tbuckley/cabot-search huggingface dataset:
A phase 1b/2, open-label study of tivozanib in combination with durvalumab in subjects with advanced hepatocellular carcinoma (Deductive).
Authors: Farshid Dayyani, Arielle Shebay Lee, Daneng Li, Julie Haewon Rowe, Muhammad Shaalan Beg, Vijay Kasturi, Renuka V. Iyer
Journal: Journal of Clinical Oncology (2022)

TPS499 Background: Tivozanib (T, a potent and selective VEGFR 1, 2 &amp; 3 TKI) and durvalumab (D, a PD-L1 antibody) have both demonstrated single agent activity in HCC and have been combined safely with other therapies. T blocks all three VEGF receptors, and when combined with a PD-L1 inhibitor may improve patient outcomes. The combination of atezolizumab and bevacizumab (which blocks VEGF-A ligand binding to VEGFR2) has improved the standard of care in advanced hepatocellular cancer with a median PFS of 6.8 months and 1-year overall survival of 67.2%. All the currently used agents in the second-line setting, have been evaluated in pts with HCC only after exposure to sorafenib. Treatment option for the patients with HCC that progress on atezolizumab and bevacizumab, are therefore limited. Methods: Deductive (NCT03970616) is a phase 2, multicenter, open-label study to assess the safety and efficacy of tivozanib in combination with durvalumab in patients with advanced HCC. Cohort A (n=20) includes patients with untreated advanced HCC. Cohort B (n=20) includes patients with advanced HCC who have progressed on/after treatment with prior bevacizumab and atezolizumab. Eligibility criteria include age &gt;18 years, histologically or cytologically confirmed HCC, measurable or evaluable disease, Child-Pugh Class A, and ECOG PS of 0 or 1. Subjects will receive tivozanib 0.89 mg orally once daily for 21 consecutive days followed by 7 days off, and durvalumab 1500 mg intravenously every 4 weeks, and will be treated until progression or unacceptable toxicity. Study assessments include CT scan or MRI of the chest, abdomen, and pelvis every 8 weeks following Cycle 1 Day 1 until the end of treatment, and every 12 weeks during the first year and every 6 months thereafter until disease progression or start of another anti-cancer therapy. The primary objective is to establish the safety and tolerability of tivozanib in combination with durvalumab in subjects who are untreated (cohort A) or have been pre-treated with both bevacizumab and atezolizumab (cohort B). Secondary endpoints include estimation of objective response rate (ORR), median PFS and OS. Exploratory endpoints are to assess the durvalumab pharmacokinetics in the presence of tivozanib. Deductive is currently enrolling at 12 sites in the United States. Clinical trial information: NCT03970616.
TO EXAMINE A BOARD AS TO ITS SANITY.
Journal: JAMA (1905)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Prevalence of left ventricular systolic and diastolic dysfunction in Olmsted county, MN: A population-based, cross-sectional doppler-echocardiographic survey Margaret M. Redfield, John C. Burnett, Jr., Steven J. Jacobsen, Douglas W. Mahoney, Richard J. Rodeheffer. Mayo Clinic and Foundation, Rochester, MN
Journal: Journal of the American College of Cardiology (2001)
Naive T-Cell Depletion to Prevent Chronic Graft-Versus-Host Disease
Authors: Marie Bleakley, Alison Sehgal, Stuart Seropian, Melinda A. Biernacki, Elizabeth F. Krakow, Ann Dahlberg, Heather Persinger, Barbara Hilzinger, Paul J. Martin, Paul A. Carpenter, Mary E. Flowers, Jenna Voutsinas, Theodore A. Gooley, Keith Loeb, Brent L. Wood, Shelly Heimfeld, Stanley R. Riddell, Warren D. Shlomchik
Journal: Journal of Clinical Oncology (2022)

PURPOSE Graft-versus-host disease (GVHD) causes morbidity and mortality following allogeneic hematopoietic cell transplantation. Naive T cells (T N ) cause severe GVHD in murine models. We evaluated chronic GVHD (cGVHD) and other outcomes in three phase II clinical trials of T N -depletion of peripheral blood stem-cell (PBSC) grafts. METHODS One hundred thirty-eight patients with acute leukemia received T N -depleted PBSC from HLA-matched related or unrelated donors following conditioning with high- or intermediate-dose total-body irradiation and chemotherapy. GVHD prophylaxis was with tacrolimus, with or without methotrexate or mycophenolate mofetil. Subjects received CD34-selected PBSC and a defined dose of memory T cells depleted of T N . Median follow-up was 4 years. The primary outcome of the analysis of cumulative data from the three trials was cGVHD. RESULTS cGVHD was very infrequent and mild (3-year cumulative incidence total, 7% [95% CI, 2 to 11]; moderate, 1% [95% CI, 0 to 2]; severe, 0%). Grade III and IV acute GVHD (aGVHD) occurred in 4% (95% CI, 1 to 8) and 0%, respectively. The cumulative incidence of grade II aGVHD, which was mostly stage 1 upper gastrointestinal GVHD, was 71% (95% CI, 64 to 79). Recipients of matched related donor and matched unrelated donor grafts had similar rates of grade III aGVHD (5% [95% CI, 0 to 9] and 4% [95% CI, 0 to 9]) and cGVHD (7% [95% CI, 2 to 13] and 6% [95% CI, 0 to 12]). Overall survival, cGVHD-free, relapse-free survival, relapse, and nonrelapse mortality were, respectively, 77% (95% CI, 71 to 85), 68% (95% CI, 61 to 76), 23% (95% CI, 16 to 30), and 8% (95% CI, 3 to 13) at 3 years. CONCLUSION Depletion of T N from PBSC allografts results in very low incidences of severe acute and any cGVHD, without apparent excess risks of relapse or nonrelapse mortality, distinguishing this novel graft engineering strategy from other hematopoietic cell transplantation approaches.
白癜风患者管理指南
Journal: British Journal of Dermatology (2022)

Abstract Linked Article: Eleftheriadou et al. Br J Dermatol 2022; 186:18–29. 白癜风是一种常见的长期皮肤疾病。世界上约有 1% 的人口受此疾病的影响, 不论年龄、性别或种族。白癜风的类型及其稳定性有助于表明病情改善的几率 (或复发的几率) 。 在白癜风患者中, 体内产生的黑色素不足, 导致皮肤出现苍白、白色或浅粉色斑块。有时, 这些斑块会合并形成较大的区域。在极少数情况下, 超过 80% 的体表会受到影响。然而, 白癜风最常见于面部、颈部、手部、身体开口处 (鼻孔、口腔、生殖器、肚脐和眼周) 和皮肤皱褶处 (腋下和腹股沟区域) 。 英国皮肤科医生协会 (BAD) 组建了一个专家组, 由皮肤科医生、临床心理学家、患者代表和技术团队组成。他们审查了截至 2019 年 5 月发表的相关文章, 以便使用严格的 GRADE 系统 (建议评估、开发和评估等级) 生成基于证据的建议, 以便制定指南。 该指南有 28 个管理建议、9 个未来研究建议和 5 个建议稽查点 (医疗专业人员使用稽查点, 以系统的方式评估、评价和改善患者接受的护理质量) 。管理方法以流程图的形式提供, 临床医生可以一目了然地查看治疗白癜风患者时建议的关键行动。 根据该群体的经历, 白癜风患者可能会感受到高度的社交焦虑、耻辱感和歧视。他们建议, 除了推荐治疗外, 还应对患者生活质量、精神和社会健康进行常规评估。白癜风患者也应获得有关自助的信息, 并在适当情况下转诊接受心理治疗。 该指南用于更新白癜风的 BAD 患者信息单 (PIL), 可通过 BAD 网站访问 (www.skinhealthinfo.org.uk/a-z-conditions-treatments/)。 Linked Article: Eleftheriadou et al. Br J Dermatol 2022; 186:18–29.
Review of US medical school finances, 1993-1994
Authors: J. L. Ganem
Journal: JAMA (1995)

THIS ANNUAL financial review of the 126 US medical schools accredited by the Liaison Committee on Medical Education (LCME) reports revenues and expenditures for fiscal year 1993-1994 and identifies patterns in the financing of medical education during the past 3 years. To display recent patterns in medical school financing amid the current economic climate, we chose 1991-1992 as the base year. The review also highlights changes in student financial aid during a 3-year period and differences in the funding of public and private medical schools for fiscal year 1993-1994. <h3>DATA SOURCES AND CHARACTERISTICS</h3> For the 1993-1994 fiscal year, all 126 LCME-accredited US medical schools responded to the LCME's Part I-A annual financial questionnaire (AFQ). For the same fiscal year, 125 accredited US medical schools reported their financial aid information on the LCME Part I-B student financial aid questionnaire. This analysis used data derived from the results of these questionnaires. Where
Morphological Constitution and Smoking
Authors: Carl C. Selzer
Journal: JAMA (1965)

<h3>To the Editor:—</h3> Unfortunately the article by Livson and Stewart (<b>192</b>: 806 [June 7] 1965) on the question of morphological constitution and smoking has failed to make a valid contribution to the subject. It neither provides "further" sound data nor a constructive "evaluation" of the problem. The authors, having pooled the data of two separate populations, compared cigarette smokers and nonsmokers with respect to five anthropometric measures and found "no statistically significant morphological difference between these groups." Naively, they treated their basic data as if they were dealing with a single morphologically homogeneous population from which they could properly draw smoking cohorts. But this is palpably not true. If they had taken the necessary initial precaution of examining the original populations prior to pooling, they would have found (as this writer has determined) the two parent series (Oakland and Guidance) to be morphologically different. Thus, only if the percentages of
Abstract 348: Impact of Low and High Partial Pressure of Carbon Dioxide on Neuron Specific Enolase Derived from Serum and Cerebrospinal Fluid in Patients Who Underwent Targeted Temperature Management After Out-of-hospital Cardiac Arrest: A Retrospective Study
Authors: Changshin Kang
Journal: Circulation (2020)

Aim: In a previous study, low and high-normal arterial carbon dioxide tension (PaCO 2 ) were not associated with serum neuron specific enolase (NSE) in cardiac arrest survivors. We assessed the effect of PaCO 2 on NSE in cerebrospinal fluid (CSF) and serum. Methods: This was a retrospective study. PaCO 2 for the first 24 h was analysed in four means, qualitative exposure state (qES), time-weighted average (TWA), median, and minimum-maximum (Min-Max). These subgroups were divided into low (LCO 2 ) and high PaCO 2 (HCO 2 ) groups defined as PaCO 2 ≤35.3 and PaCO 2 &gt;43.5 mmHg, respectively. NSE was measured at 24, 48, and 72 h (sNSE 24,48,72 and cNSE 24,48,72 ) from return of spontaneous circulation (ROSC). The primary outcome was the association between PaCO 2 and the NSE measured at 24 h after ROSC. Results: Forty-two subjects (male, 33; 78.6%) were included in total cohort. PaCO 2 in TWA subgroup was associated with cNSE 24,48,72 , while PaCO 2 in the other subgroup were only associated with cNSE 24 . PaCO 2 and cNSE in qES subgroup showed good correlation (r= -0.61; p&lt; 0.01), and in TWA, Median, and Min-Max subgroup showed moderate correlations (r= -0.57, r= -0.48, and r= -0.60; p&lt; 0.01). Contrastively, sNSE was not associated and correlated with PaCO 2 in all analysis. Poor neurological outcome in LCO 2 was significantly higher than HCO 2 in qES, TWA, and Median subgroups ( p&lt; 0.01, p&lt; 0.01, and p= 0.02). Conclusion: Association was found between NSE and PaCO 2 using CSF, despite including normocapnic ranges; TWA of PaCO 2 may be most strongly associated with CSF NSE levels. A prospective, multi-centre study is required to confirm our results.
Recent development on COX-2 inhibitors as promising anti-inflammatory agents: The past 10 years
Authors: Zhiran Ju, Menglan Li, Junde Xu, Daniel C. Howell, Zhiyun Li, Fen-Er Chen
Journal: Acta Pharmaceutica Sinica B (2022)

Cyclooxygenases play a vital role in inflammation and are responsible for the production of prostaglandins. Two cyclooxygenases are described, the constitutive cyclooxygenase-1 and the inducible cyclooxygenase-2, for which the target inhibitors are the non-steroidal anti-inflammatory drugs (NSAIDs). Prostaglandins are a class of lipid compounds that mediate acute and chronic inflammation. NSAIDs are the most frequent choices for treatment of inflammation. Nevertheless, currently used anti-inflammatory drugs have become associated with a variety of adverse effects which lead to diminished output even market withdrawal. Recently, more studies have been carried out on searching novel selective COX-2 inhibitors with safety profiles. In this review, we highlight the various structural classes of organic and natural scaffolds with efficient COX-2 inhibitory activity reported during 2011–2021. It will be valuable for pharmaceutical scientists to read up on the current chemicals to pave the way for subsequent research.
TCT-443 Predictors of Reocclusion After Successful Drug-Eluting Stent Supported Percutaneus Coronary Intervention for Chronic Total Occlusion
Authors: Renato Valenti, Ruben Vergara, Angela Migliorini, Nazario Carrabba, Guido Parodi, Giampaolo Cerisano, Piergiovanni Buonamici, David Antoniucci
Journal: Journal of the American College of Cardiology (2012)
Capecitabine plus irinotecan versus 5-FU/FA/irinotecan +/− celecoxib in first line treatment of metastatic colorectal cancer. Safety results of the prospective multicenter EORTC phase III study 40015
Authors: C.-H. Kohne, J. de Greve, C. Bokemeyer, I. Lang, P. Vergauwe, D. Braumann, M. Debois, B. Meulemans, P. Therasse, E. van Cutsem
Journal: Journal of Clinical Oncology (2005)

3525 Background: Oral fluoropyrimidines in combination with irinotecan may be an alternative to infusional 5-FU/FA plus irinotecan. Also, Cox-2 inhibitors may enhance the antineoplastic activity of chemotherapy (CT). Methods: In a 2x2 factorial design patients with ECOG PS < 2, age > 18 and measurable metastatic colorectal cancer were randomised to receive FOLFIRI (Douillard’s regimen Lancet 2000) or capecitabine 2x1g/m2 d1–14 plus irinotecan 250mg/m2 d1, qd22 (CAPE/IRI). Pts. were also randomised to receive celecoxib 2x400mg or placebo. It was planned to randomise 692 patients to compare PFS as primary endpoint. Supported by Roche - Pfizer. Results: 85 patients were randomised between May 2003 and April 2004 (44 to CAPE/IRI and 41 to FOLFIRI), at which time the trial was suspended due to occurrence of 8 fatal events not due to progression of disease. On site visits were performed and the data collected on patients who died were analysed by a panel of experts. Six deaths (5 treatment related) occurred in the CAPE/IRI arm and 2 deaths (both treatment related) in the FOLFIRI arm. 2 of the deceased patients in each CT arm had received celecoxib. Infectious complications (pneumonia and neutropenic sepsis) were the cause of death in the 2 FOLFIRI patients. 3 pts in the CAPE/IRI arm died of a thrombembolic event (2 treatment related) and 3 of severe diarrhea (all treatment related). 2 of these latter 3 patients had in addition a thrombembolic event (mainly pulmonary embolism). Baseline characteristics were similar in both arms. Among the patients who were documented to have started the CT, 61% required a dose reduction in the CAPE/IRI arm (n=18) (45% due to non haematological toxicity), and only 7% in the FOLFIRI arm (n=15). Grade ≥3 diarrhea occurred in 39% and 7% of the patients receiving CAPE/IRI and FOLFIRI, respectively. Conclusions: CAPE/IRI in this dose and schedule is considered as not feasible. Celecoxib has probably not contributed to the deaths. The EORTC GI group plans to start a randomised phase 2 study with 20% dose reduction of Cape/Iri plus bevacizumab vs. FOLFIRI (Tournigand et al. JCO 2004) plus bevacizumab. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer, Roche
X-RAYS DURING PREGNANCY
Journal: JAMA (1953)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Covid-19: WHO recommends baricitinib and sotrovimab to treat patients
Authors: Zosia Kmietowicz
Journal: BMJ (2022)

Covid-19: WHO recommends baricitinib and sotrovimab to treat patients Zosia KmietowiczThe Janus kinase (JAK) inhibitor baricitinib, which is also used to treat rheumatoid arthritis, is strongly recommended for patients with severe or critical covid-19 in combination with corticosteroids, an expert group from the World Health Organization has written in The BMJ.
A Treatise on Obstetric Labor
Journal: JAMA (1949)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Appendicoliths, Antibiotic Treatment Failure, and Appendectomy—Is the Glass Half Full or Half Empty?
Authors: Liane S. Feldman, Lawrence Lee
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Current Medical Literature
Journal: JAMA (1926)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Systems medicine dissection of chr1q-amp reveals a novel PBX1-FOXM1 axis for targeted therapy in multiple myeloma
Authors: Nikolaos Trasanidis, Alexia Katsarou, Kanagaraju Ponnusamy, Yao-An Shen, Ioannis V. Kostopoulos, Bien Bergonia, Keren Keren, Paudel Reema, Xiaolin Xiao, Richard M. Szydlo, Pierangela M. R. Sabbattini, Irene A. G. Roberts, Holger W. Auner, Kikkeri N. Naresh, Aristeidis Chaidos, Tian-Li Wang, Luca Magnani, Valentina S. Caputo, Anastasios Karadimitris
Journal: Blood (2022)

Understanding the biological and clinical impact of copy number aberrations (CNAs) on the development of precision therapies in cancer remains an unmet challenge. Genetic amplification of chromosome 1q (chr1q-amp) is a major CNA conferring an adverse prognosis in several types of cancer, including in the blood cancer multiple myeloma (MM). Although several genes across chromosome 1 (chr1q) portend high-risk MM disease, the underpinning molecular etiology remains elusive. Here, with reference to the 3-dimensional (3D) chromatin structure, we integrate multi-omics data sets from patients with MM with genetic variables to obtain an associated clinical risk map across chr1q and to identify 103 adverse prognosis genes in chr1q-amp MM. Prominent among these genes, the transcription factor PBX1 is ectopically expressed by genetic amplification and epigenetic activation of its own preserved 3D regulatory domain. By binding to reprogrammed superenhancers, PBX1 directly regulates critical oncogenic pathways and a FOXM1-dependent transcriptional program. Together, PBX1 and FOXM1 activate a proliferative gene signature that predicts adverse prognosis across multiple types of cancer. Notably, pharmacological disruption of the PBX1-FOXM1 axis with existing agents (thiostrepton) and a novel PBX1 small molecule inhibitor (T417) is selectively toxic against chr1q-amp myeloma and solid tumor cells. Overall, our systems medicine approach successfully identifies CNA-driven oncogenic circuitries, links them to clinical phenotypes, and proposes novel CNA-targeted therapy strategies in MM and other types of cancer.