ترجمه مقاله نقش ضروری ارتباطات 6G با چشم انداز صنعت 4.0
- مبلغ: ۸۶,۰۰۰ تومان
ترجمه مقاله پایداری توسعه شهری، تعدیل ساختار صنعتی و کارایی کاربری زمین
- مبلغ: ۹۱,۰۰۰ تومان
Despite advances in cancer biology and therapeutics, drug resistance remains problematic. Resistance is often multifactorial, heterogeneous, and prone to undersampling. Nonetheless, many individual mechanisms of targeted therapy resistance may coalesce into a smaller number of convergences, including pathway reactivation (downstream re-engagement of original effectors), pathway bypass (recruitment of a parallel pathway converging on the same downstream output), and pathway indifference (development of a cellular state independent of the initial therapeutic target). Similar convergences may also underpin immunotherapy resistance. Such parsimonious, convergence-based frameworks may help explain resistance across tumor types and therapeutic categories and may also suggest strategies to overcome it.
Conclusion
Although the multifactorial and heterogeneous nature of cancer drug resistance remains a significant challenge, systematic experimental and clinical studies across many cancer types have revealed a wealth of resistance mechanisms. This review has proposed a convergence-based framework—pathway reactivation, pathway bypass, and pathway indifference—to organize the multiplicity of individual resistance mechanisms to targeted therapeutics into a parsimonious set of generalizable principles. Importantly, this framework may not prove comprehensive, nor is it intended to be proscriptive. Rather, it seems likely that additional as-yet unsuspected convergences will emerge. Nonetheless, the most fundamental lesson from such consideration may not be the identity of specific resistance convergences themselves, but rather that even highly complex landscapes of resistance can be understood through the paradigm of convergence. Going forward, such frameworks may provide both explanatory power to aid biological understanding and predictive power to guide future therapeutic approaches. Ultimately, these insights may help to achieve durable disease control in patients with advanced cancer.