Epidermal Growth Factor Receptor Expression and Resistance Patterns to Targeted Therapy in Non-Small Cell Lung Cancer: A Review

Karlsen, Emma; Kahler, Sam L.; Tefay, Joan; Joseph, Shannon R.; Simpson, Fiona

doi:10.3390/cells10051206

Cited by 22 publications

(20 citation statements)

References 229 publications

(203 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to data by the World Health Organization, lung cancer was the most common cause of cancer-related death worldwide in 2020, with 1.80 million deaths (WHO, 2021). Non-small-cell lung cancer (NSCLC), which accounts for approximately 85% of lung cancer diagnoses globally, has been classified by WHO as a heterogenous group comprising mainly adenocarcinomas and squamous cell carcinomas [ 1 ]. Physical, chemical and biological carcinogens are thought to be responsible for lung cancer development, with tobacco smoking being the most prevalent (World Health Organization, 2021).…”

Section: Introductionmentioning

confidence: 99%

Resistance to TKIs in EGFR-Mutated Non-Small Cell Lung Cancer: From Mechanisms to New Therapeutic Strategies

Koulouris

Tsagkaris

Corriero

et al. 2022

Cancers

View full text Add to dashboard Cite

Resistance to tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) in advanced mutant Non-Small Cell Lung Cancer (NSCLC) constitutes a therapeutic challenge. This review intends to summarize the existing knowledge about the mechanisms of resistance to TKIs in the context of EGFR mutant NSCLC and discuss its clinical and therapeutic implications. EGFR-dependent and independent molecular pathways have the potential to overcome or circumvent the activity of EGFR-targeted agents including the third-generation TKI, osimertinib, negatively impacting clinical outcomes. CNS metastases occur frequently in patients on EGFR-TKIs, due to the inability of first and second-generation agents to overcome both the BBB and the acquired resistance of cancer cells in the CNS. Newer-generation TKIs, TKIs targeting EGFR-independent resistance mechanisms, bispecific antibodies and antibody-drug conjugates or combinations of TKIs with other TKIs or chemotherapy, immunotherapy and Anti–Vascular Endothelial Growth Factors (anti-VEGFs) are currently in use or under investigation in EGFR mutant NSCLC. Liquid biopsies detecting mutant cell-free DNA (cfDNA) provide a window of opportunity to attack mutant clones before they become clinically apparent. Overall, EGFR TKIs-resistant NSCLC constitutes a multifaceted therapeutic challenge. Mapping its underlying mutational landscape, accelerating the detection of resistance mechanisms and diversifying treatment strategies are essential for the management of the disease.

show abstract

Section: Introductionmentioning

confidence: 99%

Resistance to TKIs in EGFR-Mutated Non-Small Cell Lung Cancer: From Mechanisms to New Therapeutic Strategies

Koulouris

Tsagkaris

Corriero

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“…While such EGFR-TKIs can significantly improve the life quality and the median survival rate of patients and show better performance in terms of progression-free survival rate or objective response rate, such therapeutics also suffer problems such as drug resistance after a period of administration ( Spaans and Goss, 2014 ; Karlsen et al, 2021 ; Zhao et al, 2021 ), and developing new EGFR-TK targeting chemical entities with reduced drug resistance but similar antitumor activity is highly desirable ( Zhang et al, 2014 ; Maione et al, 2015 ; Tsubata et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Antitumor Activity of Erlotinib Derivatives

Mao

Wang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Nineteen erlotinib derivatives bearing different 1,2,3-triazole moieties were designed, synthesized, and evaluated for their potential against different cancer cell lines. The structures of the synthesized compounds were confirmed via1H NMR, 13C NMR, and HR MS. Preliminary antitumor activity assay results suggested that some compounds showed remarkable inhibitory activity against different cancer cell lines including the corresponding drug-resistant ones. Among these compounds, 3d was the most promising one with an IC50 of 7.17 ± 0.73 μM (KYSE70TR), 7.91 ± 0.61 μM (KYSE410TR), 10.02 ± 0.75 μM (KYSE450TR), 5.76 ± 0.3 3 μM (H1650TR), and 2.38 ± 0.17 μM (HCC827GR). A preliminary mechanism study suggested that compound 3d suppressed cancer cell proliferation through the EGFR-TK pathway.

show abstract

“…A second class of mAb, the so-called ‘immune checkpoint inhibitors’, such as Ipilimumab and Nivolumab, instead target and modify the anti-cancer effector functions of immune cells, most notably cytotoxic T lymphocytes [ 16 , 17 ]. Although both types of mAbs can be effective at suppressing or even eliminating large, established tumors, a significant fraction of patients fail to respond to treatment or develop resistance [ 18 , 19 , 20 ]. An improved understanding of the mechanisms underlying resistance to treatment is needed for the rational development of novel therapeutics that could augment the efficacy of existing tumor-targeting mAbs.…”

Section: Introductionmentioning

confidence: 99%

Remodeling the Tumor Myeloid Landscape to Enhance Antitumor Antibody Immunotherapies

Hussain

Cragg

Beers

2021

Cancers

View full text Add to dashboard Cite

Among the diverse tumor resident immune cell types, tumor-associated macrophages (TAMs) are often the most abundant, possess an anti-inflammatory phenotype, orchestrate tumor immune evasion and are frequently associated with poor prognosis. However, TAMs can also be harnessed to destroy antibody-opsonized tumor cells through the process of antibody-dependent cellular phagocytosis (ADCP). Clinically important tumor-targeting monoclonal antibodies (mAb) such as Rituximab, Herceptin and Cetuximab, function, at least in part, by inducing macrophages to eliminate tumor cells via ADCP. For IgG mAb, this is mediated by antibody-binding activating Fc gamma receptors (FcγR), with resultant phagocytic activity impacted by the level of co-engagement with the single inhibitory FcγRIIb. Approaches to enhance ADCP in the tumor microenvironment include the repolarization of TAMs to proinflammatory phenotypes or the direct augmentation of ADCP by targeting so-called ‘phagocytosis checkpoints’. Here we review the most promising new strategies targeting the cell surface molecules present on TAMs, which include the inhibition of ‘don’t eat me signals’ or targeting immunostimulatory pathways with agonistic mAb and small molecules to augment tumor-targeting mAb immunotherapies and overcome therapeutic resistance.

show abstract

Epidermal Growth Factor Receptor Expression and Resistance Patterns to Targeted Therapy in Non-Small Cell Lung Cancer: A Review

Cited by 22 publications

References 229 publications

Resistance to TKIs in EGFR-Mutated Non-Small Cell Lung Cancer: From Mechanisms to New Therapeutic Strategies

Resistance to TKIs in EGFR-Mutated Non-Small Cell Lung Cancer: From Mechanisms to New Therapeutic Strategies

Design, Synthesis, and Antitumor Activity of Erlotinib Derivatives

Remodeling the Tumor Myeloid Landscape to Enhance Antitumor Antibody Immunotherapies

Contact Info

Product

Resources

About