Progress in Treatment of Non-Small Cell Lung Cancer Harboring HER2 Aberrations

Ni, Jun; Zhang, Li

doi:10.2147/ott.s312820

Cited by 8 publications

(13 citation statements)

References 86 publications

(168 reference statements)

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“…Hence, the HER2 expression level can be considered as a target for cancer prognosis and diagnosis. HER2-based treatment strategies involve either the direct targeting of HER2 or related signaling pathways [ 118 , 119 ]. However, an aberrant form of HER2, known as p95, which has no extracellular domain, leads to therapeutic resistance and highlights the urgent need for more effective therapies [ 120 ].…”

Section: Established Targets For Car Nk Cellsmentioning

confidence: 99%

NK Cells Armed with Chimeric Antigen Receptors (CAR): Roadblocks to Successful Development

Dezfouli

Yazdi

Pockley

et al. 2021

Cells

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In recent years, cell-based immunotherapies have demonstrated promising results in the treatment of cancer. Chimeric antigen receptors (CARs) arm effector cells with a weapon for targeting tumor antigens, licensing engineered cells to recognize and kill cancer cells. The quality of the CAR-antigen interaction strongly depends on the selected tumor antigen and its expression density on cancer cells. CD19 CAR-engineered T cells approved by the Food and Drug Administration have been most frequently applied in the treatment of hematological malignancies. Clinical challenges in their application primarily include cytokine release syndrome, neurological symptoms, severe inflammatory responses, and/or other off-target effects most likely mediated by cytotoxic T cells. As a consequence, there remains a significant medical need for more potent technology platforms leveraging cell-based approaches with enhanced safety profiles. A promising population that has been advanced is the natural killer (NK) cell, which can also be engineered with CARs. NK cells which belong to the innate arm of the immune system recognize and kill virally infected cells as well as (stressed) cancer cells in a major histocompatibility complex I independent manner. NK cells play an important role in the host’s immune defense against cancer due to their specialized lytic mechanisms which include death receptor (i.e., Fas)/death receptor ligand (i.e., Fas ligand) and granzyme B/perforin-mediated apoptosis, and antibody-dependent cellular cytotoxicity, as well as their immunoregulatory potential via cytokine/chemokine release. To develop and implement a highly effective CAR NK cell-based therapy with low side effects, the following three principles which are specifically addressed in this review have to be considered: unique target selection, well-designed CAR, and optimized gene delivery.

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Section: Established Targets For Car Nk Cellsmentioning

confidence: 99%

NK Cells Armed with Chimeric Antigen Receptors (CAR): Roadblocks to Successful Development

Dezfouli

Yazdi

Pockley

et al. 2021

Cells

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“…HER2 is coded by the gene ERBB2, a transmembrane tyrosine kinase which undergoes homodimerization or heterodimerization after ligand binding and subsequently activates the RAS-MAPK and the PI3K-AKT-mTOR pathways. These pathways are involved in cell survival, proliferation and apoptosis [6,15]. Insertions and deletion in exon 20 of HER2 are found in 2-4% of newly diagnosed NSCLC and are more common in Asian, nonsmoking and female patients [6,16].…”

Section: Human Epidermal Growth Factor Receptormentioning

confidence: 99%

“…Several novel HER2 inhibitors, as pyrotinib, poziotinib, lapatinib, dacomitinib and neratinib are currently under evaluation for their activity in HER2 mutated NSCLC and have shown some encouraging results [6,15]. mAbs against HER2 are widely and successfully used in HER2-positive breast cancer, but the results in NSCLC are by far not as convincing.…”

Section: Human Epidermal Growth Factor Receptormentioning

confidence: 99%

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Rare driver alterations in nonsmall cell lung cancer: novel targeted drugs

Kauffmann-Guerrero¹,

Tufman²

2021

Current Opinion in Oncology

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Purpose of reviewThe current review presents clinically relevant driver alterations in nonsmall cell lung cancer (NSCLC) and the targeted treatments currently available for clinical use as well as those in clinical trials and advanced stages of drug development. Recent findingsMesenchymal-epithelial transition factor, human epidermal growth factor receptor 2, proto-oncogene B-RAF (BRAF), proto-oncogene tyrosine-protein kinase ROS (ROS1), rearranged during transfection (RET) and neurotrophic tyrosine kinase are rare genetic driver alterations, each present in a small subset of patients with NSCLC. Treatments targeting BRAF, ROS1, RET and neurotrophic tyrosine kinase are approved in Europe, and promising treatments targeting mesenchymal-epithelial transition factor and human epidermal growth factor receptor 2 are available in clinical trials and compassionate use programs. The response rates, duration of response and tolerability observed in trials of targeted drugs in this setting are presented in detail here.

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“…The global lung cancer occurrence could be due to outdoor ambient PM2.5 and tobacco ( Guo et al, 2020 ; Turner et al, 2020 ; Frazer et al, 2022 ). Multiple gene mutations have been found in NSCLC patient, including epidermal growth factor receptor (EGFR) ( Zhao D. et al, 2022 ; Castaneda-Gonzalez et al, 2022 ), Kirsten rat sarcoma viral oncogene homolog (KRAS) ( Desage et al, 2022 ; Garcia-Robledo et al, 2022 ), anaplastic lymphoma kinase (ALK) ( Cognigni et al, 2022 ; Xiang et al, 2022 ), Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2) ( Ni and Zhang, 2021 ; Vathiotis et al, 2021 ; Yu X. et al, 2022 ), B-Raf proto-oncogene (BRAF) ( Abdayem and Planchard, 2022 ; Riudavets et al, 2022 ; Sforza et al, 2022 ), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), AKT serine/threonine kinase 1 (AKT1), mitogen-activated protein kinase kinase 1 (MAP2K1) ( Kim and Giaccone, 2018 ; Han et al, 2021 ), c-ros oncogene 1 (ROS1) ( Guaitoli et al, 2021 ; Yu Z. Q. et al, 2022 ), neurotrophic tyrosine receptor kinase (NTRK) ( Liu C. et al, 2022 ; Qin and Patel, 2022 ), and mesenchymal-epithelial transition factor (MET) ( Pao and Girard, 2011 ; Olmedo et al, 2022 ) ( Figure 1 ). In SCLC patients, gene mutations often include retinoblastoma (Rb), TP53, PTEN, FBXW7, VHL mutations ( Cardona et al, 2019 ; Guan et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Targeting immune cell types of tumor microenvironment to overcome resistance to PD-1/PD-L1 blockade in lung cancer

Wang

Zhu²,

Yang³

et al. 2023

Front. Pharmacol.

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Lung cancer is the common malignant tumor with the highest mortality rate. Lung cancer patients have achieved benefits from immunotherapy, including immune checkpoint inhibitors (ICIs) therapy. Unfortunately, cancer patients acquire adaptive immune resistance, leading to poor prognosis. Tumor microenvironment (TME) has been demonstrated to play a critical role in participating in acquired adaptive immune resistance. TME is associated with molecular heterogeneity of immunotherapy efficacy in lung cancer. In this article, we discuss how immune cell types of TME are correlated with immunotherapy in lung cancer. Moreover, we describe the efficacy of immunotherapy in driven gene mutations in lung cancer, including KRAS, TP53, EGFR, ALK, ROS1, KEAP1, ZFHX3, PTCH1, PAK7, UBE3A, TNF-α, NOTCH, LRP1B, FBXW7, and STK11. We also emphasize that modulation of immune cell types of TME could be a promising strategy for improving adaptive immune resistance in lung cancer.

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Progress in Treatment of Non-Small Cell Lung Cancer Harboring HER2 Aberrations

Cited by 8 publications

References 86 publications

NK Cells Armed with Chimeric Antigen Receptors (CAR): Roadblocks to Successful Development

NK Cells Armed with Chimeric Antigen Receptors (CAR): Roadblocks to Successful Development

Rare driver alterations in nonsmall cell lung cancer: novel targeted drugs

Targeting immune cell types of tumor microenvironment to overcome resistance to PD-1/PD-L1 blockade in lung cancer

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