التفاصيل البيبلوغرافية
| العنوان: |
Resistance to receptor-blocking therapies primes tumors as targets for HER3-homing nanobiologics |
| المؤلفون: |
Sims, Jessica D., Taguiam, Jan Michael, Alonso-Valenteen, Felix, Markman, Janet, Agadjanian, Hasmik, Chu, David, Lubow, Jay, Abrol, Ravinder, Srinivas, Dustin, Jain, Anjali, Han, Bingchen, Qu, Ying, Mirzadehgan, Parisa, Hwang, Jae-Youn, Rentsendorj, Altan, Chung, Alice, Lester, Jenny, Karlan, Beth Y., Gray, Harry B., Gross, Zeev, Giuliano, Armando, Cui, Xiaojiang, Medina-Kauwe, Lali K. |
| المصدر: |
Journal of Controlled Release, 271, 127-138, (2018-02-10) |
| بيانات النشر: |
Elsevier |
| سنة النشر: |
2018 |
| المجموعة: |
Caltech Authors (California Institute of Technology) |
| مصطلحات موضوعية: |
HER3, Neuregulin, Target, Tumor, Therapeutic, Nanobiologic, Resistance |
| الوصف: |
Resistance to anti-tumor therapeutics is an important clinical problem. Tumor-targeted therapies currently used in the clinic are derived from antibodies or small molecules that mitigate growth factor activity. These have improved therapeutic efficacy and safety compared to traditional treatment modalities but resistance arises in the majority of clinical cases. Targeting such resistance could improve tumor abatement and patient survival. A growing number of such tumors are characterized by prominent expression of the human epidermal growth factor receptor 3 (HER3) on the cell surface. This study presents a "Trojan-Horse" approach to combating these tumors by using a receptor-targeted biocarrier that exploits the HER3 cell surface protein as a portal to sneak therapeutics into tumor cells by mimicking an essential ligand. The biocarrier used here combines several functions within a single fusion protein for mediating targeted cell penetration and non-covalent self-assembly with therapeutic cargo, forming HER3-homing nanobiologics. Importantly, we demonstrate here that these nanobiologics are therapeutically effective in several scenarios of resistance to clinically approved targeted inhibitors of the human EGF receptor family. We also show that such inhibitors heighten efficacy of our nanobiologics on naïve tumors by augmenting HER3 expression. This approach takes advantage of a current clinical problem (i.e. resistance to growth factor inhibition) and uses it to make tumors more susceptible to HER3 nanobiologic treatment. Moreover, we demonstrate a novel approach in addressing drug resistance by taking inhibitors against which resistance arises and re-introducing these as adjuvants, sensitizing tumors to the HER3 nanobiologics described here. ; © 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0Test/). Received 12 August 2017; revised 9 December 2017; accepted 21 December 2017; available online 27 December ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| العلاقة: |
https://doi.org/10.1016/j.jconrel.2017.12.024Test; oai:authors.library.caltech.edu:m4amq-66h93; eprintid:84163; resolverid:CaltechAUTHORS:20180108-103844165 |
| DOI: |
10.1016/j.jconrel.2017.12.024 |
| الإتاحة: |
https://doi.org/10.1016/j.jconrel.2017.12.024Test |
| حقوق: |
info:eu-repo/semantics/openAccess ; Other |
| رقم الانضمام: |
edsbas.CE0FDE76 |
| قاعدة البيانات: |
BASE |
