Aging and senescence: Key players in brain tumor progression and drug resistance.

in Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy by Chao Zhang, Neha, Jiaqi Zhang, Prashant, Xiaodie Li, Sarad Kumar Mishra, Joshua Fleishman, Suhel Parvez, Saurabh Kumar Jha, Min Huang

TLDR

  • The study explores the relationship between aging and brain tumor progression, highlighting the critical role of age-related genetic mutations, cellular pathways, and tumor microenvironment in tumorigenesis and treatment resistance.
  • The review emphasizes the need for personalized treatment strategies and further research to address age-related molecular changes and improve treatment outcomes for elderly patients.

Abstract

Aging plays a critical role in the development, progression, and therapeutic challenges associated with brain tumors, particularly glioblastomas (GBM). As the population ages, the incidence of brain tumors, including GBM, increases, with aging emerging as a significant prognostic factor influencing survival outcomes. This review examines the molecular mechanisms linking aging and brain tumor progression, with a specific focus on glioblastomas. We explore how age-related genetic mutations, alterations in cellular pathways, and changes in the tumor microenvironment (TME) contribute to tumorigenesis and treatment resistance. Furthermore, we highlight the impact of key signaling pathways, such as the PI3K/AKT/mTOR, p53, and EGFR/PTEN, which are frequently dysregulated in both aging and brain tumors. Despite the growing recognition of aging as a critical factor in brain tumor biology, therapeutic strategies for elderly patients remain poorly defined, often due to underrepresentation in clinical trials and the complex interplay of comorbidities and treatment side effects. The review also discusses emerging therapeutic approaches, including targeted therapies and immunotherapies, which offer promise for improving treatment outcomes by addressing age-related molecular changes. Finally, we emphasize the importance of personalized treatment strategies and the need for further research to better understand the biological mechanisms underlying the aging-brain tumor relationship, ultimately aiming to enhance clinical management and patient quality of life.

Overview

  • The study explores the molecular mechanisms linking aging and brain tumor progression, specifically glioblastomas, and examines the role of age-related genetic mutations, cellular pathways, and tumor microenvironment in tumorigenesis and treatment resistance.
  • The review highlights the impact of key signaling pathways, such as PI3K/AKT/mTOR, p53, and EGFR/PTEN, which are frequently dysregulated in both aging and brain tumors.
  • The study emphasizes the importance of personalized treatment strategies and the need for further research to understand the biological mechanisms underlying the aging-brain tumor relationship, ultimately aiming to enhance clinical management and patient quality of life.

Comparative Analysis & Findings

  • The study reveals that aging plays a critical role in the development, progression, and therapeutic challenges of brain tumors, including glioblastomas.
  • The results show that age-related genetic mutations, alterations in cellular pathways, and changes in the tumor microenvironment contribute to tumorigenesis and treatment resistance.
  • The review highlights the impact of key signaling pathways, such as PI3K/AKT/mTOR, p53, and EGFR/PTEN, which are frequently dysregulated in both aging and brain tumors.

Implications and Future Directions

  • The study emphasizes the need for therapeutic strategies that address age-related molecular changes, such as targeted therapies and immunotherapies, to improve treatment outcomes.
  • The review highlights the importance of personalized treatment strategies and the need for further research to better understand the biological mechanisms underlying the aging-brain tumor relationship.
  • The study underscores the need for further research to address the underrepresentation of elderly patients in clinical trials and the complex interplay of comorbidities and treatment side effects.
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