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Integrating Systemic Therapies into the Multimodality Therapy of Patients with Craniopharyngioma

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The integration of targeted therapy into the multimodal management of craniopharyngiomas represents a significant advancement in the field of neuro-oncology. Historically, the management of these tumors has been challenging due to their proximity to vital brain structures, necessitating a delicate balance between tumor control and the preservation of neurological function. Traditional treatment modalities, such as surgical resection and radiation, while effective, carry their own set of risks, including potential damage to surrounding healthy tissues and the potential for long-term side effects. Recent insights into the molecular biology of craniopharyngiomas, particularly the discovery of the BRAF V600E mutation in nearly all papillary craniopharyngiomas, have paved the way for a targeted systemic treatment approach. However, advances have been limited for adamantinomatous craniopharyngiomas. The success of BRAF/MEK inhibitors in clinical trials underscores the potential of these targeted therapies not only to control tumor growth but also to reduce the need for more invasive treatments, potentially minimizing treatment-related complications. However, the introduction of these novel therapies also brings forth new challenges, such as determining the optimal timing, sequencing, and duration of targeted treatments. Furthermore, there are open questions regarding which specific BRAF/MEK inhibitors to use, the potential need for combination therapy, and the strategies for managing intolerable adverse events. Finally, ensuring equitable access to these therapies, especially in healthcare systems with limited resources, is crucial to prevent widening healthcare disparities. In conclusion, targeted therapy with BRAF/MEK inhibitors holds great promise for improving outcomes and quality of life for patients with BRAF-mutated craniopharyngiomas. However, additional research is needed to address the questions that remain about its optimal use and integration into comprehensive treatment plans.

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Authors and Affiliations

  1. Massachusetts General Hospital Cancer Center, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA

    David Gritsch MD, PhD & Priscilla K. Brastianos MD

  2. Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    Sandro Santagata MD, PhD

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Each author has substantially contributed to conducting the underlying literature review and drafting this manuscript. DG performed the primary literature review and drafted the manuscript for intellectual content. PB and SS have each contributed to the literature review and revised the manuscript for intellectual content.

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Correspondence to Priscilla K. Brastianos MD.

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DG and SS have no conflicts of interest or disclosures to report. PKB has consulted for Angiochem, Merck, Genentech-Roche, Lilly, Tesaro, ElevateBio, Dantari, Voyager Therapeutics, SK Life Sciences, Pfizer, ACI, Sintetica, Kazia, MPM, CraniUS, Axiom and InCephalo, serves on the Scientific Advisory Board for Kazia, has received grant/research support (to MGH) from Merck, Lilly, Mirati, BMS and Kinnate, and speaker’s honoraria from Merck, Genentech-Roche, Lilly and Medscape.

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Gritsch, D., Santagata, S. & Brastianos, P.K. Integrating Systemic Therapies into the Multimodality Therapy of Patients with Craniopharyngioma. Curr. Treat. Options in Oncol. 25, 261–273 (2024). https://doi.org/10.1007/s11864-023-01156-2

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