Osimertinib in EGFR-Mutated Lung Cancer: A Review of the Existing and Emerging Clinical Data

Lee, Chung-Shien; Milone, Matthew; Seetharamu, Nagashree

doi:10.2147/ott.s227032

Cited by 27 publications

(30 citation statements)

References 71 publications

(103 reference statements)

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“…EGFR is activated in four phases (7,(20)(21)(22) (Figure 2): 1) The ligand binds to the extracellular domain of EGFR; 2) Homodimerization or heterodimerization with ErbB-2, ErbB-3, and ErbB-4 (also known as HER-2, HER-3, and HER-4, respectively) occurs. ErbB-2 is the most common heterodimerization partners of EGFR; 3) Autophosphorylation of tyrosine residues in the cytoplasmic domain occurs; 4) The activation of the intracellular signaling pathway occurs, which regulates cell proliferation, migration, differentiation, and apoptosis.…”

Section: Activation Mechanism Of Egfr Signaling Pathwaymentioning

confidence: 99%

Mechanism of Lethal Skin Toxicities Induced by Epidermal Growth Factor Receptor Inhibitors and Related Treatment Strategies

Duan

et al. 2022

Front. Oncol.

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Epidermal growth factor receptor (EGFR) inhibitors are widely used to treat various types of cancers such as non-small cell lung cancer, head and neck cancer, breast cancer, pancreatic cancer. Adverse reactions such as skin toxicity, interstitial lung disease, hepatotoxicity, ocular toxicity, hypomagnesemia, stomatitis, and diarrhea may occur during treatment. Because the EGFR signaling pathway is important for maintaining normal physiological skin function. Adverse skin reactions occurred in up to 90% of cancer patients treated with EGFR inhibitors, including common skin toxicities (such as papulopustular exanthemas, paronychia, hair changes) and rare fatal skin toxicities (e.g., Stevens–Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis). This has led to the dose reduction or discontinuation of EGFR inhibitors in the treatment of cancer. Recently, progress has been made about research on the skin toxicity of EGFR inhibitors. Here, we summarize the mechanism of skin toxicity caused by EGFR inhibitors, measures to prevent severe fatal skin toxicity, and provide reference for medical staff how to give care and treatment after adverse skin reactions.

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Section: Activation Mechanism Of Egfr Signaling Pathwaymentioning

confidence: 99%

Mechanism of Lethal Skin Toxicities Induced by Epidermal Growth Factor Receptor Inhibitors and Related Treatment Strategies

Duan

et al. 2022

Front. Oncol.

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“…Herein, a sufficient challenge is higher range of adverse effects during combinate therapy. For example, in osimertinib plus savolitinib tests with patients with mutations in EGFR and MET genes, overall response rate was 30% and high grade adverse effects occurred in 57% [137][138][139]. Another targeted drug for lung cancer treatment complies neovascularization inhibitors, within multiple receptor inhibitors (e.g., sorafenib), small-molecule tropomyosin receptor kinase inhibitors and serine/threonine inhibitors or CDK inhibitors [135].…”

Section: Targeted Therapymentioning

confidence: 99%

Clinical Application Perspectives of Lung Cancers 3D Tumor Microenvironment Models for In Vitro Cultures

Wieleba

Wojas‐Krawczyk

Krawczyk

et al. 2022

IJMS

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Despite the enormous progress and development of modern therapies, lung cancer remains one of the most common causes of death among men and women. The key element in the development of new anti-cancer drugs is proper planning of the preclinical research phase. The most adequate basic research exemplary for cancer study are 3D tumor microenvironment in vitro models, which allow us to avoid the use of animal models and ensure replicable culture condition. However, the question tormenting the scientist is how to choose the best tool for tumor microenvironment research, especially for extremely heterogenous lung cancer cases. In the presented review we are focused to explain the key factors of lung cancer biology, its microenvironment, and clinical gaps related to different therapies. The review summarized the most important strategies for in vitro culture models mimicking the tumor–tumor microenvironmental interaction, as well as all advantages and disadvantages were depicted. This knowledge could facilitate the right decision to designate proper pre-clinical in vitro study, based on available analytical tools and technical capabilities, to obtain more reliable and personalized results for faster introduction them into the future clinical trials.

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“…Therefore, the NSCLC is treated based on the oncogene mutations [ 65 , 66 , 67 ]. Many EGFR inhibitors are available in the market to treat NSCLC with common mutations [ 9 , 10 , 11 , 12 , 13 , 14 , 68 ]. The EGFRex20ins mutation is considered an uncommon mutation and has also been acknowledged as a separate subclass of EGFR mutations [ 69 ].…”

Section: Expert Opinionmentioning

confidence: 99%

“…The overexpression of EGFR is implicated in the pathogenesis of human cancers, including NSCLC [ 8 ]. Many EGFR inhibitors are in clinical practice to treat NSCLC, for example, erlotinib [ 9 ], gefitinib [ 10 ], afatinib [ 11 , 12 ], dacomitinib [ 13 ], and osimertinib [ 14 ]. However, many types of mutations, including the EGFR exon 20 insertions (EGFRex20ins) mutation, have been reported in EGFR [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Discovery, Development, Inventions, and Patent Trends on Mobocertinib Succinate: The First-in-Class Oral Treatment for NSCLC with EGFR Exon 20 Insertions

Imran

Khan²,

Alshammari

et al. 2021

Biomedicines

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The majority of lung cancers are non-small-cell lung cancer (NSCLC) having a low survival rate. Recent studies have indicated the involvement of epidermal growth factor receptor (EGFR) oncogene mutations like EGFR exon 20 insertions (EGFRex20ins) mutation among NSCLC patients. The response of patients of NSCLC with the EGFRex20ins mutation to the currently available EGFR inhibitor is negligible. Mobocertinib is the first oral treatment that has been approved by the USFDA, on 15 September 2021, to treat NSCLC with the EGFRex20ins mutation. This patent review discusses the inventions and patent literature of mobocertinib that will help the scientific community to develop additional and improved inventions related to mobocertinib. The structure of mobocertinib was first reported in 2015. Therefore, this article covered the patents/patent applications related to mobocertinib from 2015 to 25 October 2021. The patent search revealed 27 patents/patent applications related to compound, method of treatment, salt, polymorph, process, composition, and drug combinations of mobocertinib. The authors foresee an exciting prospect for developing a treatment for NSCLC with EGFRex20ins mutation, and other cancers employing a combination of mobocertinib with other approved anticancer agents. The inventions related to novel dosage forms, processes, and intermediates used in the synthesis of mobocertinib are also anticipated.

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Osimertinib in EGFR-Mutated Lung Cancer: A Review of the Existing and Emerging Clinical Data

Cited by 27 publications

References 71 publications

Mechanism of Lethal Skin Toxicities Induced by Epidermal Growth Factor Receptor Inhibitors and Related Treatment Strategies

Mechanism of Lethal Skin Toxicities Induced by Epidermal Growth Factor Receptor Inhibitors and Related Treatment Strategies

Clinical Application Perspectives of Lung Cancers 3D Tumor Microenvironment Models for In Vitro Cultures

Discovery, Development, Inventions, and Patent Trends on Mobocertinib Succinate: The First-in-Class Oral Treatment for NSCLC with EGFR Exon 20 Insertions

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