Academic Journal

Metabolic barriers in non-small cell lung cancer with LKB1 and/or KEAP1 mutations for immunotherapeutic strategies

التفاصيل البيبلوغرافية
العنوان: Metabolic barriers in non-small cell lung cancer with LKB1 and/or KEAP1 mutations for immunotherapeutic strategies
المؤلفون: Ichidai Tanaka, Junji Koyama, Hideyuki Itoigawa, Shunsaku Hayai, Masahiro Morise
المصدر: Frontiers in Oncology, Vol 13 (2023)
بيانات النشر: Frontiers Media S.A., 2023.
سنة النشر: 2023
المجموعة: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
مصطلحات موضوعية: immune checkpoint blockade, NSCLC, LKB1, KEAP1, metabolic barriers, glycolysis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: Currently, immune checkpoint inhibitors (ICIs) are widely considered the standard initial treatment for advanced non-small cell lung cancer (NSCLC) when there are no targetable driver oncogenic alternations. NSCLC tumors that have two alterations in tumor suppressor genes, such as liver kinase B1 (LKB1) and/or Kelch-like ECH-associated protein 1 (KEAP1), have been found to exhibit reduced responsiveness to these therapeutic strategies, as revealed by multiomics analyses identifying immunosuppressed phenotypes. Recent advancements in various biological approaches have gradually unveiled the molecular mechanisms underlying intrinsic reprogrammed metabolism in tumor cells, which contribute to the evasion of immune responses by the tumor. Notably, metabolic alterations in glycolysis and glutaminolysis have a significant impact on tumor aggressiveness and the remodeling of the tumor microenvironment. Since glucose and glutamine are essential for the proliferation and activation of effector T cells, heightened consumption of these nutrients by tumor cells results in immunosuppression and resistance to ICI therapies. This review provides a comprehensive summary of the clinical efficacies of current therapeutic strategies against NSCLC harboring LKB1 and/or KEAP1 mutations, along with the metabolic alterations in glycolysis and glutaminolysis observed in these cancer cells. Furthermore, ongoing trials targeting these metabolic alterations are discussed as potential approaches to overcome the extremely poor prognosis associated with this type of cancer.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2234-943X
Relation: https://www.frontiersin.org/articles/10.3389/fonc.2023.1249237/full; https://doaj.org/toc/2234-943X
DOI: 10.3389/fonc.2023.1249237
URL الوصول: https://doaj.org/article/8a6f383838d34ee8a6af0909a119949d
رقم الانضمام: edsdoj.8a6f383838d34ee8a6af0909a119949d
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2234943X
DOI:10.3389/fonc.2023.1249237