Update on recent preclinical and clinical studies of T790M mutant-specific irreversible epidermal growth factor receptor tyrosine kinase inhibitors

Liao, Bin-Chi; Lin, Chia‐Chi; Lee, Jih‐Hsiang; Yang, James Chih‐Hsin

doi:10.1186/s12929-016-0305-9

Cited by 42 publications

(24 citation statements)

References 79 publications

(88 reference statements)

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“…This is the case of patients with EGFR mutations, EML4-ALK rearrangement or ROS1 fusions (64). For instance, ertenolib, gefitinib and afatinib are used in the treatment of locally advanced or metastatic tumors with EGFR exon 19 deletion or exon 21 mutations, while osimertinib, olmutinib and osimertinib are employed in the case of EGFR T790M mutations (106)(107)(108)(109)(110)(111)(112). Crizotinib, ceritinib and alectinib in turn are used in similar tumors, which in this case show ALK alterations.…”

Section: Genome-guided Therapymentioning

confidence: 99%

Lung adenocarcinoma: from molecular basis to genome-guided therapy and immunotherapy

et al. 2017

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Although adenocarcinoma (ADC) is the most frequent lung cancer, its diagnosis is often late, when the local invasion is important and/or the metastases have already appeared. Therefore, the mortality at 5 years is still very high, ranging from 51% to 99%, depending on the stage. The implementation of different molecular techniques has allowed genomic studies even in relatively small histological samples such as obtained with non-invasive or minimally invasive techniques, facilitating a better phenotyping of lung ADC. Thus, current classification differentiates between preinvasive lesions (atypical adenomatous hyperplasia and in situ ADC), minimally invasive ADC (MIA) and invasive ADC. 'Field cancerization' is a concept that refers to progressive loco-regional changes occurring in tissues exposed to carcinogens, due to the interaction of the latter with a predisposing genetic background and an appropriate tissue microenvironment. Somatic genetic alterations, including mutations but also other changes, are necessary for oncogenesis, being especially frequent in lung ADC. Changes in the epidermal growth factor receptor () gene, Kirsten rat sarcoma viral oncogene (), v-Raf murine sarcoma viral oncogene homolog B (), gene encoding neurofibromin (), anaplastic lymphoma kinase () and are the main genes that suffer alterations in the tumors of patients with ADC. Molecular profiling of these tumors allows more targeted treatments through two distinct strategies, genome-guided therapy and immunotherapy. The former, targets the aberrant pathways secondary to the genomic alteration, whereas the latter may be based on the administration of antibodies [such as those against cytotoxic T-lymphocyte antigen 4 (CTLA-4) or the programmed cell death ligand 1/protein 1 pathway (PD-L1/PD-1)] or the stimulation of the patient's own immune system to produce a specific response. These strategies are obtaining better results in selected ADC patients.

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Section: Genome-guided Therapymentioning

confidence: 99%

Lung adenocarcinoma: from molecular basis to genome-guided therapy and immunotherapy

et al. 2017

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“…In addition to metastatic disease, osimertinib is being tested in the adjuvant setting (ADAURA study, NCT02511106). 23 …”

Section: Clinical Trialsmentioning

confidence: 99%

Treating <em>EGFR </em>mutation resistance in non-small cell lung cancer – role of osimertinib

Mazza¹,

Cappuzzo

2017

TACG

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The discovery of mutations in EGFR significantly changed the treatment paradigm of patients with EGFR-mutant non-small cell lung cancer (NSCLC), a particular group of patients with different clinical characteristics and outcome to EGFR-wild-type patients. In these patients, the treatment of choice as first-line therapy is first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, or afatinib. Inevitably, after the initial response, all patients become refractory to these drugs. The most common mechanism of acquired resistance to EGFR-TKIs is the development of a second mutation in exon 20 of EGFR (T790M). Osimertinib is a third-generation EGFR-TKI designed for overcoming T790M-mediated resistance. Based on the results of efficacy and tolerability of Phase II and Phase III studies, osimertinib has been approved for treatment of advanced EGFRT790M+ mutation NSCLC following progression on a prior EGFR-TKI. Occurrence of acquired resistance to osimertinib represents an urgent need for additional strategies including combination with other agents, such as other targeted therapies or checkpoint inhibitors, or development of new and more potent compounds.

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“…EGFR inhibitor can either be small-molecule tyrosine kinase inhibitors (TKIs) or monoclonal antibodies [30,31]. Tumors with EGFR expression and mutation are responsive to a particular TKIs, for example, gefitinib and erlotinib, first-generation EGFR TKIs, second-generation EGFR TKI, afatinib, and the third-generation EGFR TKI, osimertinib [32][33][34][35]. EGFRs are composed of four members, receptor tyrosine kinases that share akin structure and roles; ErbB1 (EGFR or HER1), ErbB2 (HER2), ErbB3 (HER3) andErbB4 (HER4).…”

Section: Epidermal Growth Receptors (Egfr)mentioning

confidence: 99%

Exploring receptor tyrosine kinases-inhibitors in Cancer treatments

Metibemu

Akinloye

Akamo

et al. 2019

Egypt J Med Hum Genet

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Background: Receptor tyrosine kinases (RTKs) are signaling enzymes responsible for the transfer of Adenosine triphosphate (ATP) γ-phosphate to the tyrosine residues substrates. RTKs demonstrate essential roles in cellular growth, metabolism, differentiation, and motility. Anomalous expression of RTK customarily leads to cell growth dysfunction, which is connected to tumor takeover, angiogenesis, and metastasis. Understanding the structure, mechanisms of adaptive and acquired resistance, optimizing inhibition of RTKs, and eradicating cum minimizing the havocs of quiescence cancer cells is paramount. MainText: Tyrosine kinase inhibitors (TKIs) vie with RTKs ATP-binding site for ATP and hitherto reduce tyrosine kinase phosphorylation, thus hampering the growth of cancer cells. TKIs can either be monoclonal antibodies that compete for the receptor's extracellular domain or small molecules that inhibit the tyrosine kinase domain and prevent conformational changes that activate RTKs. Progression of cancer is related to aberrant activation of RTKs due to due to mutation, excessive expression, or autocrine stimulation. Conclusions:Understanding the modes of inhibition and structures of RTKs is germane to the design of novel and potent TKIs. This review shed light on the structures of tyrosine kinases, receptor tyrosine kinases, tyrosine kinase inhibitors, minimizing imatinib associated toxicities, optimization of tyrosine kinase inhibition in curtailing quiescence in cancer cells and the prospects of receptor tyrosine kinase based treatments.

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Update on recent preclinical and clinical studies of T790M mutant-specific irreversible epidermal growth factor receptor tyrosine kinase inhibitors

Cited by 42 publications

References 79 publications

Lung adenocarcinoma: from molecular basis to genome-guided therapy and immunotherapy

Lung adenocarcinoma: from molecular basis to genome-guided therapy and immunotherapy

Treating <em>EGFR </em>mutation resistance in non-small cell lung cancer – role of osimertinib

Exploring receptor tyrosine kinases-inhibitors in Cancer treatments

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Update on recent preclinical and clinical studies of T790M mutant-specific irreversible epidermal growth factor receptor tyrosine kinase inhibitors

Cited by 42 publications

References 79 publications

Lung adenocarcinoma: from molecular basis to genome-guided therapy and immunotherapy

Lung adenocarcinoma: from molecular basis to genome-guided therapy and immunotherapy

Treating <em>EGFR </em>mutation resistance in non-small cell lung cancer &ndash;&nbsp;role of osimertinib

Exploring receptor tyrosine kinases-inhibitors in Cancer treatments

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Product

Resources

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Treating <em>EGFR </em>mutation resistance in non-small cell lung cancer – role of osimertinib