Everolimus/Afinitor’s generational division of targeted drugs

In the history of targeted therapy development,the concept of "generation" is more used to describe the evolution of drug development logic and mechanism of action, rather than simply sorting by time on the market. Everolimus(Everolimus), as an mTOR inhibitor, its generational division is often different from the linear update model of EGFR or HER2-targeted drugs. The mTOR pathway is located downstream of the PI3K-AKT signaling axis and is an important hub for cell growth, metabolism and drug resistance formation. Therefore, everolimus is considered a precision intervention drug with a "pathway level further downstream".

From the perspective of target strategy, everolimus does not target a single receptor mutation, but indirectly affects the response of tumor cells to growth signals and nutritional signals by inhibiting themTORC1 complex. This makes it closer to a "mechanistic targeted drug" in the targeted drug spectrum, rather than a "first- and second-generation" receptor inhibitor in the traditional sense. In overseas literature, it is more commonly classified as "endocrine resistance reversal targeted drug" or "representative of pathway inhibition targeted therapy".

If understood from the perspective of the evolution of breast cancer treatment strategies, everolimus can be regarded as an important supplementary stage after simple endocrine therapy to delay or overcome the emergence of drug resistance. This positioning determines that it will not be simply replaced by higher-generation drugs, but will continue to retain clinical value at specific treatment points. For this reason, international guidelines still retain the recommended position of everolimus in multiple updates, reflecting its "platform" role in the targeted therapy system.

Therefore, rather than simply discussing which generation of targeted drugs everolimus belongs to, it is better to understand it as an important sign that targeted therapy has moved from the "receptor level" to the "signaling pathway level", and its intergenerational significance is more reflected in the upgrade of treatment concepts.

Reference materials:https://www.drugs.com/everolimus.html