التفاصيل البيبلوغرافية
| العنوان: |
Data from ONC201 Targets AR and AR-V7 Signaling, Reduces PSA, and Synergizes with Everolimus in Prostate Cancer |
| المؤلفون: |
Wafik S. El-Deiry, David T. Dicker, Petr B. Makhov, Marie D. Ralff, Brian C. Ross, Amriti R. Lulla, Avital Lev |
| بيانات النشر: |
American Association for Cancer Research (AACR), 2023. |
| سنة النشر: |
2023 |
| الوصف: |
Androgen receptor (AR) signaling plays a key role in prostate cancer progression, and androgen deprivation therapy (ADT) is a mainstay clinical treatment regimen for patients with advanced disease. Unfortunately, most prostate cancers eventually become androgen-independent and resistant to ADT with patients progressing to metastatic castration-resistant prostate cancer (mCRPC). Constitutively activated AR variants (AR-V) have emerged as mediators of resistance to AR-targeted therapy and the progression of mCRPC, and they represent an important therapeutic target. Out of at least 15 AR-Vs described thus far, AR-V7 is the most abundant, and its expression correlates with ADT resistance. ONC201/TIC10 is the founding member of the imipridone class of small molecules and has shown anticancer activity in a broad range of tumor types. ONC201 is currently being tested in phase I/II clinical trials for advanced solid tumors, including mCRPC, and hematologic malignancies. There has been promising activity observed in patients in early clinical testing. This study demonstrates preclinical single-agent efficacy of ONC201 using in vitro and in vivo models of prostate cancer. ONC201 has potent antiproliferative and proapoptotic effects in both castration-resistant and -sensitive prostate cancer cells. Furthermore, the data demonstrate that ONC201 downregulates the expression of key drivers of prostate cancer such as AR-V7 and downstream target genes including the clinically used biomarker PSA (KLK3). Finally, the data also provide a preclinical rationale for combination of ONC201 with approved therapeutics for prostate cancer such as enzalutamide, everolimus (mTOR inhibitor), or docetaxel.Implications: The preclinical efficacy of ONC201 as a single agent or in combination, in hormone-sensitive or castration-resistant prostate cancer, suggests the potential for immediate clinical translation. Mol Cancer Res; 16(5); 754–66. ©2018 AACR. |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1ee219a9fe8b608832c44ed06ad66c01
https://doi.org/10.1158/1541-7786.c.6540340.v1 |
| حقوق: |
OPEN |
| رقم الأكسشن: |
edsair.doi.dedup.....1ee219a9fe8b608832c44ed06ad66c01 |
| قاعدة البيانات: |
OpenAIRE |
