دانلود رایگان مقاله انگلیسی یک چارچوب مبتنی بر همگرایی برای مقاومت دارویی در برابر سرطان - الزویر 2018

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عنوان فارسی

یک چارچوب مبتنی بر همگرایی برای مقاومت دارویی در برابر سرطان

عنوان انگلیسی

A Convergence-Based Framework for Cancer Drug Resistance

صفحات مقاله فارسی

0

صفحات مقاله انگلیسی

15

سال انتشار

2018

نشریه

الزویر - Elsevier

فرمت مقاله انگلیسی

PDF

نوع مقاله

ISI

نوع نگارش

مقالات مروری

رفرنس

دارد

پایگاه

اسکوپوس

کد محصول

E9505

رشته های مرتبط با این مقاله

داروسازی

گرایش های مرتبط با این مقاله

داروشناسی

مجله

سلول سرطانی - Cancer Cell

دانشگاه

Harvard Radiation Oncology Program - Boston - MA - USA

doi یا شناسه دیجیتال

https://doi.org/10.1016/j.ccell.2018.03.025

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چکیده

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.

نتیجه گیری

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.

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