Spies, Nicholas C.
https://orcid.org/0000-0002-5873-351X
Mayo Clinic
Washington University in St. Louis
Citations 2
CIViCdb 2022: evolution of an open-access cancer variant interpretation knowledgebase
Krysiak, Kilannin , Danos, Arpad , McMichael, Joshua F. , Coffman, Adam , Kiwala, Susanna , Sheta, Lana , Kujan, Lynzey , Pema, Shahil , Ridd, Sarah , Spies, Nicholas C. , Andric, Veronica , Chiorean, Andreea , Rieke, Damian , Clark, Kaitlin A., Reisle, Caralyn , Venigalla, Ajay C, Jani, Payal , Takahashi, Hideaki , Suda, Avila, Horak, Peter , Ritter, Deborah , DeLong, Sean , Lamping, Mario , Shen, Haolin , Marr, Alexander , Hoang, My , Singhal, Kartik , Khanfar, Mariam , Li, Brian V , Lin, Wan‐Hsin , Terraf, Panieh, Corson, Laura , Salama, Yasser, Farncombe, Kirsten M. , Ji, Jianling , Zhao, Xiaonan, Xu, Xinjie , Kanagal‐Shamanna, Rashmi , Walker, Jason , Zhang, Jinghui , Patel, Ronak Y. , Kim, Raymond H. , Jones, Steven J.M. , Raca, Gordana , Madhavan, Subha , Griffith, Malachi , Griffith, Obi L. , Coffman, Adam C , Kiwala, Susanna , Zhou, Xin , Campbell, Katie M , Ji, Jianling , Cotto, Kelsy C , Schriml, Lynn M , Wagner, Alex H , Griffith, Malachi , Griffith, Obi L , Krysiak, Kilannin , Kanagal-Shamanna, Rashmi , Kim, Raymond H , Saliba, Jason , Barnell, Erica K. , Grisdale, Cameron J. , Lever, Jake , Venigalla, Ajay , Evans, Mark G. , Ainscough, Benjamin J. , Kesserwan, Chimene A. , Zhao, Xiaonan, King, Ian F. G. , Skidmore, Zachary L. , Milosavljevic, Aleksandar , Giles, Rachel H. , Mardis, Elaine R. , Rao, Shruti , Wagner, Alex H. , Khanfar, Mariam
Nucleic Acids Research | October 15, 2022 | Volume: 51 | Issue: D1 | Pages: D1230-D1241
Abstract CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is a crowd-sourced, public domain knowledgebase composed of literature-derived evidence characterizing the clinical utility of cancer variants. As clinical sequencing becomes more prevalent in cancer management, the need for cancer variant interpretation has grown beyond the capability of any single institution. CIViC contains peer-reviewed, published literature curated and expertly-moderated into structured data units (Evidence Items) that can be accessed globally and in real time, reducing barriers to clinical variant knowledge sharing. We have extended CIViC’s functionality to support emergent variant interpretation guidelines, increase interoperability with other variant resources, and promote widespread dissemination of structured curated data. To support the full breadth of variant interpretation from basic to translational, including integration of somatic and germline variant knowledge and inference of drug response, we have enabled curation of three new Evidence Types (Predisposing, Oncogenic and Functional). The growing CIViC knowledgebase has over 300 contributors and distributes clinically-relevant cancer variant data currently representing >3200 variants in >470 genes from >3100 publications.
NeoPalAna: Neoadjuvant Palbociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor, and Anastrozole for Clinical Stage 2 or 3 Estrogen Receptor–Positive Breast Cancer
Cynthia, X. , Northfelt, Donald W. , Forero, Andres , Anderson, Karen S. , Margenthaler, Julie A. , Aft, Rebecca , Hobday, Timothy J. , Moynihan, Timothy J. , Gillanders, William E. , Cyr, Amy, Eberlein, Timothy J. , Guo, Zhanfang , Lee, Michelle V. , Spies, Nicholas C. , Skidmore, Zachary L. , Griffith, Obi L. , Griffith, Malachi , Thomas, Shana , Bumb, Caroline, Bartlett, Cynthia Huang , Koehler, María , Al‐Kateb, Hussam , Sanati, Souzan , Hobday, Timothy, Moynihan, Timothy, Hieken, Tina, Gao, Feng , Luo, Jingqin , Goetz, Matthew P. , Hoog, Jeremy , Naughton, Michael J. , Ademuyiwa, Foluso O. , Suresh, Rama , Hieken, Tina J. , Krontiras, Helen , Vij, Kiran R , Ellis, Matthew J. , Griffith, Malachi , Griffith, Obi L
Clinical Cancer Research | March 7, 2017 | Volume: 23 | Issue: 15 | Pages: 4055-4065
Abstract Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor–positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the antiproliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies. Experimental Design: Eligible patients with clinical stage II/III ER+/HER2− breast cancer received anastrozole 1 mg daily for 4 weeks (cycle 0; with goserelin if premenopausal), followed by adding palbociclib (125 mg daily on days 1–21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67 > 10%, in which case patients went off study due to inadequate response. Anastrozole was continued until surgery, which occurred 3 to 5 weeks after palbociclib exposure. Later patients received additional 10 to 12 days of palbociclib (Cycle 5) immediately before surgery. Serial biopsies at baseline, C1D1, C1D15, and surgery were analyzed for Ki67, gene expression, and mutation profiles. The primary endpoint was complete cell cycle arrest (CCCA: central Ki67 ≤ 2.7%). Results: Fifty patients enrolled. The CCCA rate was significantly higher after adding palbociclib to anastrozole (C1D15 87% vs. C1D1 26%, P < 0.001). Palbociclib enhanced cell-cycle control over anastrozole monotherapy regardless of luminal subtype (A vs. B) and PIK3CA status with activity observed across a broad range of clinicopathologic and mutation profiles. Ki67 recovery at surgery following palbociclib washout was suppressed by cycle 5 palbociclib. Resistance was associated with nonluminal subtypes and persistent E2F-target gene expression. Conclusions: Palbociclib is an active antiproliferative agent for early-stage breast cancer resistant to anastrozole; however, prolonged administration may be necessary to maintain its effect. Clin Cancer Res; 23(15); 4055–65. ©2017 AACR.