tbuckley/cabot-search huggingface dataset:
P36 Injections of intravenous contrast for computerised tomography scans precipitate migraines in hereditary haemorrhagic telangiectasia subjects at risk of paradoxical emboli: implications for right-to-left shunt risks
Authors: T Patel, A Elphick, JE Jackson, CL Shovlin
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> Migraine headaches commonly affect people with pulmonary arteriovenous malformations (PAVMs) that provide right-to-left shunts. The majority of PAVMs are due to underlying hereditary haemorrhagic telangiectasia (HHT). In our clinical practice, patients occasionally reported acute precipitation of migraine headaches following injection of technetium-labelled albumin macroaggregates for nuclear medicine scans. Our goal was to evaluate if injection of intravenous particles may provoke migraines in the cohort. <h3>Methods</h3> Self-reported migraine features and exacerbations were examined in HHT subjects with and without pulmonary AVMs, for a series of noninvasive and invasive investigations, using an unbiased online survey. With ethical approval, the study recruited between August 2013–April 2015. Data were downloaded in December 2015 for analysis using STATA IC v12 and GraphPad Prism. Two group comparisons were performed using Mann Whitney or Fisher’s exact test (for proportions). Multiple groups were compared using Kruskal Wallis with Dunn’s multiple comparison test. <h3>Results</h3> 166 subjects were classified as having both HHT and migraines. HHT subjects with migraines were more likely to have pulmonary AVMs (p &lt; 0.0001). Pulse oximetry, x-rays, ultrasound and computerised tomography (CT) scans without intravenous contrast medium rarely, if ever, provoked migraines, but unenhanced magnetic resonance imaging (MRI) was reported to exacerbate migraines by 14/124 (11.2%) subjects. 114 had both enhanced and unenhanced CT examinations: studies with contrast media were more commonly reported to start (9/114 [7.8%]), and/or worsen migraines (18/114 [15.7%]) compared to those undertaken without contrast medium (p &lt; 0.01), or after simple blood tests (p &lt; 0.05). Additionally, migraine exacerbation was reported by 9/90 (10%) after contrast echocardiography, 2/44 (4.5%) after nuclear medicine scans, and 10/154 (6.5%) after blood tests. <h3>Conclusions</h3> In this population, MRI studies, blood tests, contrast echocardiograms, and intravenous injection of iodinated contrast medium associated with CT examinations were reported to provoke or exacerbate migraines. Since air emboli are recognised to complicate intravenous injections, particularly following pressurised pump injections of CT scan contrast, evaluation of migraines as a potential read-out for paradoxical emboli is recommended. In the meantime, for people with HHT and migraines, pre-test counselling may helpfully include advice to bring migraine preventers or treatments to help alleviate symptoms promptly.
Clofarabine Combinations in Adults with Refractory/Relapsed Acute Lymphoblastic Leukemia (ALL): A GRAALL Report
Authors: Arnaud Pigneux, Mathieu Sauvezie, Norbert Vey, Emmanuel Raffoux, Ambroise Marcais, Françoise Huguet, Philippe Rousselot, Jean Pierre Marolleau, Stéphane Leprêtre, Pascal Turlure, Patrice Chevallier, Mathilde Hunault, Caroline Bonmati, Thomas Cluzeau, Thibaut Leguay, Norbert Ifrah, Herve Dombret
Journal: Blood (2011)
Didox Induced Apoptosis Occurs by Inhibiting DNA Synthesis and Repair Via Down-Regulation of Ribonucleotide Reductase M1 in Multiple Myeloma (MM).
Authors: Noopur Raje, Shaji Kumar, Teru Hideshima, Kenji Ishitsuka, Hiroshi Yasui, Norihiko Shiraishi, Tanyel Kiziltepe, Shweta Chhetri, Nikhil C. Munshi, Kenneth C. Anderson
Journal: Blood (2005)
Combination of Bortezomib and Dexamethasone (VD) or Bortezomib, Adriamycine and Dexamethasone (PAD) Followed by High Dose Therapy and Peripheral Blood Stem Cell Transplantation in First-Line Treatment of T(4;14) Multiple Myeloma : a Prospective Study of the MAG Group.
Authors: Lionel Karlin, David Ghez, Marie-Olivia Chandesris, Sylvain Choquet, Margaret Macro, Didier Bouscary, Sophie Cereja, Marion Malphettes, Bouchra Asli, Vincent Levy, Jean Soulier, Jean-Paul Fermand, Bertrand Arnulf
Journal: Blood (2009)
Are Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) Occurring during the Course of Lymphoma (Ly) Always Therapy Related?
Authors: Camille Bigenwald, Stephanie Harel, Florian Chevillon, Damien Roos-Weil, Olivier A. Bernard, Sandy Amorim, Pauline Brice, Ades Lionel, Anne Marie Nloga, Marie Sébert, Thorsten Braun, Virginie Eclache, Catherine Thieblemont, Pierre Fenaux
Journal: Blood (2015)
Abstract B21: Brd4 modulates S-phase checkpoint response and sensitizes ovarian cancer cells to ATR inhibition
Authors: Jingwen Zhang, Huawei Chen, Austin Dulak
Journal: Clinical Cancer Research (2017)

Abstract The BET (bromodomain and extra terminal domain) family proteins function as chromatin readers through interactions with acetylated lysine residues on both histones and transcription factors. BRD4 is the most well-studied member of this group that promotes tumorigenesis by regulating expression of core transcriptional programs; however, the role of Brd4 in other cellular processes is not entirely clear. Here, we show using small molecule inhibition of the BET proteins that Brd4 is required to maintain S-phase checkpoint signaling. Treatment of high-grade serous ovarian and osteosarcoma cancer cell lines with BET inhibitors, AZD5153 and JQ1, results in the accumulation of gH2AX and 53BP1 foci formation, which is suggestive of elevated DNA damage levels. The induction of DNA damage caused by both inhibitors corresponds with cell cycle arrest at the G1/S boundary. Displacement of Brd4 in cell lines under intrinsic or exogenous replication stress led to a time-dependent reduction in phospho-Chk1 first detected within 30 minutes of AZD5153 treatment in U2OS cells. The decrease in Chk1 phosphorylation was observed without a concomitant decrease in total Chk1, and this was not replicated by treatment with pan-transcriptional inhibitors, suggesting a non-transcriptional mechanism linked to Brd4. Furthermore, Brd4 interacts with core DNA replication machinery during S-phase and inhibition of Brd4 leads to aberrant DNA replication without decreasing ATR phosphorylation. Consistent with a role in S-phase signaling, Brd4 inhibition sensitizes replicating cells to replication stress-inducing agents. Finally, we observed that ovarian cancer cell lines are highly-sensitive to the combination of Brd4 and ATR (AZD6738) inhibitors. Concurrent treatment with AZD5153 and AZD6738 induces DNA damage and apoptosis in a synergistic manner. Together, these findings highlight a novel function for Brd4 and provide evidence to support further evaluation of Brd4i combinations with DNA damage repair agents. Citation Format: Jingwen Zhang, Huawei Chen, Austin Dulak. Brd4 modulates S-phase checkpoint response and sensitizes ovarian cancer cells to ATR inhibition. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B21.
Outcome of Hematopoietic Cell Transplant from HLA-Matched Siblings Compared to a Volunteer Unrelated Donors Matched for HLA-A, B, C, DRB1, and DQB1 Alleles.
Authors: Ann Woolfrey, Theodore Gooley, Mari Malkki, John A. Hansen, Paul J. Martin, Stephanie J. Lee, Frederick R. Appelbaum, John M. Pagel, Effie W. Petersdorf
Journal: Blood (2007)
Patients’ Peripheral Blood as a Possible Source of Donor-Derived NK Cells for Ex Vivo Expansion and Genetic Modification for Post-Transplant Cellular Immunotherapy In Cord Blood Recipients
Authors: Chihaya Imai, Sakiko Yoshida, Takayuki Takachi, Masaru Imamura, Ryosuke Hosokai, Haruko Iwabuchi, Makoto Uchiyama, Keiko Asami, Atsushi Ogawa, Akihiro Watanabe
Journal: Blood (2010)
Promyelocytic extracellular chromatin exacerbates coagulation and fibrinolysis in acute promyelocytic leukemia
Authors: Muhua Cao, Tao Li, Zhangxiu He, Lixiu Wang, Xiaoyan Yang, Yan Kou, Lili Zou, Xue Dong, Valerie A. Novakovic, Yayan Bi, Junjie Kou, Bo Yu, Shaohong Fang, Jinghua Wang, Jin Zhou, Jialan Shi
Journal: Blood (2017)
P2.06-025 DREAM - A Phase 2 Trial of DuRvalumab with First Line chEmotherApy in Mesothelioma with a Safety Run In
Authors: Anna Nowak, Peey-Sei Kok, Ann Livingstone, Willem Joost Lesterhuis, Sonia Yip, Mark Donoghoe, Wei-Sen Lam, Martin Stockler
Journal: Journal of Thoracic Oncology (2017)
Impact of Regulatory T Cells on Antigen Specific T Cell Response Using Recombinant Chimeric T Cell Receptors In Vivo.
Authors: David M. Kofler, Markus Chmielewski, Heike Koehler, Tobias Riet, Patrick Schmidt, Gunter Rappl, Andreas Hombach, Michael Hallek, Clemens M. Wendtner, Hinrich Abken
Journal: Blood (2006)
P3.03-009 Role of microRNAs as Biomarkers of Malignant Mesothelioma in Patients with Pleural Effusion
Authors: Alessandro Palleschi, Valentina Bollati, Chiara Favero, Carolina Mensi, Claudia Bareggi, Arianna Rimessi, Davide Tosi, Paolo Mendogni, Mario Nosotti
Journal: Journal of Thoracic Oncology (2017)
The role of KRAS, BRAF, and PI3K mutations as markers of resistance to cetuximab in metastatic colorectal cancer.
Authors: A. Passardi, P. Ulivi, M. Valgiusti, E. Scarpi, R. Moscati, E. Chiadini, P. Rosetti, L. Saragoni, L. Capelli, A. Casadei Gardini, A. Ragazzini, M. Monti, S. Calpona, W. Zoli, C. Milandri, L. Frassineti
Journal: Journal of Clinical Oncology (2011)

3603 Background: KRAS mutations negatively affect outcome after cetuximab (CTX) in metastatic colorectal cancer (mCRC). As only 20% of KRAS wild-type (WT) patients respond it is possible that other mutations, constitutively activating the EGFR pathway, are present in the non-responding WT. We retrospectively correlated KRAS, BRAF and PI3K mutational status with the clinical outcome of 64 mCRC patients treated with CTX plus chemotherapy. Methods: DNA was extracted from 5 mM paraffin-embedded sections containing at least 50% of tumoral cells, derived from primary or metastatic lesions. Exon 2 of KRAS and exon 15 of BRAF were amplified by PCR and analysed by direct sequencing. PIK3CA status was analysed by Pyrosequencing. A two-sided Fisher's exact test was used to evaluate the association between mutations and objective response (OR). Progression-free survival (PFS) was estimated by Kaplan-Meier method and curves were compared by log-rank test. Hazard ratios (HR) were estimated according to Cox multiple regression model. Results: Patient characteristics were as follows: Male/Female = 35/29; primary site: rectum/colon =13/51. KRAS, BRAF and PI3K mutations were present in 28.1%, 21.3% and 15.1% of CRC lesions, respectively. KRAS WT/MUT was associated with OR 28.3/22.2% (p=0.75), median PFS 5.1 (95% CI 3.3-6.2)/3.1 months (95%CI 2.3-5.5), p=0.85. BRAF WT/MUT was associated with OR 33.3/7.7% (p=0.08), PFS 5.1 (95% CI 2.9-6.5)/3.4 months (95%CI 1.4-5.1), p<0.01. PI3K WT/MUT was associated with OR 31.1/12.5% (p=0.41), PFS 5.3(95% CI 3.6-6.5)/2.2 months (95% CI 1.1-3.3), p<0.01. PFS (95% CI) was increasingly worse for patients with tumors harboring none, 1, or ≥ 2 molecular alteration(s): 5.5 (2.7-8.7), 3.5 (2.3-5.5), 2.1 months (1.0-3.9), respectively, p<0.01. Moreover, the multivariate analysis of PFS indicated BRAF and PI3K as potential independent predictors of clinical benefit: HR (95% CI) 2.74 (1.37-5.45), p<0.01 and 3.57 (1.45-8.80), p<0.01, respectively. Conclusions: Our results seem to confirm that comprehensive molecular dissection of the EGFR signaling pathways should be considered to better select mCRC patients for CTX based therapies.
P3.05-004 Psycho-Social Function and Caregiver's Burden in Patients with Advanced Lung Cancer
Authors: Claudia Cormio, Daniela Bafunno, Annamaria Catino, Domenico Galetta, Andrea Misino, Elisabetta Sara Montagna, Donata Ricci, Patrizia Petrillo, Antonio Fabio Logroscino
Journal: Journal of Thoracic Oncology (2017)
Treatment with Erythropoietin and G-CSF Improves Survival in MDS Patients with Low Transfusion Need.
Authors: Martin Jädersten, Luca Malcovati, Ingunn Dybedal, Matteo Giovanni Della Porta, Rosangela Invernizzi, Scott M. Montgomery, Cristiana Pascutto, Anna Porwit-MacDonald, Mario Cazzola, Eva Hellström-Lindberg
Journal: Blood (2006)
P2.04-026 Expression Patterns of PD-L1 in Esophageal Adenocarcinomas: Comparison between Primary Tumors and Metastases
Authors: Bastian Dislich, Alexandra Stein, Jose Galvan, Sabina Berezowska, Christian Seiler, Dino Kroell, Rupert Langer
Journal: Journal of Thoracic Oncology (2017)
Phase IIa Study of the Anti-CXCL12/SDF-1 Spiegelmer® Nox-A12 Alone and Combined with Bendamustine/Rituximab in Patients with Relapsed Chronic Lymphocytic Leukemia (CLL)
Authors: Marco Gobbi, Federico Caligaris-Cappio, Marco Montillo, Stephanie Vauléon, Stefan Zöllner, Thomas Dümmler, Anna Kruschinski, Frank Fliegert
Journal: Blood (2012)
The Mantle Cell Lymphoma International Prognostic Index (MIPI) at Diagnosis Is Associated with Survival of Mantle Cell Lymphoma Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation.
Authors: Lihua Pan, Katherine A Guthrie, Brian G. Till, Oliver W. Press, John M. Pagel, Stephen Petersdorf, William Bensinger, Leona Holmberg, David G. Maloney, Ajay Gopal
Journal: Blood (2008)
Nuclear Localization of the NuMA-RARα/RXRα Complex Is Necessary for Leukemogenesis in hCG-NuMA-RARα Transgenic Mice.
Authors: Mahadeo A. Sukhai, Mariam Thomas, Yali Xuan, Soheila A. Hamadanizadeh, Rikki R. Bharadwaj, Andre Schuh, Richard A. Wells, Suzanne Kamel-Reid
Journal: Blood (2006)
Comparison of Allogeneic Hematopoietic Cell Transplantation (HCT) after Nonmyeloablative Conditioning with HLA-Matched Related (MRD), Unrelated (URD), and Related Haploidentical (Haplo) Donors for Relapsed or Refractory Hodgkin Lymphoma (HL).
Authors: Lauri Burroughs, Paul O’Donnell, Brenda M. Sandmaier, Barry Storer, Leo Luznik, Heather Symons, Michael Maris, Karl G. Blume, Dietger W. Niederwieser, Benedetto Bruno, Richard T. Maziarz, Michael Pulsipher, Finn Petersen, Peter A. McSweeney, Thomas Chauncey, Edward Agura, James C. Wade, Rainer F. Storb, Ephraim J. Fuchs, David G. Maloney
Journal: Blood (2007)
Inhibition of αvβ5 Integrin Attenuates Vascular Permeability and Protects against Renal Ischemia-Reperfusion Injury
Authors: Amy McCurley, Stella Alimperti, Silvia B. Campos-Bilderback, Ruben M. Sandoval, Jenna E. Calvino, Taylor L. Reynolds, Catherine Quigley, Joshua W. Mugford, William J. Polacheck, Ivan G. Gomez, Jennifer Dovey, Graham Marsh, Angela Huang, Fang Qian, Paul H. Weinreb, Brian M. Dolinski, Shaun Moore, Jeremy S. Duffield, Christopher S. Chen, Bruce A. Molitoris, Shelia M. Violette, Michael A. Crackower
Journal: Journal of the American Society of Nephrology (2017)

Ischemia-reperfusion injury (IRI) is a leading cause of AKI. This common clinical complication lacks effective therapies and can lead to the development of CKD. The α v β 5 integrin may have an important role in acute injury, including septic shock and acute lung injury. To examine its function in AKI, we utilized a specific function-blocking antibody to inhibit α v β 5 in a rat model of renal IRI. Pretreatment with this anti- α v β 5 antibody significantly reduced serum creatinine levels, diminished renal damage detected by histopathologic evaluation, and decreased levels of injury biomarkers. Notably, therapeutic treatment with the α v β 5 antibody 8 hours after IRI also provided protection from injury. Global gene expression profiling of post-ischemic kidneys showed that α v β 5 inhibition affected established injury markers and induced pathway alterations previously shown to be protective. Intravital imaging of post-ischemic kidneys revealed reduced vascular leak with α v β 5 antibody treatment. Immunostaining for α v β 5 in the kidney detected evident expression in perivascular cells, with negligible expression in the endothelium. Studies in a three-dimensional microfluidics system identified a pericyte-dependent role for α v β 5 in modulating vascular leak. Additional studies showed α v β 5 functions in the adhesion and migration of kidney pericytes in vitro . Initial studies monitoring renal blood flow after IRI did not find significant effects with α v β 5 inhibition; however, future studies should explore the contribution of vasomotor effects. These studies identify a role for α v β 5 in modulating injury-induced renal vascular leak, possibly through effects on pericyte adhesion and migration, and reveal α v β 5 inhibition as a promising therapeutic strategy for AKI.
Favorable Impact of Post-ASCT Consolidative Immunotherapy with RITUXIMAB, rINF-a2b and rIL2 on Overall Survival and Progression-Free Survival in Advanced Stage or Relapsed/Refractory Follicular Lymphoma: Results of a Phase II Study
Authors: Jean-Richard Eveillard, Jean-Christophe Ianotto, Adrian Tempescul, Gaelle Guillerm, Florence Dalbiès, Hussam Saad, Ronan LE Calloc'h, Anaïg Dagorn, Françoise N'go Sack, Christian Berthou
Journal: Blood (2011)
P1.03-001 The Utility of Liquid-Biopsy for Detecting EGFR Mutation in Clinical Practice: 169 Cases in a Single Institution Research Study
Authors: Kentaro Ito, Osamu Hataji, Yuta Suzuki, Haruko Saiki, Tadashi Sakaguchi, Kosuke Hayashi, Yoichi Nishii, Fumiaki Watanabe, Tetsu Kobayashi, Esteban Gabazza, Osamu Taguchi
Journal: Journal of Thoracic Oncology (2017)
Genetic Variation in the Effector Pathways of Cytotoxic T Lymphocytes Influences Alloimmune Reactivities Following Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Haowen Xiao, Yi Luo, Jimin Shi, Yamin Tan, Jingsong He, Wanzhuo Xie, Xiujin Ye, Zhen Cai, Maofang Lin*, He Huang
Journal: Blood (2011)
JCES01.17 A Phase I Dose Expansion Study of Epitinib to Evaluate Efficacy and Safety in EGFR Mutation Positive (EGFRm+) NSCLC Patients with Brain Metastasis
Authors: Qing Zhou, Bin Gan, Qunying Hong, Mengzhao Wang, Xiaoqing Liu, Liwei Yuan, Ye Hua, Hongcan Ren, Weiguo Su, Yi Long Wu
Journal: Journal of Thoracic Oncology (2017)
P1.08-014 Usefulness of Chest CT in Follow-Up of Patients with Completely Resected Lung Cancer
Authors: Jefferson Gross, Juliana Morelato, Marcos Guimarães, Fabio Haddad, João Paulo Medici, Marcus Baranauskas, Helio Carneiro, Maria Luiza Medeiros
Journal: Journal of Thoracic Oncology (2017)
Phase I/II trial of a low-emetic combination of S-1 plus docetaxel (DTX) for advanced non-small cell lung cancer (NSCLC).
Authors: K. Komiyama, K. Kobayashi, S. Minezaki, Y. Uchida, T. Kasai, K. Mori, E. Hoshi, S. Koyama, K. Eguchi, M. Nakayama, K. Kikuchi
Journal: Journal of Clinical Oncology (2011)

e18041 Background: S-1, a novel oral fluorouracil derivative, is active against NSCLC. Previous studies investigating a combination of S-1 plus DTX showed promising efficacy but clinically problematic emesis. We conducted a phase I study to find the maximum tolerated doses (MTD) of bi-weekly administered DTX with oral S-1 for one week, and a phase II study to evaluate the efficacy and toxicity. Methods: Previously treated pts with NSCLC were included. Other eligibility criteria were performance status of 0-1, measurable lesions, age < 75 years, and adequate organic functions were eligible. Pts received S-1 on days 1-7 and DTX on day 1 of each 14-day cycle. Results: Doses of S-1/DTX (mg/m2) in the phase I study portion were escalated as follows: 80/30, 80/35, and 80/40. In the phase I, MTD among 13 patients were S-1 80 mg/m2 with DTX 40 mg/m2. The dose limiting toxicity (DLT) was febrile neutropenia. The recommended doses for the phase II study were S-1 80mg/m2 and DTX 35 mg/m2. A total of 34 pts from 5 institutions were enrolled from Oct. 2009 to Nov .2010. The overall responses were CR 0; PR 9; SD 12; PD 10 and NE 3, resulting in a response rate of 26.5% (95% confidence interval [CI], 11.6-41.3%). The overall disease control rate was 61.8% (95% CI, 45.4-78.1%). Hematologic grade 3/4 toxicities were neutropenia (29.4%), febrile neutropenia (2.9%) and thrombocytopenia (2.9%). In non-haematologic toxicities, 4 patients with grade 2 interstitial pneumonitis were observed. Nine patients experienced grade 1 nausea only for short durations, and there were no grade 2 nausea. There was no emesis in 18 patients (52.9%). Conclusions: The combination of one week S-1 with biweekly DTX is an active regimen with low-emesis for previously treated NSCLC.
Pharmacogenetic Study in Hodgkin’s Lymphomas, Impact of UGT1A1 on Prognosis.
Authors: Vincent Ribrag, Serge Koscielny, Olivier Casasnovas, Cecile Cazeneuve, Pauline Brice, Franck Morschhauser, Jean Gabarre, Marine Divine, Laurent Voillat, Apasia Stamatoullas, Gilbert Lenoir, Gilles Andre Salles
Journal: Blood (2006)
P1.08-074 Effect of Intrapleural Perfusion Hyperthermic Chemotherapy in Non-Small Cell Lung Cancer with Pleural Seeding
Authors: Hyo-Jun Jang, Kyung Wook Shin, Sukki Cho, Sook Whan Sung, Kwhanmien Kim, Sanghoon Jheon
Journal: Journal of Thoracic Oncology (2017)
Abstract B41: Statins show synthetic lethality in E-cadherin-deficient cells and are synergistic with SRC and HDAC inhibitors
Authors: Andrew Single, Augustine Chen, Bryony Telford, Henry Beetham, Parry Guilford
Journal: Clinical Cancer Research (2017)

Abstract E-cadherin (CDH1) is a cell-cell adhesion protein implicated in the epithelial-mesenchymal transition and frequently dysregulated in diffuse gastric cancer (DGC) and invasive lobular breast cancer (ILBC). Germline CDH1 mutations define hereditary diffuse gastric cancer (HDGC), a rare cancer syndrome characterised by highly penetrant DGC and an elevated rate of ILBC in females. There is a strong need to develop specific chemopreventative strategies for CDH1 germline mutation carriers which are capable of reducing the viability of early stage CDH1-deficient cancers whilst minimizing side effects. We have previously applied a synthetic lethal approach to an isogenic pair of MCF10A breast cell lines, one with and one without functional CDH1 expression (MCF10A CDH1-/-), to screen for drugs which preferentially reduce the viability of CDH1-deficient cells. This led to our finding that histone deacetylase inhibitors (HDACi; entinostat and vorinostat) and SRC inhibitors (SRCi; saracatinib) are involved in synthetic lethal interactions with MCF10A CDH1-/- cells. Single agent therapy, however, only produces a modest synthetic lethal effect, leading to our interest in developing synergistic drug combinations. We have now shown that statins, inhibitors of the HMG-CoA reductase enzyme, also show a synthetic lethal phenotype in the MCF10A isogenic cell line pair. This result suggests that survival of E-cadherin-deficient cells may be enhanced by the mevalonate pathway, a metabolic pathway responsible for synthesizing prenyl groups and subsequently activating the small GTPase proteins Rho, Rac, and Cdc42. SRC is also a known activator of GTPase proteins and combined statin and saracatinib treatment caused an enhanced reduction in cell viability in the isogenic MCF10A cells whilst maintaining the synthetic lethal phenotype. This drug combination was shown to be synergistic in both cell lines using the Chou-Talalay median effect analysis and is the first known example of synergy between a statin and SRC inhibitor. Combined statin and HDACi treatment also enhanced cell viability inhibition and was synthetic lethal in the MCF10A pair. This effect was observed using both class-I specific (entinostat) and pan- (vorinostat) HDACi and was synergistic in both cell lines using median effect analysis. These are the first known examples of synergistic drug combinations being used in the field of synthetic lethality and serve as a foundation for novel DGC and ILBC treatment options. Citation Format: Andrew Single, Augustine Chen, Bryony Telford, Henry Beetham, Parry Guilford. Statins show synthetic lethality in E-cadherin-deficient cells and are synergistic with SRC and HDAC inhibitors. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B41.