The care of T790M change-positive NSCLC (NSCLC) has been transformed by the drug, a latest TKI (TKI).However, tolerance to the drug remains a significant challenge in medical use.This article aims to provide a detailed summary of the various tolerance mechanisms associated with the drug in T790M change-positive NSCLC, with a focus on recent advancements and potential strategies for overcoming tolerance.
The first mechanism is the epidermal growth factor receptor T790M change and the drug tolerance:In T790M change-positive NSCLC, the epidermal growth factor receptor T790M change is the most common tolerance mechanism to the drug.This change confers tolerance by creating a shape alteration in the ADP-binding site of the epidermal growth factor receptor enzyme region, thereby rendering the drug non-effective.
Comprehending the molecular foundation of this resistance process is essential for creating successful tactics to defeat it.The subsequent mechanism involves secondary resistance mutations:Following the initial reaction to osimertinib treatment, secondary resistance mutations may emerge, resulting in additional resistance.This section examines the different secondary resistance mutations, such as MET amplification, HER2 alteration, and other epidermal growth factor receptor mutations, and their consequences for therapeutic approaches.
The third aspect involves non-molecular resistance mechanisms:Apart from molecular resistance mechanisms, non-molecular elements such as tumor heterogeneity, immune avoidance, and stromal interactions can contribute to osimertinib treatment resistance.This section investigates the role of these non-molecular elements in the development of resistance and their potential as treatment targets.
The fourth strategy is combined treatments and tailored medicine:combined treatments and tailored medicine approaches are emerging as hopeful approaches for beating osimertinib resistance in EGFR T790M-positive non-small cell lung cancer.This section discusses the potential of combining osimertinib with other specific drugs, immunological treatments, and chemotherapeutic agents, as well as the importance of identifying and treating patients with specific genetic backgrounds.
Osimertinib resistance in EGFR T790M-positive non-small cell lung cancer is a complicated and multi-causal problem.Understanding the various resistance pathways, including the EGFR T790M alteration, subsequent resistance mutations, non-molecular influences, and the potential for combined treatments and tailored medicine, is crucial for creating successful treatment plans.
By addressing these challenges, we can enhance results for patients with EGFR T790M-positive non-small cell lung cancer and overcome the limitations of osimertinib resistance.
