Recent Advances in Boosting EGFR Tyrosine Kinase Inhibitors-Based Cancer Therapy

Abstract

Epidermal growth factor receptor (EGFR) plays a key role in signal transduction pathways associated with cell proliferation, growth, and survival. Its overexpression and aberrant activation in malignancy correlate with poor prognosis and short survival. Targeting inhibition of EGFR by small-molecular tyrosine kinase inhibitors (TKIs) is emerging as an important treatment model besides of chemotherapy, greatly reshaping the landscape of cancer therapy. However, they are still challenged by the offtargeted toxicity, relatively limited cancer types, and drug resistance after long-term therapy. In this review, we summarize the recent progress of oral, pulmonary, and injectable drug delivery systems for enhanced and targeting TKI delivery to tumors and reduced side effects. Importantly, EGFR-TKI-based combination therapies not only greatly broaden the applicable cancer types of EGFR-TKI but also significantly improve the anticancer effect. The mechanisms of TKI resistance are summarized, and current strategies to overcome TKI resistance as well as the application of TKI in reversing chemotherapy resistance are discussed. Finally, we provide a perspective on the future research of EGFR-TKI-based cancer therapy.

SUMOylation of AnxA6 facilitates EGFR-PKCα complex formation to suppress epithelial cancer growth

“…So far, the EGFR inhibition has been established a major therapeutic target in cancer therapy, particularly for tumors of breast, cervix, ovaries, kidney, esophagus, prostate and NSCLC [15][16][17][18]. EGFR-TKIs, such as gefitinib, erlotinib, afatinib, dacomitinib and osimertinib, have improved the outcomes of EGFR-dependent cancers for many patients [52].…”

“…This high incidence of EGFR-related cancers and its association with poor clinical outcomes pave way for development of therapeutic interventions, including small-molecule tyrosine kinase inhibitors (TKIs), including the first-generation gefitinib, erlotinib and icotinib, the second-generation afatinib and dacomitinib and the third-generation osimertinib [ 14 , 15 ]. The first generation TKIs are typically used to treat patients with high EGFR expression who carry L858R or exon 19 deletion mutations but were resisted by a second mutation T790M.…”

Electrosprayed Eudragit RL100 nanoparticles with Janus polyvinylpyrrolidone patches for multiphase release of paracetamol

“…The blood drug concentration is viewed as a key parameter to evaluate their therapeutic effects. [77][78][79] The pharmacokinetic profiles of the plasma drug concentration vs. time after oral administration through gavage are depicted in Fig. 9.…”

Tumor‐targeted and microenvironment‐activatable iron‐based nMOF for synergistic inducing ferroptosis

“…[14][15][16] Nanomedicine carriers are used as delivery tools to deliver drugs to the affected area, change the in vivo distribution, reduce the retention of drugs in the nonaffected area, and enrich drugs in tumor tissues to achieve the purpose of reducing toxicity and side effects and increasing bioavailability. 17,18 The level of intracellular iron content is crucial for the induction of ferroptosis. Iron ions can react with peroxide (H 2 O 2 ) to generate toxic hydroxyl radical (•OH) through the Fenton reaction and then react with intracellular polyunsaturated fatty acids to generate lipid peroxides (LPOs), inducing ferroptosis.…”