Targeting the DNA Damage Response Machinery for Lung Cancer Treatment

Venugopala, Katharigatta N.

doi:10.3390/ph15121475

Cited by 12 publications

(6 citation statements)

References 130 publications

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“…Nearly all cases of SCLC exhibit either homozygous loss or inactivation of RB1, a key regulator of the G1-S cell cycle checkpoint, and TP53, which is essential for multiple DNA Damage Response (DDR) pathways. As a result, SCLC cells exhibit high expression levels of DDR proteins [ 19 , 49 ]. On this basis, numerous inhibitors of DNA repair have recently been created and subjected to assessment in both preclinical models and clinical trials as potential candidates for treating SCLC.…”

Section: Targeted Therapies In P53 and Rb Deficient Sclc Cellsmentioning

confidence: 99%

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

Papavassiliou,

Sofianidi,

Gogou

et al. 2024

IJMS

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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 TP53 and RB1, 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.

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Section: Targeted Therapies In P53 and Rb Deficient Sclc Cellsmentioning

confidence: 99%

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

Papavassiliou,

Sofianidi,

Gogou

et al. 2024

IJMS

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“…Many other genes known as BRCA-related genes also participate directly or indirectly. Mutations in the BRCA1/2 genes were observed in 5-10% of NSCLC cases [19]. The BRCA1 and BRCA2 regulate HR repair through the assembly of the DNA recombinase-RAD51 onto broken DNA ends at the site of double strand breaks (DSBs) and held up replication forks [20].…”

Section: Signalling Pathways Involves In Lung Cancermentioning

confidence: 99%

Unravelling the Triad of Lung Cancer, Drug Resistance, and Metabolic Pathways

Mohanty,

Pande,

Acharya

et al. 2024

Preprint

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Lung cancer, characterized by its heterogeneity, presents a significant challenge in ther-apeutic management, primarily due to the development of resistance to conventional drugs. This resistance is often compounded by the tumour’s ability to reprogram its metabolic pathways, a survival strategy that enables cancer cells to thrive in adverse conditions. This review article ex-plores the complex link between drug resistance and metabolic reprogramming in lung cancer, offering a detailed analysis of the molecular mechanisms and treatment strategies. It emphasizes the interplay between drug resistance and changes in metabolic pathways, crucial for developing effective lung cancer therapies. The review examines the impact of current treatments on metabolic pathways and the significance of considering metabolic factors to combat drug resistance. It highlights the different challenges and metabolic alterations in non-small cell lung cancer and small cell lung cancer, underlining the need for subtype-specific treatments. Key signalling pathways, including PI3K/AKT/mTOR, MAPK, and AMPK, have been discussed for their roles in promoting drug resistance and metabolic changes, alongside the complex regulatory networks involved. The article evaluates emerging treatments targeting metabolism, such as metabolic inhibitors, dietary management, and combination therapies, assessing their potential and challenges. It concludes with insights into the role of precision medicine and metabolic biomarkers in crafting personalized lung cancer treatments, advocating for metabolic targeting as a promising approach to enhance treatment efficacy and overcome drug resistance. The review underscores ongoing advancements and hurdles in integrating metabolic considerations into lung cancer therapy strategies.

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“…Many other genes, known as BRCA-related genes, also participate directly or indirectly. Mutations in the BRCA1/2 genes have been observed in 5-10% of NSCLC cases [20]. BRCA1 and BRCA2 regulate HR repair by facilitating the assembly of the DNA recombinase-RAD51 onto broken DNA ends at the site of double strand breaks (DSBs) and holding up replication forks [21].…”

Section: Signaling Pathways Involved In Lung Cancermentioning

confidence: 99%

Unravelling the Triad of Lung Cancer, Drug Resistance, and Metabolic Pathways

Mohanty,

Pande,

Acharya

et al. 2024

Diseases

View full text Add to dashboard Cite

Lung cancer, characterized by its heterogeneity, presents a significant challenge in therapeutic management, primarily due to the development of resistance to conventional drugs. This resistance is often compounded by the tumor’s ability to reprogram its metabolic pathways, a survival strategy that enables cancer cells to thrive in adverse conditions. This review article explores the complex link between drug resistance and metabolic reprogramming in lung cancer, offering a detailed analysis of the molecular mechanisms and treatment strategies. It emphasizes the interplay between drug resistance and changes in metabolic pathways, crucial for developing effective lung cancer therapies. This review examines the impact of current treatments on metabolic pathways and the significance of considering metabolic factors to combat drug resistance. It highlights the different challenges and metabolic alterations in non-small-cell lung cancer and small-cell lung cancer, underlining the need for subtype-specific treatments. Key signaling pathways, including PI3K/AKT/mTOR, MAPK, and AMPK, have been discussed for their roles in promoting drug resistance and metabolic changes, alongside the complex regulatory networks involved. This review article evaluates emerging treatments targeting metabolism, such as metabolic inhibitors, dietary management, and combination therapies, assessing their potential and challenges. It concludes with insights into the role of precision medicine and metabolic biomarkers in crafting personalized lung cancer treatments, advocating for metabolic targeting as a promising approach to enhance treatment efficacy and overcome drug resistance. This review underscores ongoing advancements and hurdles in integrating metabolic considerations into lung cancer therapy strategies.

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Targeting the DNA Damage Response Machinery for Lung Cancer Treatment

Cited by 12 publications

References 130 publications

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

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

Unravelling the Triad of Lung Cancer, Drug Resistance, and Metabolic Pathways

Unravelling the Triad of Lung Cancer, Drug Resistance, and Metabolic Pathways

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