P53 and Rb Aberrations in Small Cell Lung Cancer (SCLC): From Molecular Mechanisms to Therapeutic Modulation

The genes coding for the tumor suppressors p53 and retinoblastoma (Rb) are inactivated in the vast majority of small cell lung cancer (SCLC) tumors. Data support the notion that these two deleterious genetic events represent the initial steps in the development of SCLC, making them essential for a l...

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Bibliographic Details
Published in:International journal of molecular sciences 2024-02, Vol.25 (5), p.2479
Main Authors: Papavassiliou, Kostas A, Sofianidi, Amalia A, Gogou, Vassiliki A, Anagnostopoulos, Nektarios, Papavassiliou, Athanasios G
Format: Article
Language:English
Subjects:
Apoptosis
Biology
Cell cycle
Cyclin-dependent kinases
Development and progression
DNA damage
Enzymes
Genes
genetic alterations and aberrations
Health aspects
Humans
Kinases
Lung cancer
Lung cancer, Small cell
Lung Neoplasms - genetics
Mutation
mutations
p53
Pemetrexed
Phosphatase
Protein expression
Proteins
Retinal Neoplasms
Retinoblastoma
Review
RNA polymerase
Senescence
small cell lung cancer
Small Cell Lung Carcinoma - drug therapy
Transcription factors
Tumor proteins
Tumor Suppressor Protein p53 - genetics
Tumors
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Summary:The genes coding for the tumor suppressors p53 and retinoblastoma (Rb) are inactivated in the vast majority of small cell lung cancer (SCLC) tumors. Data support the notion that these two deleterious genetic events represent the initial steps in the development of SCLC, making them essential for a lung epithelial cell to progress toward the acquisition of a malignant phenotype. With the loss of and , their broad tumor suppressive functions are eliminated and a normal cell is able to proliferate indefinitely, escape entering into cellular senescence, and evade death, no matter the damage it has experienced. Within this setting, lung epithelial cells accumulate further oncogenic mutations and are well on their way to becoming SCLC cells. Understanding the molecular mechanisms of these genetic lesions and their effects within lung epithelial cells is of paramount importance, in order to tackle this aggressive and deadly lung cancer. The present review summarizes the current knowledge on p53 and Rb aberrations, their biological significance, and their prospective therapeutic potential, highlighting completed and ongoing clinical trials with agents that target downstream pathways.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms25052479