p53의 구조와 기능, 변이 양상 및 소세포폐암에서의 치료 전략

초록

Tumor suppressor p73 is a key regulator of genomic stability and cellular stress response, including DNA damage and oncogenic signaling. Although originally considered an oncogene, p53 is now recognized for its critical tumor suppressive roles, such as inducing cell cycle arrest, apoptosis, and DNA repair. This review summarize the structure and function of p53, with a focus on the DNA binding domain, where most cancer associated mutations occur. These mutations often result in both loss of function and gain of function properties, which contribute to tumor progression and therapeutic resistance. Small cell luing cancer (SCLC) is one of the cancer types with the highest frequency of p53 alteration, with over 90% of tumors harboring mutations or deletions. The loss of wild type p53 function in SCLC leads to uncontrolled proliferation, genomic instability, and resistance to treatment. Also, its classical function, p53 also regulates metabolism, stemness, and immune responses. Mutant p53 promotes glycolysis and suppresses oxidative phosphorylation, thereby reinforcing the Warburg effect. Therapeutic strategies targeting p53 include reactivating mutant p53, destabilizing it via chaperone inhibition, and misuse synthetic lethality. Immunotherapeutic approaches, such as p53 based vaccines and immune checkpoint modulation, are also being investigated. However, it is important to note that mutant p53 can suppress antigen presentation and recruit immunosuppressive cells, contributing to immune evasion. This review highlight the multifaceted roles of p53 in SCLC and underscores its importance as a therapeutic target in cancer biology.

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