PD0325901, an ERK inhibitor, enhances the efficacy of PD-1 inhibitor in non-small cell lung carcinoma

Luo, Min; Xia, Yuhui; Wang, Fang; Zhang, Hong; Su, Danting; Su, Chaoyue; Yang, Chonglin; Wu, Shengxi; An, Sainan; Lin, Suxia; Fu, Liwu

doi:10.1016/j.apsb.2021.03.010

Cited by 22 publications

(13 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The PI3K/AKT/mTOR pathway can control PD-L1 expression. In lung squamous carcinoma or lung adenocarcinoma tissues with mutations in NRAS, KRAS, EGFR, BARF, PIK3CA, EML4-ALK, activation of PI3K/AKT/mTOR pathway and PD-L1 expression can be detected simultaneously [46]. PI3K/ AKT/mTOR-related inhibitors (e.g.…”

Section: Interaction Between Pi3k/akt/mtor Pathway and Pd-1/pd-l1mentioning

confidence: 99%

Clinical implications of the interaction between PD-1/PD-L1 and PI3K/AKT/mTOR pathway in progression and treatment of non-small cell lung cancer

Quan¹,

Yang²,

Zheng³

et al. 2022

J. Cancer

View full text Add to dashboard Cite

The discovery of immune checkpoints has been well known to provide novel clues for cancer treatments. Immunotherapy against the programmed cell death protein-1 (PD-1) /programmed death-ligand-1 (PD-L1), one of the most popular auxiliary treatments in recent years, has been applied in various tumor treatments, including non-small cell lung cancer (NSCLC). However, inevitable issues such as side effects and drug resistance emerge following the use of immune checkpoint inhibitors. The PI3K/AKT/mTOR pathway may participate in the regulation of PD-L1 expression. Abnormal PI3K/AKT/mTOR pathway activation results in increased PD-L1 protein translation, whereas PD-L1 overexpression can activate the PI3K/AKT/mTOR pathway inversely. Via downstream proteins, including 4E-BP1, STAT3, NF-κB, c-MYC, and AMPK in aberrant energy status, the PI3K/AKT/mTOR pathway can regulate PD-L1 post-transcription and translation. Besides, the regulation of the PI3K pathway by the PD-1/PD-L1 axis involves both tumor cells and the tumor immune microenvironment. Inhibitors targeting the PD-1/PD-L1 have been successfully applied in the treatment of gastrointestinal cancer and breast cancer. Meanwhile, drug resistance from alternative pathway activation also evidently affects clinical progress. To achieve a better therapeutic effect and quality of survival, the combination of multiple treatment modalities presents great research value. Here we reviewed the interaction between PD-1/PD-L1 and PI3K/AKT/mTOR pathway in the progression and treatment of NSCLC and summarized its clinical implications. The intracellular interactions between PD-1/PD-L1 and the PI3K/AKT/mTOR pathway indicate that PD-1/PD-L1 inhibitors have a wide range of potential applications. And we presented the mechanism for combining therapy with monoclonal antibody PD-1/PD-L1 and PI3K/AKT/mTOR inhibitors in this review, to broaden the therapies for NSCLC.

show abstract

Section: Interaction Between Pi3k/akt/mtor Pathway and Pd-1/pd-l1mentioning

confidence: 99%

Clinical implications of the interaction between PD-1/PD-L1 and PI3K/AKT/mTOR pathway in progression and treatment of non-small cell lung cancer

Quan¹,

Yang²,

Zheng³

et al. 2022

J. Cancer

View full text Add to dashboard Cite

show abstract

“…Consistent with their higher abundance in CTE samples and negative logistic regression coefficients, both cluster 20 and 21 showed enrichment of several phenotypes describing the induction of Tregs. ERK2 is known to modulate PD-L1 expression and its inhibition has been shown to improve anti-PD-L1 blockade in several cancer types, including NSCLC ( Ng et al, 2018 ; Kumar et al, 2020 ; Henry et al, 2021 ; Luo et al, 2021 ). Conversely, while CK1 is associated with tumorigenesis, tumor growth, and drug resistance in cancer cells, its role in different immune cells and its ability to promote immune evasion has not been addressed.…”

Section: Resultsmentioning

confidence: 99%

Dual data and motif clustering improves the modeling and interpretation of phosphoproteomic data

Creixell

Meyer

2022

Cell Reports Methods

View full text Add to dashboard Cite

“…Culture. Human lung cancer cell lines A549, H358, H460, H1299, PC9, and SPC-A-1 and normal human lung epithelial cell BEAS-2B were purchased from American Type Culture Collection and cultured in DMEM medium supplemented with 10% fetal bovine serum (FBS) and 1% antibiotics at 37 °C under the humidified atmosphere [29][30][31]. The cells were preinfected for 12 h with lentiviral vectors carrying two different interfering sequences against TRIM6 at a multiplicity of infection (MOI) of 50 to silence endogenous TRIM6 or with TRIM6-OE virus (MOI = 20) to overexpress TRIM6.…”

Section: Cellmentioning

confidence: 99%

TRIM6 Reduces Ferroptosis and Chemosensitivity by Targeting SLC1A5 in Lung Cancer

Zhang

Dong

Liu

et al. 2023

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Objective. Ferroptosis, a newly identified form of cell death, plays critical roles in the development and chemoresistance of lung cancer. Tripartite motif 6 (TRIM6) acts as an E3-ubiquitin ligase and can promote the progression of human colorectal cancer. The present study is aimed at investigating its role and potential mechanisms in lung cancer. Methods. Lentiviral vectors were used to overexpress or knock down TRIM6 in human lung cancer cells. Cell survival, colony formation, lipid peroxidation, intracellular iron levels, and other ferroptotic markers were examined. The role of TRIM6 on ferroptosis and chemosensitivity was further tested in mouse tumor xenograft models. Results. TRIM6 was highly expressed in human lung cancer tissues and cells, and its expression in the lung cancer cells was further increased by ferroptotic stimulation. TRIM6 overexpression inhibited, while TRIM6 silence promoted erastin- and RSL3-induced glutaminolysis and ferroptosis in the lung cancer cells. Mechanistically, TRIM6 directly interacted with solute carrier family 1 member 5 to promote its ubiquitination and degradation, thereby inhibiting glutamine import, glutaminolysis, lipid peroxidation, and ferroptotic cell death. Moreover, we observed that TRIM6 overexpression reduced the chemotherapeutic effects of cisplatin and paclitaxel. In contrast, TRIM6 silence sensitized human lung cancer cells to cisplatin and paclitaxel in vivo and in vitro. Conclusion. Our findings for the first time define TRIM6 as a negative regulator of ferroptosis in the lung cancer cells, and TRIM6 overexpression enhances the resistance of human lung cancer cells to chemotherapeutic drugs. Overall, targeting TRIM6 may help to establish novel strategies to treat lung cancer.

show abstract

PD0325901, an ERK inhibitor, enhances the efficacy of PD-1 inhibitor in non-small cell lung carcinoma

Cited by 22 publications

References 66 publications

Clinical implications of the interaction between PD-1/PD-L1 and PI3K/AKT/mTOR pathway in progression and treatment of non-small cell lung cancer

Clinical implications of the interaction between PD-1/PD-L1 and PI3K/AKT/mTOR pathway in progression and treatment of non-small cell lung cancer

Dual data and motif clustering improves the modeling and interpretation of phosphoproteomic data

TRIM6 Reduces Ferroptosis and Chemosensitivity by Targeting SLC1A5 in Lung Cancer

Contact Info

Product

Resources

About