Jiang Qian, Xiao Jingyi, Hsieh Yao-Ching, Kumar Neha Love, Han Lei, Zou Yuntao, Li Huang
Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing 210093, China.
International Dentist Pathway, University of California, San Francisco, CA 94158, USA.
Biomedicines. 2024 Jul 19;12(7):1610. doi: 10.3390/biomedicines12071610.
Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies globally, representing a significant public health problem with a poor prognosis. The development of efficient therapeutic strategies for HNSCC prevention and treatment is urgently needed. The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved transduction network in eukaryotic cells that promotes cell survival, growth, and cycle progression. Dysfunction in components of this pathway, such as hyperactivity of PI3K, loss of PTEN function, and gain-of-function mutations in , are well-known drivers of treatment resistance and disease progression in cancer. In this review, we discuss the major mutations and dysregulations in the PAM signaling pathway in HNSCC. We highlight the results of clinical trials involving inhibitors targeting the PAM signaling pathway as a strategy for treating HNSCC. Additionally, we examine the primary mechanisms of resistance to drugs targeting the PAM pathway and potential therapeutic strategies.
头颈部鳞状细胞癌(HNSCC)是全球最常见的恶性肿瘤之一,是一个预后不良的重大公共卫生问题。迫切需要开发有效的治疗策略来预防和治疗HNSCC。PI3K/AKT/mTOR(PAM)信号通路是真核细胞中高度保守的转导网络,可促进细胞存活、生长和周期进展。该通路成分的功能障碍,如PI3K的过度活跃、PTEN功能的丧失以及 中的功能获得性突变,是癌症治疗耐药和疾病进展的众所周知的驱动因素。在这篇综述中,我们讨论了HNSCC中PAM信号通路的主要突变和失调。我们强调了涉及靶向PAM信号通路抑制剂的临床试验结果,作为治疗HNSCC的一种策略。此外,我们研究了对靶向PAM通路药物耐药的主要机制和潜在的治疗策略。