Immunotherapy-based therapy as a promising treatment for EGFR-mutant advanced non-small cell lung cancer patients after EGFR-TKI resistance

Ding, Jianghua; Ding, Xinjing; Leng, Zhaohui

doi:10.1080/14737140.2023.2170879

Cited by 6 publications

(3 citation statements)

References 69 publications

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“…Therefore, combining EGFR or c-Met TKIs with anti-PD1/PD-L1 immunotherapy for DUSP22-depleted EGFRdel-driven mouse lung tumors appears promising. However, several clinical trials have not shown significant benefits from PD-1/PD-L1 blockade alone or with an EGFR TKI in EGFR mutant lung cancer patients [ 48 ]. Further study is necessary to discover improved treatment strategies for EGFR mutant lung cancer patients with DUSP22 loss or downregulation.…”

Section: Discussionmentioning

confidence: 99%

DUSP22 inhibits lung tumorigenesis by suppression of EGFR/c-Met signaling

Lin,

Chang,

Liao

et al. 2024

Cell Death Discov.

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DUSP22, an atypical dual-specificity phosphatase enzyme, plays a significant role in regulating multiple kinase signaling pathways by dephosphorylation. Our study demonstrated that decreased DUSP22 expression is associated with shorter disease-free survival, advanced TNM (tumor, lymph nodes, and metastasis), cancer stage, and higher tumor grade in lung adenocarcinoma (LUAD) patients. Exogenous DUSP22 expression reduces the colony-forming capacity of lung cancer cells and inhibits xenograft tumor growth primarily by targeting EGFR and suppressing its activity through dephosphorylation. Knockdown of DUSP22 using shRNA enhances EGFR dependency in HCC827 lung cancer cells and increases sensitivity to gefitinib, an EGFR inhibitor. Consistently, genetic deletion of DUSP22 enhances EGFRdel (exon 19 deletion)-driven lung tumorigenesis and elevates EGFR activity. Pharmacological inhibition of DUSP22 activates EGFR, ERK1/2, and upregulates downstream PD-L1 expression. Additionally, lentiviral deletion of DUSP22 by shRNA enhances lung cancer cell migration through EGFR/c-Met and PD-L1-dependent pathways. Gefitinib, an EGFR inhibitor, mechanistically suppresses migration induced by DUSP22 deletion and inhibits c-Met activity. Furthermore, cabozantinib, a c-Met inhibitor, reduces migration and attenuates EGFR activation caused by DUSP22 deletion. Collectively, our findings support the hypothesis that loss of DUSP22 function in lung cancer cells confers a survival advantage by augmenting EGFR signaling, leading to increased activation of downstream c-Met, ERK1/2, and PD-L1 axis, ultimately contributing to the progression of advanced lung cancer.

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Section: Discussionmentioning

confidence: 99%

DUSP22 inhibits lung tumorigenesis by suppression of EGFR/c-Met signaling

Lin,

Chang,

Liao

et al. 2024

Cell Death Discov.

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“…These drugs block the interaction between PD-L1 on cancer cells and programmed cell death-1(PD-1) on T cells, thus restoring the ability of the immune system to recognize and attack cancer cells [6]. Immunotherapy is quite promising but is not completely effective as it could cause immune-related adverse events (irAEs), including endocrine adverse events (eAEs), especially when administered for long [7,8]. Surgery, on the other hand, is a common treatment for lung cancer that involves the removal of the tumor and surrounding tissue.…”

Section: Introductionmentioning

confidence: 99%

A study on lung cancer using nabla discrete fractional-order model

Amilo,

Kaymakamzade,

Hınçal

2023

Mathematica Moravica

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This study proposes a nabla discrete fractional-order system of differential equations to model lung cancer and its interactions with lung epithelial cells, mutated cells, oncogenes, tumor suppressor genes, immune cells, cytokines, growth factors, angiogenic factors, and extracellular matrix. The proposed model can help predict cancer growth, metastasis, and response to treatment. Analytical results show the system is stable with a unique solution, and the model predicts that the immune system responds to cancer cells but eventually becomes overpowered. The numerical analysis employed the forward and backward Euler method and demonstrated that changes in parameter values have significant effects on the steady-state solution. The findings show that the growth of lung epithelial cells or their interaction with immune cells can cause an increase in the number of lung cancer cells. Conversely, an increase in cell death or a reduction in the interaction between lung epithelial cells and immune cells can decrease the number of lung cancer cells. The study highlights the usefulness of the nabla discrete fractional model in studying lung cancer dynamics.

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“…These drugs block the interaction between PD-L1 on cancer cells and PD-1 on T cells, enabling the immune system to recognize and attack cancer cells 6 . Although immunotherapy is a promising treatment, prolonged administration could lead to immune-related adverse events (irAEs), including endocrine adverse events (eAEs) 7,8 . On the other hand, surgery involves the removal of the tumor and surrounding tissue and is often curative for early-stage lung cancer, but may not be effective for advanced cases 9 .…”

mentioning

confidence: 99%

A fractional-order mathematical model for lung cancer incorporating integrated therapeutic approaches

Amilo,

Kaymakamzade,

Hincal

2023

Sci Rep

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This paper addresses the dynamics of lung cancer by employing a fractional-order mathematical model that investigates the combined therapy of surgery and immunotherapy. The significance of this study lies in its exploration of the effects of surgery and immunotherapy on tumor growth rate and the immune response to cancer cells. To optimize the treatment dosage based on tumor response, a feedback control system is designed using control theory, and Pontryagin’s Maximum Principle is utilized to derive the necessary conditions for optimality. The results reveal that the reproduction number $$(R_0)$$ ( R 0 ) is 2.6, indicating that a lung cancer cell would generate 2.6 new cancer cells during its lifetime. The reproduction coefficient $$(R_c)$$ ( R c ) is 0.22, signifying that cancer cells divide at a rate that is 0.22 times that of normal cells. The simulations demonstrate that the combined therapy approach yields significantly improved patient outcomes compared to either treatment alone. Furthermore, the analysis highlights the sensitivity of the steady-state solution to variations in $$k_5$$ k 5 (the rate of division of cancer stem cells) and $$k_{13}$$ k 13 (the rate of differentiation of cancer stem cells into progenitor cells). This research offers clinicians a valuable tool for developing personalized treatment plans for lung cancer patients, incorporating individual patient factors and tumor characteristics. The novelty of this work lies in its integration of surgery, immunotherapy, and control theory, extending beyond previous efforts in the literature.

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Immunotherapy-based therapy as a promising treatment for EGFR-mutant advanced non-small cell lung cancer patients after EGFR-TKI resistance

Cited by 6 publications

References 69 publications

DUSP22 inhibits lung tumorigenesis by suppression of EGFR/c-Met signaling

DUSP22 inhibits lung tumorigenesis by suppression of EGFR/c-Met signaling

A study on lung cancer using nabla discrete fractional-order model

A fractional-order mathematical model for lung cancer incorporating integrated therapeutic approaches

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