Shailender S Chauhan, Rachel K Toth, Corbin C Jensen, Andrea L Casillas, David F Kashatus, Noel A Warfel,
Resistance to chemotherapy represents a major obstacle to the successful treatment of non-small-cell lung cancer (NSCLC). The goal of this study was to determine how PIM kinases impact mitochondrial dynamics, ROS production, and response to chemotherapy in lung cancer. Live-cell imaging and microscopy were used to determine the effect of ... Read more >>
Oncogene (Oncogene)
[2020, 39(12):2597-2611]
Cited: 1 time
Rachel K Toth, Jack D Tran, Michelle T Muldong, Eric A Nollet, Veronique V Schulz, Corbin C Jensen, Lori A Hazlehurst, Eva Corey, Donald Durden, Christina Jamieson, Cindy K Miranti, Noel A Warfel,
Bone-metastatic castration-resistant prostate cancer (CRPC) is lethal due to inherent resistance to androgen deprivation therapy, chemotherapy, and targeted therapies. Despite the fact that a majority of CRPC patients (approximately 70%) harbor a constitutively active PI3K survival pathway, targeting the PI3K/mTOR pathway has failed to increase overall survival in clinical trials. ... Read more >>
Am J Clin Exp Urol (American journal of clinical and experimental urology)
[2019, 7(4):297-312]
Cited: 0 times
Cynthia S Rubenstein, Jaime M C Gard, Mengdie Wang, Julie E McGrath, Nadia Ingabire, James P Hinton, Kendra D Marr, Skyler J Simpson, Raymond B Nagle, Cindy K Miranti, Noel A Warfel, Joe G N Garcia, Hina Arif-Tiwari, Anne E Cress,
Human prostate cancer confined to the gland is indolent (low-risk), but tumors outside the capsule are aggressive (high-risk). Extracapsular extension requires invasion within and through a smooth muscle-structured environment. Because integrins respond to biomechanical cues, we used a gene editing approach to determine if a specific region of laminin-binding α6β1 ... Read more >>
Cancer Res. (Cancer research)
[2019, 79(18):4703-4714]
Cited: 0 times
William L Harryman, Noel A Warfel, Raymond B Nagle, Anne E Cress,
Localized prostate cancer (confined to the gland) generally is considered curable, with nearly a 100% 5-year-survival rate. When the tumor escapes the prostate capsule, leading to metastasis, there is a poorer prognosis and higher mortality rate, with 5-year survival dropping to less than 30%. A major research question has been ... Read more >>
Adv. Exp. Med. Biol. (Advances in experimental medicine and biology)
[2019, 1210:149-170]
Cited: 0 times
Jin H Song, Neha Singh, Libia A Luevano, Sathish K R Padi, Koichi Okumura, Virginie Olive, Stephen M Black, Noel A Warfel, David W Goodrich, Andrew S Kraft,
Cancer resistance to PI3K inhibitor therapy can be in part mediated by increases in the PIM1 kinase. However, the exact mechanism by which PIM kinase promotes tumor cell resistance is unknown. Our study unveils the pivotal control of redox signaling by PIM kinases as a driver of this resistance mechanism. ... Read more >>
Mol. Cancer Ther. (Molecular cancer therapeutics)
[2018, 17(12):2710-2721]
Cited: 6 times
Shailender S Chauhan, Noel A Warfel,
Oncoscience (Oncoscience)
[2018, 5(9-10):254-255]
Cited: 0 times
Andrea L Casillas, Rachel K Toth, Alva G Sainz, Neha Singh, Ankit A Desai, Andrew S Kraft, Noel A Warfel,
Purpose: Patients develop resistance to antiangiogenic drugs, secondary to changes in the tumor microenvironment, including hypoxia. PIM kinases are prosurvival kinases and their expression increases in hypoxia. The goal of this study was to determine whether targeting hypoxia-induced PIM kinase expression is effective in combination with VEGF-targeting agents. The rationale ... Read more >>
Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2018, 24(1):169-180]
Cited: 8 times
Cell Cycle (Cell cycle (Georgetown, Tex.))
[2017, 16(13):1241-1242]
Cited: 0 times
The importance of the tumor microenvironment for cancer progression and therapeutic resistance is an emerging focus of cancer biology. Hypoxia, or low oxygen, is a hallmark of solid tumors that promotes metastasis and represents a significant obstacle to successful cancer therapy. In response to hypoxia, cancer cells activate a transcriptional ... Read more >>
Antioxidants (Basel) (Antioxidants (Basel, Switzerland))
[2017, 6(2):]
Cited: 12 times
Noel A Warfel, Alva G Sainz, Jin H Song, Andrew S Kraft,
Intratumoral hypoxia is a significant obstacle to the successful treatment of solid tumors, and it is highly correlated with metastasis, therapeutic resistance, and disease recurrence in cancer patients. As a result, there is an urgent need to develop effective therapies that target hypoxic cells within the tumor microenvironment. The Proviral ... Read more >>
Mol. Cancer Ther. (Molecular cancer therapeutics)
[2016, 15(7):1637-1647]
Cited: 9 times
Jin H Song, Sathish K R Padi, Libia A Luevano, Mark D Minden, Daniel J DeAngelo, Gary Hardiman, Lauren E Ball, Noel A Warfel, Andrew S Kraft,
The Pim family of serine/threonine protein kinases (Pim 1, 2, and 3) contribute to cellular transformation by regulating glucose metabolism, protein synthesis, and mitochondrial oxidative phosphorylation. Drugs targeting the Pim protein kinases are being tested in phase I/II clinical trials for the treatment of hematopoietic malignancies. The goal of these ... Read more >>
Oncotarget (Oncotarget)
[2016, 7(15):20152-20165]
Cited: 9 times
Shengliang Zhang, Lanlan Zhou, Bo Hong, A Pieter J van den Heuvel, Varun V Prabhu, Noel A Warfel, Christina Leah B Kline, David T Dicker, Levy Kopelovich, Wafik S El-Deiry,
The tumor-suppressor p53 prevents cancer development via initiating cell-cycle arrest, cell death, repair, or antiangiogenesis processes. Over 50% of human cancers harbor cancer-causing mutant p53. p53 mutations not only abrogate its tumor-suppressor function, but also endow mutant p53 with a gain of function (GOF), creating a proto-oncogene that contributes to ... Read more >>
Cancer Res. (Cancer research)
[2015, 75(18):3842-3852]
Cited: 39 times
Noel A Warfel, Andrew S Kraft,
The initiation and progression of human cancer is frequently linked to the uncontrolled activation of survival kinases. Two such pro-survival kinases that are commonly amplified in cancer are PIM and Akt. These oncogenic proteins are serine/threonine kinases that regulate tumorigenesis by phosphorylating substrates that control the cell cycle, cellular metabolism, ... Read more >>
Pharmacol. Ther. (Pharmacology & therapeutics)
[2015, 151:41-49]
Cited: 53 times
Noel A Warfel, Nathan G Dolloff, David T Dicker, Jozef Malysz, Wafik S El-Deiry,
Hypoxia-inducible factor 1 (HIF-1) is a major mediator of tumor physiology, and its activation is correlated with tumor progression, metastasis, and therapeutic resistance. HIF-1 is activated in a broad range of solid tumors due to intratumoral hypoxia or genetic alterations that enhance its expression or inhibit its degradation. As a ... Read more >>
Cell Cycle (Cell cycle (Georgetown, Tex.))
[2013, 12(23):3689-3701]
Cited: 38 times
Noel A Warfel, Wafik S El-Deiry,
PURPOSE OF REVIEW: This review provides an overview of the structure, regulation and physiological functions of p21, the product of the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene, with a focus on its dual role in promoting and repressing biological processes that are hallmarks of tumourigenesis. RECENT FINDINGS: Recent work has ... Read more >>
Curr Opin Oncol (Current opinion in oncology)
[2013, 25(1):52-58]
Cited: 150 times
Varun V Prabhu, Noel A Warfel, Wafik S El-Deiry,
Cell Cycle (Cell cycle (Georgetown, Tex.))
[2012, 11(14):2592-2593]
Cited: 4 times
Noel A Warfel, Matt Niederst, Alexandra C Newton,
The pro-survival kinase Akt requires phosphorylation at two conserved residues, the activation loop site (Thr-308) and the hydrophobic motif site (Ser-473), for maximal activation. Previous reports indicate that mTORC2 is necessary for phosphorylation of the hydrophobic motif and that this site is not phosphorylated in cells lacking components of the ... Read more >>
J. Biol. Chem. (The Journal of biological chemistry)
[2011, 286(45):39122-39129]
Cited: 22 times
Noel A Warfel, Alexandra C Newton,
Precise balance between phosphorylation, catalyzed by protein kinases, and dephosphorylation, catalyzed by protein phosphatases, is essential for cellular homeostasis. Deregulation of this balance leads to pathophysiological states that drive diseases such as cancer, heart disease, and diabetes. The recent discovery of the PHLPP (pleckstrin homology domain leucine-rich repeat protein phosphatase) ... Read more >>
J. Biol. Chem. (The Journal of biological chemistry)
[2012, 287(6):3610-3616]
Cited: 39 times
Noel A Warfel, Matt Niederst, Michael W Stevens, Paul M Brennan, Margaret C Frame, Alexandra C Newton,
The PH domain leucine-rich repeat protein phosphatase, PHLPP, plays a central role in controlling the amplitude of growth factor signaling by directly dephosphorylating and thereby inactivating Akt. The cellular levels of PHLPP1 have recently been shown to be enhanced by its substrate, activated Akt, via modulation of a phosphodegron recognized ... Read more >>
J. Biol. Chem. (The Journal of biological chemistry)
[2011, 286(22):19777-19788]
Cited: 22 times
Joell J Gills, Jaclyn Lopiccolo, Junji Tsurutani, Robert H Shoemaker, Carolyn J M Best, Mones S Abu-Asab, Jennifer Borojerdi, Noel A Warfel, Erin R Gardner, Matthew Danish, M Christine Hollander, Shigeru Kawabata, Maria Tsokos, William D Figg, Patricia S Steeg, Phillip A Dennis,
PURPOSE:The development of new cancer drugs is slow and costly. HIV protease inhibitors are Food and Drug Administration approved for HIV patients. Because these drugs cause toxicities that can be associated with inhibition of Akt, an emerging target in cancer, we assessed the potential of HIV protease inhibitors as anticancer ... Read more >>
Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2007, 13(17):5183-5194]
Cited: 161 times
Noel A Warfel, Erin R Lepper, Chunyu Zhang, William D Figg, Phillip A Dennis,
Thalidomide has gained renewed interest as a cancer therapeutic due to its potential antiangiogenic effects. The thalidomide analogues CPS11 and CPS49 are active in preclinical angiogenesis assays and xenograft model systems, but the biochemical basis for these observations is unclear.To address this question, we assessed the toxicity of these thalidomide ... Read more >>
Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2006, 12(11 Pt 1):3502-3509]
Cited: 12 times