tbuckley/cabot-search huggingface dataset:
Phase I trial of pulse-dose vorinostat with flavopiridol in solid tumors.
Authors: M. A. Dickson, D. E. Rathkopf, S. Grant, J. D. Roberts, J. M. Reid, M. M. Ames, R. M. McGovern, M. Gonen, H. J. Dials, G. K. Schwartz
Journal: Journal of Clinical Oncology (2010)

e13511 Background: Preclinical data show that the histone deacetylase inhibitor vorinostat (V) enhances chemotherapy at levels of > 2.5 μM. However the approved oral dose of V of 400 mg/d inconsistently achieves this level in pts. We sought to develop an intermittent oral pulse-dose schedule of V to increase serum drug levels. We combined V with the pan-cyclin dependent kinase inhibitor flavopiridol (F) based on data that sequential treatment with F increases V-induced apoptosis. Methods: This is a phase I trial of V + F in pts with advanced solid tumors. One week before combination therapy, V alone was given daily PO for 3 d (cycle -1). Combination treatment began with cycle 1. V was initially given on d 1-3 and 8-10 of each 21-d cycle. F was given IV on d 2 and d 9 of each cycle. Due to neutropenia, this was modified to V on d 1-3 and 15-17, and F on d 2 and 16, of each 28-d cycle. A split-dose schedule of F 30 mg/m2 over 30 min followed by 30 mg/m2 over 4 h was also investigated. Results: 34 pts were treated; 31 were evaluable for response. Pt characteristics: median age 59 (range 38-85), ECOG PS 1 (0- 1), prior regimens 4 (1-11). With V given on d 1-3 and 8-10, the maximum tolerated dose (MTD) was V 600 mg/d and F 60 mg/m2 over 1 h. Dose-limiting toxicities (DLT) were neutropenia, leukopenia, thrombocytopenia, hemorrhage, and pulmonary embolus. With V given on d 1-3 and 15-17, the MTD was V 800 mg/d and F 30 mg/m2over 30 min and 30 mg/m2 over 4 h. DLTs were neutropenia and infection. V pharmacokinetics increased with dose and the increase was greater than proportional. Mean V Cmax of pts treated at the 800 mg dose was 4.8 μM (± 2.8). V Cmax ≥ 2.5 μM was achieved in 86% of pts treated at the MTD. F co-administration increased the Cmax of V by 27% (95% CI 11%-43%). Flavopiridol Cmax of ≥ 2 μM was achieved in 90% of patients. The best response was stable disease in 8 pts for an average of 5.5 m (range 1.6-13.2 m). Conclusions: Intermittent administration of high dose oral V in combination with F is feasible and achieves target serum levels > 2.5 μM associated with in vitro synergy. V concentrations higher than previously reported with oral dosing were achieved without undue toxicity. The recommended phase II dose is V 800 mg once daily for 3 d (d 1- 3) with F on d 2 given as 30 mg/m2 over 30 min followed by 30 mg/m2 over 4 h, every 14 d. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck
P0826 : Effectiveness of simeprevir (SMV)-containing regimens among patients with chronic hepatitis C virus (HCV) in various us practice settings: Interim analysis of the sonet study
Authors: I. Alam, R. Manch, S. Naggie, R. Reindollar, J. Slim, A. Prabhakar, K. Lauwers, C. Donovan, N. Tandon, J. Forlenza, K. Brown
Journal: Journal of Hepatology (2015)
Functional In Vitro Studies Of Buffy Coat Pooled Platelets Cryopreserved In Dimethyl-Sulphoxide With a New System
Authors: Mariasanta Napolitano, Lucio Lo Coco, Giorgia Saccullo, Giovanni De Francisci, Amalia Reina, Debora Allegro, Raffaella Fadda, Diana Di Liberto, Salvatrice Mancuso, Luca Valore, Gianpaolo Vaccarella, Rosalia Agliastro, Francesco Dieli, Sergio Siragusa
Journal: Blood (2013)
Phase 2 Study of Monotherapy Galunisertib (LY2157299 Monohydrate) in Very Low-, Low-, and Intermediate-Risk Patients with Myelodysplastic Syndromes
Authors: David Valcarcel, Amit Verma, Uwe Platzbecker, Valeria Santini, Aristoteles Giagounidis, María Díez-Campelo, Jan Janssen, Richard F. Schlenk, Gianluca Gaidano, Jaime Perez de Oteyza, Ann L Cleverly, Alan Y Chiang, Michael Lahn, Durisala Desiaih, Susan C. Guba, Alan F. List, Rami S. Komrokji
Journal: Blood (2015)
Molecular Responses At 3 Months Are Associated With a Better Subsequent Molecular response and Outcome In Children and Adolescents With CML In Chronic Phase: Results Of a Retrospective Analysis From The French Glivec Phase 4 Study
Authors: Frédéric Millot, Joelle Guilhot, André Baruchel, Arnaud Petit, Thierry Leblanc, Yves Bertrand, Françoise Mazingue, Patrick Lutz, Cécile Vérité, Christian Berthou, Claire Galambrun, Nicolas Sirvent, Karima Yacouben, Pascal Chastagner, Virginie Gandemer, Yves Reguerre, Gérard Couillaud, Jean-Michel Cayuela
Journal: Blood (2013)
A nationwide survey of common viral infections in childhood among patients with primary immunodeficiency diseases
Authors: Etsuro Nanishi, Takayuki Hoshina, Hidetoshi Takada, Masataka Ishimura, Hisanori Nishio, Takahiro Uehara, Yumi Mizuno, Shunji Hasegawa, Shouichi Ohga, Masayoshi Nagao, Maiko Igarashi, Shuhei Yajima, Yoshio Kusumoto, Noriko Onishi, Yoji Sasahara, Takahiro Yasumi, Toshio Heike, Toshiro Hara, Chie Kobayashi, Takashi Ishige, Kanako Kudo, Kyouko Suzuki, Shohei Ogata, Masako Kikuchi, Yachiyo Kurihara, Ryo Niiya, Tomohiro Katsuta, Yutaka Saikawa, Hisao Yoshida, Yuko Ishizaki, Akira Hayakawa, Toshihiko Shirakawa, Toshihiko Mori, Yutaka Suzuki, Hideo Tsuda, Tomoko Sato, Tomoko Waragai, Satoru Kumaki, Osamu Komiyama, Masumi Seto, Ryo Kadoya, Noriko Ohbuchi, Hiroko Kozan, Hiroyuki Shimizu, Tomoyuki Imagawa, Yoshiyuki Yamada, Takuya Hara, Takuro Ohno, Eiji Ota, Hiroyuki Toda
Journal: Journal of Infection (2016)
Abstract 4357: Harnessing system xCT- to target mutant p53 cancer cells
Authors: David SH Liu, Matthew Read, Klas G. Wiman, Sue Haupt, Cuong P. Duong, Lars Abrahmsen, Ygal Haupt, Nicholas J. Clemons, Wayne A. Phillips
Journal: Cancer Research (2016)

Abstract p53, a critical tumour suppressor is mutated in over half of all human cancers. The loss of wild-type p53 activity together with oncogenic gain-of-function, secondary to aberrant accumulation of mutant p53 protein frequently results in aggressive tumour phenotype, resistance to conventional therapies and poor survival. Therefore, effective therapeutic strategies to target mutant p53 cancer cells remain an urgent and unmet medical need. Here we show that mutant p53 accumulation across multiple tumour types represses the transcription of SLC7A11, a key component of system xCT-, resulting in reduced cystine uptake, lowering endogenous glutathione stores and predisposing cells to oxidative damage. Notably, genetic knockdown or pharmacological inhibition (erastin and sulfasalazine) of system xCT- preferentially induces apoptosis in cancer cells with mutant p53 accumulation. Moreover, we found that APR-246 (PRIMA-1met), a first-in-class reactivator of mutant p53 currently in early clinical trials, depletes cellular glutathione and induces significantly higher amounts of reactive oxygen species in mutant p53 cancer cells compared with normal cells. This leads to lipid peroxidation of mitochondrial membranes and the release of matrix contents, culminating in apoptotic cell death. Conversely, APR-246-induced cytotoxicity could be rescued by cysteine or glutathione replacement, or with lipophilic antioxidants. In extension, we identified and functionally validated SLC7A11 expression as a specific predictive biomarker for APR-246. Importantly, we demonstrate that antagonising system xCT- activity in combination with APR-246 selectively and synergistically inhibit mutant p53 cancer cells. Together, our findings propose that accumulation of mutant p53 protein in cancer cells, through its repressive effects on SLC7A11 expression, creates an ‘Achilles heel’ that can be targeted by further perturbations of the glutathione pathway. Citation Format: David SH Liu, Matthew Read, Klas G. Wiman, Sue Haupt, Cuong P. Duong, Lars Abrahmsen, Ygal Haupt, Nicholas J. Clemons, Wayne A. Phillips. Harnessing system xCT- to target mutant p53 cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4357.
Abstract 4543: Substrate trapping proteomics reveals novel mechanism for regulation of mTORC1 signaling by βTrCP-FNIP1/2-FLCN axis
Authors: Tai Young Kim, Jee Yun Chang, Jin Mo Ku, Se Hyang Hong, ji Hye Kim, Hyeong Sim Choi, Kangwook Lee, Myeong-Sun Kim, Sang Mi Woo, Michael B. Major, Seong-Gyu Ko
Journal: Cancer Research (2016)

Abstract Defining the full complement of substrates for each ubiquitin ligase remains an important challenge. Improvements in mass spectrometry instrumentation and computation and in protein biochemistry methods have resulted in several new methods for ubiquitin ligase substrate identification. Here we used the parallel adapter capture (PAC) proteomics approach to study βTrCP2, a substrate adaptor for the SKP1-CUL1-F-box (SCF) E3 ubiquitin ligase complex. The processivity of the ubiquitylation reaction necessitates transient physical interactions between βTrCP2 and its substrates, thus making biochemical purification of FBXW11-bound substrates difficult. Using the PAC-based approach, we inhibited the proteasome to “trap” ubiquitylated substrates on the SCF (βTrCP2) E3 complex. Comparative mass spectrometry analysis of immunopurified βTrCP2 protein complexes before and after proteasome inhibition revealed 21 known and 23 putatively novel substrates. Interestingly, many novel substrates for βTrCP2, including TBC1D4, HCFC1, DENND4C, FNIP1, and FLCN are related to cell metabolism. TBC1D4 encodes a GTPase activating protein for the small GTPase Rab that controls insulin-dependent trafficking of the GLUT4 glucose transporter in adipocytes. DENND4C acts as a guanine nucleotide exchange factor for Rab10 and its activity is required for insulin-stimulated GLUT4 translocation to plasma membrane in adipocytes. HCFC1 is a member of the host cell factor family, affecting gluconeogenesis by modulating PGC-1α stability. These suggest βTrCP2 might play important roles in glucose homeostasis by regulating stability of several different target proteins. Here, in focused study, we found that βTrCP1/2 bound, polyubiquitylated, and destabilized FNIP1, FLCN interacting protein 1. We further demonstrated that FNIP1 degradation was promoted by AMPK activation after glucose depletion and expression of a degradation-resistant FNIP1 mutant results in sustained activation of mTORC1 signaling. Hence, our findings reveal that βTrCP1/2 is involved in nutrient sensing through the AMPK-FLCN-FNIP1 and mTORC1 signaling pathways. Citation Format: Tai Young Kim, Jee Yun Chang, Jin Mo Ku, Se Hyang Hong, ji Hye Kim, Hyeong Sim Choi, Kangwook Lee, Myeong-Sun Kim, Sang Mi Woo, Michael B. Major, Seong-Gyu Ko. Substrate trapping proteomics reveals novel mechanism for regulation of mTORC1 signaling by βTrCP-FNIP1/2-FLCN axis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4543.
Impact Of TET2 Deficiency On MPN Harboring JAK2V617F Mutation
Authors: Takuro Kameda, Kotaro Shide, Masaaki Sekine, Ayako Kamiunten, Tomonori Hidaka, Yoko Kubuki, Akira Kitanaka, Kousuke Marutsuka, Kazuya Shimoda
Journal: Blood (2013)
Cell-Intrinsic and Cell-Extrinsic Involvement Of C/EBPβ In The Regulation Of Hematopoietic Stem Cells
Authors: Akihiro Tamura, Hideyo Hirai, Yoshihiro Hayashi, Asumi Yokota, Atsushi Sato, Satoshi Yoshioka, Masaki Iwasa, Eishi Ashihara, Yasuo Miura, Taira Maekawa
Journal: Blood (2013)
Abstract 2534: Low glucose and hypoxia environment promote the enrichment of liver cancer stem cells
Authors: Chih Chung Lai, Tsu-Hsiang Shia, Yu-Peng Liu, Chia-Hung Yen
Journal: Cancer Research (2016)

Abstract Cancer stem cells (CSCs), a subpopulation possess tumor initiation and self-renewal capacity, are responsible for recurrence, metastases and drug resistance. Thus, it is important to understand their biology for identification of new therapeutic approaches. Liver surgery and/or transarterial (chemo) embolization (TAE/TACE) therapy usually generate a microenvironment that fosters aggressive tumor recurrence. These areas are characterized by chronic hypoxia and possibly low glucose concentration. Here, we tested the hypothesis that whether hypoxia along with low glucose environment promote the expansion of CSC population in HCC cells. We cultured human liver cancer cell line-Huh7 cells in normoxia or hypoxia condition with high or low glucose medium. The EMT markers (N-cadherin and Vimentin) but not stemness genes (CD44 and CD133) were upregulated in hypoxia condition. However, all genes were significantly induced under low glucose/hypoxia condition. In addition, results from sphere assay showed that low glucose/hypoxia condition dramatically improved the sphere formation ability of Huh7 cells, while low glucose or hypoxia along cannot promote sphere formation. Moreover, Huh7 cells cultured in low glucose/hypoxia condition displayed a lower sensitivity to cisplatin and doxorubicin treatment compared to cells maintained in high glucose/normoxia condition. Therefore, our findings suggested that low glucose concentration and hypoxia environment remarkably promote the enrichment of liver CSCs which could be useful for developing novel therapeutic modalities. Citation Format: Chih Chung Lai, Tsu-Hsiang Shia, Yu-Peng Liu, Chia-Hung Yen. Low glucose and hypoxia environment promote the enrichment of liver cancer stem cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2534.
Cancer-Associated Fibroblasts in Pancreatic Cancer Are Reprogrammed by Tumor-Induced Alterations in Genomic DNA Methylation
Authors: Qian Xiao, Donger Zhou, Agnieszka A. Rucki, Jamila Williams, Jiaojiao Zhou, Guanglan Mo, Adrian Murphy, Kenji Fujiwara, Jennifer Kleponis, Bulent Salman, Christopher L. Wolfgang, Robert A. Anders, Shu Zheng, Elizabeth M. Jaffee, Lei Zheng
Journal: Cancer Research (2016)

Abstract Stromal fibrosis is a prominent histologic characteristic of pancreatic ductal adenocarcinoma (PDAC), but how stromal fibroblasts are regulated in the tumor microenvironment (TME) to support tumor growth is largely unknown. Here we show that PDAC cells can induce DNA methylation in cancer-associated fibroblasts (CAF). Upon direct contact with PDAC cells, DNA methylation of SOCS1 and other genes is induced in mesenchymal stem cells or in CAF that lack SOCS1 methylation at baseline. Silencing or decitabine treatment to block the DNA methylation enzyme DNMT1 inhibited methylation of SOCS1. In contrast, SOCS1 gene methylation and downregulation in CAF activated STAT3 and induced insulin-like growth factor-1 expression to support PDAC cell growth. Moreover, CAF facilitated methylation-dependent growth of PDAC tumor xenografts in mice. The ability of patient-derived CAF with SOCS1 methylation to promote PDAC growth was more robust than CAF without SOCS1 methylation. Overall, our results reveal how PDAC cells can reprogram CAF to modify tumor–stromal interactions in the TME, which promote malignant growth and progression. Cancer Res; 76(18); 5395–404. ©2016 AACR.
Abstract 708: Defensin-alpha 6 (DEFA6) as a protumorigenic functionin vitroand prognostic marker in colorectal cancer
Authors: Dongjun Jeong, Hyungjoo Kim, Seunghyun Oh, Seona Ban, Sanghee Ji, Han Jo Kim, Tae Sung Ahn, Tae Hyun Kim, Hyog Young Kwon, Seob Jeon, Sang Byung Bae, Chang-Jin Kim, Moon Soo Lee, Moo-Jun Baek
Journal: Cancer Research (2016)

Abstract Objective DEFA6 also known as human alpha defensing 6 (HD6) is a member of the alpha defensins family that defends the host against bacteria and viruses. Expression of DEFA6 is enhanced in colorectal cancer tissue and cells. The mechanism and function of DEFA6 have not been reported to play an important role in carcinogenesis and cancer progression. The goal of this study was to evaluate the protumorigenic functions of DEFA6 in the colorectal cancer cell line and to evaluate the clinical significance of DEFA6 expression in colorectal cancer patients. Methods DEFA6 was highly expressed in colorectal cancer cell lines. Colorectal cancer cell, HCT116, expressing high level of DEFA6 was used for the biological roles of DEFA6 by siRNA transfection. The protumorigenic functions of DEFA6 was evaluated by MTT assay, migration and invasion transwell assay and plate colony forming assay. DEFA6 expression was investigated by immunohistochemistry in 60 cases of colorectal cancer tissue and the association of DEFA6 expression was correlated with patient's survival. Results Immunohistochemistry analysis showed that the DEFA6 protein was expressed higher in death group (survival &amp;lt;5 years) than survival group (survival &amp;gt;5 years), (p = 0.02). The HCT116 of knockdowned DEFA6 by siRNA showed significant decrease in proliferation by MTT assay (p&amp;lt;0.05) and plate colony forming assay (p = 0.00). Also, the ability of migration and invasion was significantly reduced in DEFA6 knockdowned HCT116 compared to control HCT116 cell (both, p&amp;lt;0.05). Conclusion DEFA6 plays important roles in invasion and migration of colorectal cancer cell according to the functional study. As patient's survival mostly depends on the migration and invasion of the tumor cells, the high expression of DEFA6 in colorectal cancer is associated with patient's survival and could be a good prognostic marker. Citation Format: Dongjun Jeong, Hyungjoo Kim, Seunghyun Oh, Seona Ban, Sanghee Ji, Han Jo Kim, Tae Sung Ahn, Tae Hyun Kim, Hyog Young Kwon, Seob Jeon, Sang Byung Bae, Chang-Jin Kim, Moon Soo Lee, Moo-Jun Baek. Defensin-alpha 6 (DEFA6) as a protumorigenic function in vitro and prognostic marker in colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 708.
Donor Requirements For CD4+CD25+FoxP3+ Regulatory T Cells Capable Of Suppressing CD4+ and CD8+ Conventional T Cell Proliferation and Graft Versus Host Disease
Authors: Antonio Pierini, Lucrezia Colonna, Maite Alvarez, Dominik Schneidawind, Byung-Su Kim, Jeanette Baker, Robert Negrin
Journal: Blood (2013)
Abstract 2818: An unbiased tumor cell panel profiling method to identify drug-drug interactions reveals synergy between the CDK4 and CDK 6 inhibitor abemaciclib and the Raf dimer and pan-Raf inhibitor LY3009120 in Ras mutant cancers
Authors: Xueqian Gong, Wenjuan Wu, Li-Chun Chio, Susan Pratt, Constance King, Yue Webster, Maria Jose Lallena, Karsten Boehnke, Raquel Torres, Philip Iversen, Christoph Reinhard, Shih-Hsun Chen, Richard Bechmann, Sheng-Bin Peng, Sean Buchanan
Journal: Cancer Research (2016)

Abstract Drug sensitivity profiling across genomically characterized panels of tumor cells can identify the molecular determinants of drug response. By testing compound combinations in an unbiased format, the same methodology can be used to identify the genomic context of drug-drug synergy. Based on this principle, we developed an unbiased combination screening protocol to identify synergistic interactions with LY3009120, a novel Raf dimer inhibitor that inhibits all three Raf isoforms (Peng et al. 2015, Cancer Cell 28:384-98). Inhibitors of the Ras-MAPK pathway have proven very effective in the treatment of BRAF-mutant melanoma but are, in general, only partially effective in the treatment of BRAF-mutant colorectal cancer and Ras mutant cancers. LY3009120 combined with various compounds was screened across panels of genomically characterized tumor cells. These screens identified a strong synergy with abemaciclib, an inhibitor of cyclin dependent kinases 4 and 6 (CDK4 and CDK6). Statistical analysis of effects in over 500 cancer cell lines showed that mutations in BRAF or Ras family genes were strongly associated with sensitivity to this combination. Strong synergy was observed in skin, colorectal, lung and pancreatic cancers with Ras/Raf mutations, but was also observed in various cancer cells wild type for Ras pathway genes. This included tumor types sensitive to single agent abemaciclib, such as mantle cell lymphoma, ER+ breast cancers, certain leukemias, squamous non-small cell lung cancer, and/or lung cancer with receptor tyrosine kinase activation. In vitro and in vivo analyses of the effects of the combination treatment on signaling pathways in KRAS mutant cancers led to potential mechanistic explanations for the differing efficacy of the combination, which manifests as regression of tumor xenografts in rodent models. Citation Format: Xueqian Gong, Wenjuan Wu, Li-Chun Chio, Susan Pratt, Constance King, Yue Webster, Maria Jose Lallena, Karsten Boehnke, Raquel Torres, Philip Iversen, Christoph Reinhard, Shih-Hsun Chen, Richard Bechmann, Sheng-Bin Peng, Sean Buchanan. An unbiased tumor cell panel profiling method to identify drug-drug interactions reveals synergy between the CDK4 and CDK 6 inhibitor abemaciclib and the Raf dimer and pan-Raf inhibitor LY3009120 in Ras mutant cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2818.
Abstract 5067: Casein kinase 2 alpha phosphorylation of cortactin governs actin cytoskeletal regulation of invadopodia function
Authors: Steven M. Markwell, Amanda Gatesman Ammer, Erik T. Interval, Dorothy A. Schafer, River A. Hames, Scott A. Weed
Journal: Cancer Research (2016)

Abstract Malregulation of signal transduction events controlling cortical actin cytoskeleton dynamics is responsible for to enhancing tumor cell motility and invasion. The actin-binding protein cortactin facilitates branched actin network formation through activation of the actin related protein (Arp) 2/3 complex. Increased cortactin expression due to gene amplification is observed in many cancers, corresponding with increased tumor progression and poor patient outcome. In many cancer types, elevated Arp2/3 complex activation is responsible for driving increased migration and extracellular matrix (ECM) degradation by governing invadopodia formation and activity. While cortactin-mediated activation of Arp2/3 complex has been well established, the objective of this study is to identify upstream signaling pathways responsible for modulating the interaction between cortactin and Arp2/3 complex in invasive carcinoma cells. We have determined that casein kinase (CK) 2α is responsible for disrupting the ability of cortactin to bind and/or activate Arp2/3 complex. CK2α directly phosphorylates cortactin at a conserved threonine 24 (T24) adjacent to the canonical Arp2/3 binding motif in the cortactin amino-terminal acidic (NTA) domain. CK2α phosphorylation of cortactin T24 impairs the ability of cortactin to activate Arp2/3 actin nucleation as determined by spectrofluorometric analysis. Decreased invadopodia formation and ECM degradation activity is observed in head and neck squamous cell carcinoma (HNSCC) cells with shRNA-mediated CK2α knockdown, expression of a CK2α phosphorylation-null cortactin mutant (T24A), and with treatment of the Phase I CK2α inhibitor CX-4945 (Silmitasertib). Collectively, these data suggest that CK2α-mediated cortactin phosphorylation at T24 is a critical event in regulating the interaction with Arp2/3 complex, identifying a key anti-invasive mechanism impacted by targeted anti-CK2α therapeutics. Citation Format: Steven M. Markwell, Amanda Gatesman Ammer, Erik T. Interval, Dorothy A. Schafer, River A. Hames, Scott A. Weed. Casein kinase 2 alpha phosphorylation of cortactin governs actin cytoskeletal regulation of invadopodia function. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5067.