The epidermal growth factor receptor (EGFR) signaling is aberrantly overexpressed in many solid malignancies, making it an important target for anti-cancer biologic agents. Among them, epidermal growth factor receptor inhibitors (EGFRIs), which have been widely used in clinical practice, include anti-EGFR monoclonal antibodies and tyrosine kinase inhibitors. A proportion of patients treated with EGFRIs develop specific, dose-dependent skin toxicity such as papulopustular rash, paronychia, xerosis and itch. These side effects can cause physical and psychosocial discomfort that may result in dose reduction, discontinuance, or replacement of the current EGFRIs treatment. Correct diagnosis and treatment of these skin and mucosal adverse effects associated with EGFRIs is of great significance for the tertiary prevention of malignant tumors. A review on EGFRI-related mucocutaneous adverse reactions is presented here, focusing on the pathogenesis, the various clinical manifestations, the strategies for prevention and treatment of these conditions.
Antibodies, Monoclonal/adverse effects* ; Antineoplastic Agents/therapeutic use* ; ErbB Receptors/therapeutic use* ; Humans ; Neoplasms/drug therapy* ; Protein Kinase Inhibitors/therapeutic use*

Antineoplastic Agents ; therapeutic use ; Aromatase Inhibitors ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Female ; Humans ; Neoadjuvant Therapy ; Neoplasm Staging ; Nitriles ; therapeutic use ; Postmenopause ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Remission Induction ; Triazoles ; therapeutic use

OBJECTIVE: To analyze the influence of serum levels of transforming growth factor-β1 (TGF-β1) and epidermal growth factor receptor (EGFR) on the therapeutic effect of high-dose cytarabine (HD-AraC) in patients with acute myeloid leukemia (AML). METHODS: 98 patients with AML treated in our hospital from January 2019 to June 2020 were selected as the research subjects, all patients were treated with HD-AraC for 1 course of treatment every week. The effect of 2 groups were evaluated during after one course of treatment and divided into effective group and ineffective group, statistical table of baseline data was designed, the baseline data of 2 groups were counted in detail, the baseline data and serum levels of TGF-β1 and EGFR of 2 groups were compared, Logistic regression analysis was used to examine the relationship between the levels of serum TGF-β1, EGFR and the therapeutic effect of HD-AraC in patients with AML, the value of serum TGF-β1 and EGFR levels in predicting the therapeutic effect of HD-AraC in AML patients was analyzed based on ROC curve and decision curve. RESULTS: After 1 course of treatment, among the 98 patients, 26 cases had complete remission, 38 cases had partially remission and 34 cases no remission, the total effective rate was 65.31% (64/98); after comparing data of 2 groups, Logistic regression analysis showed that the overexpression of serum EGFR before treatment might be a risk factor for the ineffective treatment of HD-AraC in AML patients (OR>1, P<0.05), overexpression of serum TGF-β1 before treatment might be a protective factor for the ineffective treatment of HD-AraC in AML patients (OR<1, P<0.05); the ROC curve results showed that the AUC of serum EGFR and TGF-β1 before treatment in predicting the risk of ineffective HD-AraC treatment in AML patients were >0.70, which had certain predictive value. The decision curve results showed that in the threshold range of 0.15-044, the prediction model combined with serum EGFR and TGF-β1 levels in predicting the net benefit rate of HD-AraC treatment in AML patients was better than that of serum EGFR or serum TGF-β1 alone. CONCLUSION The levels of serum TGF-β1 and EGFR affect the therapeutic effect of HD-AraC in patients with AML and increase the risk of ineffective treatment, serum TGF-β1 and EGFR can be used to predict the risk of ineffective HD-AraC treatment in AML patients, and the combined prediction of net benefit rate is higher.
Cytarabine/therapeutic use* ; ErbB Receptors/blood* ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Remission Induction ; Transforming Growth Factor beta1/blood*

OBJECTIVES: To investigate the effects of PLK1 inhibitors on osimertinib-resistant non-small cell lung carcinoma (NSCLC) cells and the anti-tumor effect combined with osimertinib. METHODS: An osimertinib resistant NCI-H1975 cell line was induced by exposure to gradually increasing drug concentrations. Osimertinib-resistant cells were co-treated with compounds from classical tumor pathway inhibitor library and osimertinib to screen for compounds with synergistic effects with osimertinib. The Gene Set Enrichment Analysis (GSEA) was used to investigate the activated signaling pathways in osimertinib-resistant cells; sulforhodamine B (SRB) staining was used to investigate the effect of PLK1 inhibitors on osimertinib-resistant cells and the synergistic effect of PLK1 inhibitors combined with osimertinib. RESULTS: Osimertinib-resistance in NCI-H1975 cell (resistance index=43.45) was successfully established. The PLK1 inhibitors GSK 461364 and BI 2536 had synergistic effect with osimertinib. Compared with osimertinib-sensitive cells, PLK1 regulatory pathway and cell cycle pathway were significantly activated in osimertinib-resistant cells. In NSCLC patients with epidermal growth factor receptor mutations treated with osimertinib, PLK1 mRNA levels were negatively correlated with progression free survival of patients (R=－0.62, P<0.05), indicating that excessive activation of PLK1 in NSCLC cells may cause cell resistant to osimertinib. Further in vitro experiments showed that IC₅₀ of PLK1 inhibitors BI 6727 and GSK 461364 in osimertinib-resistant cells were lower than those in sensitive ones. Compared with the mono treatment of osimertinib, PLK1 inhibitors combined with osimertinib behaved significantly stronger effect on the proliferation of osimertinib-resistant cells. CONCLUSIONS PLK1 inhibitors have a synergistic effect with osimertinib on osimertinib-resistant NSCLC cells which indicates that they may have potential clinical value in the treatment of NSCLC patients with osimertinib resistance.
Humans ; Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms ; ErbB Receptors/therapeutic use* ; Drug Resistance, Neoplasm/genetics* ; Mutation ; Cell Line, Tumor

Carcinoma, Non-Small-Cell Lung/genetics* ; Consensus ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use*

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are often associated with non-EGFR genetic alterations, which may be a reason for the poor efficacy of EGFR tyrosine kinase inhibitors (TKIs). Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations. METHODS: Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant non-EGFR genetic alterations were retrospectively collected. And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy. Demographic, clinical and pathological data were collected, and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression. Survival data were obtained through face-to-face or telephone follow-up. The differences between the two groups in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were investigated. RESULTS 107 patients were included, including 63 cases in the combination group and 44 cases in the monotherapy group. The ORR were 78% and 50% (P=0.003), and DCR were 97% and 77% (P=0.002), respectively. At a median follow-up of 13.7 mon, a PFS event occurred in 38.1% and 81.8% of patients in the two groups, with median PFS of 18.8 mon and 5.3 mon, respectively (P<0.000,1). Median OS was unreached in the combination group, and 27.8 mon in the monotherapy group (P=0.31). According to the Cox multivariate regression analysis, combination therapy was an independent prognostic factor of PFS CONCLUSIONS: In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations, combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy, which should be the preferred treatment option.
Adenocarcinoma of Lung/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/pathology* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Retrospective Studies

A significant clinical challenge in lung cancer treatment is management of the inevitable acquired resistance to third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs), such as osimertinib, which have shown remarkable success in the treatment of advanced NSCLC with EGFR activating mutations, in order to achieve maximal response duration or treatment remission. Apoptosis is a major type of programmed cell death tightly associated with cancer development and treatment. Evasion of apoptosis is considered a key hallmark of cancer and acquisition of apoptosis resistance is accordingly a key mechanism of drug acquired resistance in cancer therapy. It has been clearly shown that effective induction of apoptosis is a key mechanism for third generation EGFR-TKIs, particularly osimertinib, to exert their therapeutic efficacies and the development of resistance to apoptosis is tightly associated with the emergence of acquired resistance. Hence, restoration of cell sensitivity to undergo apoptosis using various means promises an effective strategy for the management of acquired resistance to third generation EGFR-TKIs.
Humans ; Drug Resistance, Neoplasm/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; ErbB Receptors ; Lung Neoplasms/genetics* ; Apoptosis

Clinical studies have established the clinical application of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) adjuvant targeted therapy. Compared with chemotherapy, the high efficiency and low toxicity of targeted therapy increases the survival benefit of patients. Icotinib was the first EGFR-TKI with independent intellectual property rights in China and the third EGFR-TKI to be marketed in the world. In order to summarize the experience of icotinib and other EGFR-TKIs in the adjuvant treatment of non-small cell lung cancer and further standardize and guide the clinical application of icotinib, experts from the China International Exchange and Promotive Association for Medical and Health Care and the Guangdong Association of Thoracic Diseases have organized an expert consensus on the adjuvant treatment of non-small cell lung cancer with icotinib, which is expected to provide clinicians with evidence-based medical evidences for postoperative targeted drug using.
Humans ; Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms/surgery* ; Consensus ; Mutation ; ErbB Receptors/genetics* ; Crown Ethers/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) targeting EGFR are effective in EGFR mutation-positive non-small cell lung cancer (NSCLC) patients, but drug resistance is inevitable. With the application and expansion of individualized and combined therapy, more and more studies have shown that combined administration of Metformin effectively solves the problem of acquired drug resistance to EGFR-TKIs in clinical treatment and prolongs the survival of patients with NSCLC. EGFR-TKIs combined with Metformin is expected to be the treatment method of choice for NSCLC patients with EGFR-TKIs resistance. This paper intends to summarize the research progress of EGFR-TKIs combined with Metformin in the treatment of EGFR-TKIs acquired resistance in NSCLC, in order to provide a new idea for the treatment of NSCLC patients with acquired resistance to EGFR-TKIs.
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Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Metformin/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use* ; ErbB Receptors/metabolism* ; Drug Resistance, Neoplasm ; Mutation

Lung cancer is one of the leading causes of cancer-related morbidity and mortality. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) have become the standard treatment for EGFR-mutated advanced non-small cell lung cancer (NSCLC). Unfortunately, drug resistance is inevitable in most cases. EGFR-TKI combined with angiogenesis inhibitors is a treatment scheme being explored to delay the therapeutic resistance, which is called "A+T treatment". Several clinical trials have demonstrated that the A+T treatment can improve the progression free survival (PFS) of the NSCLC patients. However, compared to EGFR-TKI monotherapy, the benefits of the A+T treatment based on different EGFR-TKIs, as well as its safety and exploration prospects are still unclear. Therefore, we reviewed the literature related to all three generations EGFR-TKIs combined with angiogenesis inhibitors, and summarized the mechanism, benefit, safety, optimal target population of A+T treatment.
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Angiogenesis Inhibitors/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use*