
Abstract:
Glioblastoma (GBM) presents a significant public health challenge as the deadliest and most common malignant brain tumor in adults. Despite standard-of-care treatment, which includes surgery, radiation, and chemotherapy, mortality rates are high, underscoring the critical need for advancing GBM therapy. Over the past two decades, numerous clinical trials have been performed, yet only a small fraction demonstrated a benefit, raising concerns about the predictability of current preclinical models. Traditionally, preclinical studies utilize treatment-naïve tumors, failing to model the clinical scenario where patients undergo standard-of-care treatment prior to recurrence. Recurrent GBM generally exhibits distinct molecular alterations influenced by treatment selection pressures. In this review, we discuss the impact of treatment-surgery, radiation, and chemotherapy-on GBM. We also provide a summary of treatments used in preclinical models, advocating for their integration to enhance the translation of novel strategies to improve therapeutic outcomes in GBM.
Insights
Glioblastoma treatment needs improvement. Preclinical models should include therapies used in patients to better predict new glioblastoma (GBM) treatments.
Area of Science:
- Neuro-oncology
- Cancer Research
- Translational Medicine
Background:
- Glioblastoma (GBM) is the most common and deadliest adult malignant brain tumor.
- Standard treatments (surgery, radiation, chemotherapy) have limited efficacy, leading to high mortality.
- Current preclinical models often fail to predict clinical success due to lack of treatment exposure.
Purpose of the Study:
- To review the impact of standard treatments on glioblastoma.
- To highlight the limitations of current preclinical models in reflecting clinical recurrence.
- To advocate for incorporating treatment-induced changes in preclinical GBM research.
Main Methods:
- Literature review of glioblastoma treatment modalities.
- Analysis of standard-of-care impact on tumor biology.
- Summary of preclinical treatment strategies.
Main Results:
- Standard treatments significantly alter GBM molecular profiles.
- Recurrent GBM differs substantially from treatment-naïve tumors.
- Existing preclinical models do not adequately represent treatment-induced GBM evolution.
Conclusions:
- There is a critical need for advanced glioblastoma therapies.
- Preclinical models must incorporate the effects of prior treatments.
- Integrating treatment-experienced models will improve the translation of novel GBM strategies.
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