Parallel phase 1 clinical trials in the US and in China: accelerating the test of avitinib in lung cancer as a novel inhibitor selectively targeting mutated EGFR and overcoming T790M-induced resistance
نویسنده
چکیده
Avitinib, a new generation inhibitor of epidermal growth factor receptor (EGFR), was approved for clinical trial in both China and the United States, and the phase 1 trials were initiated in both countries in parallel. In the preclinical studies, avitinib showed three novel features including (1) irreversibly binding EGFR by forming a covalent bound with Cys 797 in the ATP-binding pocket, (2) sparing wild-type EGFR, and (3) overcoming T790M-induced resistance. Avitinib is the first China-developed novel EGFR inhibitor that has entered in global clinical trials, and will provide a precision targeted therapy for non-small cell lung cancer patients.
منابع مشابه
Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer.
The tyrosine kinase inhibitors (TKI) against epidermal growth factor receptor (EGFR) are widely used in patients with non-small cell lung cancer (NSCLC). However, EGFR T790M mutation leads to resistance to most clinically available EGFR TKIs. Third-generation EGFR TKIs against the T790M mutation have been in active clinical development. These agents include osimertinib, rociletinib, HM61713, AS...
متن کاملEGFR C797S mutation mediates resistance to third-generation inhibitors in T790M-positive non-small cell lung cancer
T790M mutation is the most common mechanism for resistance to first- and second-generation tyrosine kinase inhibitors (TKI) for epidermal growth factor receptor (EGFR). Several third-generation EGFR mutant selective TKIs are being explored to conquer this resistance. AZD9291 (osimertinib, tagrisso) has been approved for treatment of the metastatic EGFR T790M mutation-positive non-small cell lun...
متن کاملOsimertinib in the treatment of non-small-cell lung cancer: design, development and place in therapy
The discovery of epidermal growth factor receptor (EGFR) mutations and subsequent demonstration of the efficacy of genotype-directed therapies with EGFR tyrosine kinase inhibitors (TKIs) marked the advent of the era of precision medicine for non-small-cell lung cancer (NSCLC). First- and second-generation EGFR TKIs, including erlotinib, gefitinib and afatinib, have consistently shown superior e...
متن کاملEpidermal growth factor receptor T790M mutation-positive metastatic non-small-cell lung cancer: focus on osimertinib (AZD9291)
Adenocarcinoma is the most common type of non-small-cell lung cancer (NSCLC). Adenocarcinoma with epidermal growth factor receptor (EGFR) mutations accounts for 8%-30% of all cases of NSCLC depending on the geography and ethnicity. EGFR-mutated NSCLC usually responds to first-line therapy with EGFR tyrosine kinase inhibitors (TKIs). However, there is eventual loss of efficacy to TKIs due to dev...
متن کاملATM induces radioresistance of non-small cell lung cancer A549 cells by downregulation of MDMX
Background: Tumor radioresistance leads to a reduction in the efficiency of radiation therapy. It is very important to explore the cellular mechanisms leading to radioresistance and to find potential therapeutic targets, which might improve the efficacy of radiation therapy. This study was to investigate the role of ataxia-telangiectasia mutated (ATM) and murine double minute X (MDMX) in radior...
متن کامل