Tumor immune microenvironment in epidermal growth factor receptor-mutated non-small cell lung cancer before and after epidermal growth factor receptor tyrosine kinase inhibitor treatment: a narrative review

Liu, L.; Wang, Chao; Li, Sini; Bai, Hua; Wang, Jie

doi:10.21037/tlcr-21-572

Cited by 36 publications

(34 citation statements)

References 145 publications

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“…The enrichment in the extracellular organization pathway, attributed to stromal cells (17), confirms stromal infiltration into the TME for patients resistant to EGFR TKI treatment. Previous studies showed that activation of PD-1 signaling, indicative of immunosuppression, and the PI3K/AKT pathway correlates with EGFR TKI resistance (18), consistent with our observation of increased tumor-stroma interaction in the predicted-not-to benefit group.…”

Section: Tme Image Features Predict Egfr Tki Survival Benefitsupporting

confidence: 92%

Features of tumor-microenvironment images predict targeted therapy survival benefit in patients with EGFR-mutant lung cancer

Wang¹,

Rong²,

Yang³

et al. 2023

Journal of Clinical Investigation

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travel and lodging and food and beverage have been provided by AstraZeneca, Pfizer, Regeneron, and Genentech to MGK. MGK is an employee of Memorial Sloan Kettering (MSK). MSK has received research funding from the National Cancer Institute (USA), the Lung Cancer Research Foundation, Genentech Roche, and PUMA Biotechnology for research conducted by MGK. MSK has licensed testing for EGFR T790M to MolecularMD. LS reports consulting fees from AstraZeneca, Foghorn Therapeutics, and EMD Serono; she has received honoraria for participation in educational programs from Physicians Education Resources, Peerview, and Paradigm Medical Communications. LS reports research funding to her institution (Brigham and Women's Hospital) from Roche/Genentech. DJK reports research grant support from Genentech, Revolution Medicines, and AADI and is a consultant to Bridgebio and Guidepoint. GX and YX are cofounders of Adjuvant Genomics Inc. JDM receives royalties from the NCI and UTSW for distribution of cell lines.

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Section: Tme Image Features Predict Egfr Tki Survival Benefitsupporting

confidence: 92%

Features of tumor-microenvironment images predict targeted therapy survival benefit in patients with EGFR-mutant lung cancer

Wang¹,

Rong²,

Yang³

et al. 2023

Journal of Clinical Investigation

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“…EMT is emerging as a crucial target for anticancer therapy in combination with the agents eradicating tumor bulk. 44 In sum, this study suggests that melatonin treatment suppressed the growth of NSCLC cells and induced apoptosis. Mechanistic studies indicated that hsa_circ_0017109 was significantly underexpressed in melatonin-treated cells.…”

Section: Discussionmentioning

confidence: 59%

“…Jiang et al 43 summarized that the Hippo pathway is involved in carcinogenesis and progression of NSCLC and SCLC, and high expression levels of YAP and TAZ are independent and novel prognostic factors for lung cancer. EMT is emerging as a crucial target for anticancer therapy in combination with the agents eradicating tumor bulk 44 …”

Section: Discussionmentioning

confidence: 99%

Melatonin may suppress lung adenocarcinoma progression via regulation of the circular noncoding RNA hsa_circ_0017109/miR‐135b‐3p/TOX3 axis

Wang¹,

Wang²,

Shao³

et al. 2022

Journal of Pineal Research

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Melatonin is a hormone synthesized in the pineal gland and has widespread physiological and pharmacological functions. Moreover, it can activate protective receptor-dependent processes. These processes can prevent tissue carcinogenesis and inhibit malignant tumor progression and metastasis. Therefore, we investigated the regulatory effects of melatonin on dysregulated circular RNAs in human lung adenocarcinoma (LUAD) cells. In this study, we treated LUAD cells with melatonin and measured the expression of hsa_circ_0017109, miR-135b-3p, and TOX3 by quantitative reverse transcription polymerase chain reaction. Colony formation and cell counting kit-8 assays were used to determine cell proliferation. The wound-healing assay and Transwell experiment were carried out to evaluate the migration potential and invasive capacity of LUAD cells. Also, cell apoptosis was detected using a cell apoptosis kit, and protein production was identified by Western blot. It was suggested that melatonin could inhibit LUAD progression in vivo and in vitro, and the role of TOX3 in this process was explored. Additionally, hsa_circ_0017109 was found to sponge miR-135b-3p, a downstream factor of circ_0017109, which was demonstrated to target TOX3 in LUAD cells and could promote the Hippo pathway and epithelial-mesenchymal transition

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“…Four of the hallmarks of NSCLC tumors are a potential immune-suppressive microenvironment and erratic (and potential inadequate) neovascularization and perfusion caused by changes in the microenvironment [ 39 , 40 , 49 ] resulting in decrease in pH of the tumor microenvironment [ 41 ]. We hypothesized that either of these hallmarks could predict a decreased cellular concentration of the TKIs, even at a high affinity and higher expression of EGFR in the tumor.…”

Section: Methodsmentioning

confidence: 99%

Physiologically Based Pharmacokinetic (PBPK) Modeling to Predict PET Image Quality of Three Generations EGFR TKI in Advanced-Stage NSCLC Patients

et al. 2022

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Introduction: Epidermal growth factor receptor (EGFR) mutated NSCLC is best treated using an EGFR tyrosine kinase inhibitor (TKI). The presence and accessibility of EGFR overexpression and mutation in NSCLC can be determined using radiolabeled EGFR TKI PET/CT. However, recent research has shown a significant difference between image qualities (i.e., tumor-to-lung contrast) in three generation EGFR TKIs: 11C-erlotinib, 18F-afatinib and 11C-osimertinib. In this research we aim to develop a physiological pharmacokinetic (PBPK)-model to predict tumor-to-lung contrast and as a secondary outcome the uptake of healthy tissue of the three tracers. Methods: Relevant physicochemical and drug specific properties (e.g., pKa, lipophilicity, target binding) for each TKI were collected and applied in established base PBPK models. Key hallmarks of NSCLC include: immune tumor deprivation, unaltered tumor perfusion and an acidic tumor environment. Model accuracy was demonstrated by calculating the prediction error (PE) between predicted tissue-to-blood ratios (TBR) and measured PET-image-derived TBR. Sensitivity analysis was performed by excluding each key component and comparing the PE with the final mechanistical PBPK model predictions. Results: The developed PBPK models were able to predict tumor-to-lung contrast for all EGFR-TKIs within threefold of observed PET image ratios (PE tumor-to-lung ratio of −90%, +44% and −6.3% for erlotinib, afatinib and osimertinib, respectively). Furthermore, the models depicted agreeable whole-body distribution, showing high tissue distribution for osimertinib and afatinib and low tissue distribution at high blood concentrations for erlotinib (mean PE, of −10.5%, range −158%–+190%, for all tissues). Conclusion: The developed PBPK models adequately predicted the image quality of afatinib and osimertinib and erlotinib. Some deviations in predicted whole-body TBR lead to new hypotheses, such as increased affinity for mutated EGFR and active influx transport (erlotinib into excreting tissues) or active efflux (afatinib from brain), which is currently unaccounted for. In the future, PBPK models may be used to predict the image quality of new tracers.

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Tumor immune microenvironment in epidermal growth factor receptor-mutated non-small cell lung cancer before and after epidermal growth factor receptor tyrosine kinase inhibitor treatment: a narrative review

Cited by 36 publications

References 145 publications

Features of tumor-microenvironment images predict targeted therapy survival benefit in patients with EGFR-mutant lung cancer

Features of tumor-microenvironment images predict targeted therapy survival benefit in patients with EGFR-mutant lung cancer

Melatonin may suppress lung adenocarcinoma progression via regulation of the circular noncoding RNA hsa_circ_0017109/miR‐135b‐3p/TOX3 axis

Physiologically Based Pharmacokinetic (PBPK) Modeling to Predict PET Image Quality of Three Generations EGFR TKI in Advanced-Stage NSCLC Patients

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