Welcome to Dana-Farber's Research News
March 01, 2023
This twice-monthly newsletter highlights the research endeavors at Dana-Farber Cancer Institute, noting recently published papers available from PubMed where Dana-Farber faculty are listed as first or senior authors. If you are a Dana-Farber faculty member and you think your paper is missing from Research News, please let us know at: Michael_buller@dfci.harvard.edu.
Blood
Castillo JJ, Branagan AR, Sermer D, Flynn CA, Meid K, Little M, Stockman K, White T, Canning A, Guerrera ML, Kofides A, Liu S, Liu X, Richardson K, Tsakmaklis N, Patterson CJ, Hunter ZR, Treon SP, Sarosiek S
Concurrent Bruton tyrosine kinase and BCL2 inhibition has not yet been investigated in Waldenström macroglobulinemia (WM). We performed an investigator-initiated trial of ibrutinib and venetoclax in symptomatic treatment-naïve patients with MYD88-mutated WM. Patients received ibrutinib 420 mg once daily (cycle 1), followed by a ramp-up of venetoclax to 400 mg daily (cycle 2). The combination was then administered for 22 additional 4-week cycles. The attainment of very good partial response (VGPR) was the primary end point. Forty-five patients were enrolled in this study. The median baseline characteristics were as follows: age 67 years, serum IgM 43 g/L, and hemoglobin 102 g/L. Seventeen patients (38%) carried CXCR4 mutations. Nineteen patients (42%) achieved VGPR. Grade 3 or higher adverse events included neutropenia (38%), mucositis (9%), and tumor lysis syndrome (7%). Atrial fibrillation occurred in 3 (9%), and ventricular arrhythmia in 4 (9%) patients that included 2 grade 5 events. With a median follow-up of 24.4 months, the 24-month progression-free survival (PFS) and overall survival (OS) rates were 76% and 96%, respectively, and were not impacted by CXCR4 mutations. The median time on therapy was 10.2 months, and the median time after the end of therapy (EOT) was 13.3 months. Eleven of the 12 progression events occurred after EOT, and the 12-month PFS rates after EOT were 79%; 93% if VGPR was attained, and 69% for other patients (P = .12). Ibrutinib and venetoclax induced high VGPR rates and durable responses after EOT, although they were associated with a higher-than-expected rate of ventricular arrhythmia in patients with WM, leading to early study treatment termination. This trial was registered at www.clinicaltrials.gov as #NCT04273139.
Blood
Jacobson CA
Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Approval was supported by the phase 2, multicenter, single-arm ZUMA-5 study of axi-cel for patients with R/R indolent non-Hodgkin lymphoma (iNHL; N = 104), including FL and marginal zone lymphoma (MZL). In the primary analysis (median follow-up, 17.5 months), the overall response rate (ORR) was 92% (complete response rate, 74%). Here, we report long-term outcomes from ZUMA-5. Eligible patients with R/R iNHL after ?2 lines of therapy underwent leukapheresis, followed by lymphodepleting chemotherapy and axi-cel infusion (2 × 106 CAR T cells per kg). The primary end point was ORR, assessed in this analysis by investigators in all enrolled patients (intent-to-treat). After median follow-up of 41.7 months in FL (n = 127) and 31.8 months in MZL (n = 31), ORR was comparable with that of the primary analysis (FL, 94%; MZL, 77%). Median progression-free survival was 40.2 months in FL and not reached in MZL. Medians of overall survival were not reached in either disease type. Grade ?3 adverse events of interest that occurred after the prior analyses were largely in recently treated patients. Clinical and pharmacokinetic outcomes correlated negatively with recent exposure to bendamustine and high metabolic tumor volume. After 3 years of follow-up in ZUMA-5, axi-cel demonstrated continued durable responses, with very few relapses beyond 2 years, and manageable safety in patients with R/R iNHL. The ZUMA-5 study was registered at www.clinicaltrials.gov as #NCT03105336.
Cell
Inherited Blood Cancer Predisposition Through Altered Transcription Elongation
Zhao J, Cato LD, Arora UP, Bao EL, Bryant SC, Jia Y, Goldman SR, Armstrong SA, Sankaran VG
Despite advances in defining diverse somatic mutations that cause myeloid malignancies, a significant heritable component for these cancers remains largely unexplained. Here, we perform rare variant association studies in a large population cohort to identify inherited predisposition genes for these blood cancers. CTR9, which encodes a key component of the PAF1 transcription elongation complex, is among the significant genes identified. The risk variants found in the cases cause loss of function and result in a ?10-fold increased odds of acquiring a myeloid malignancy. Partial CTR9 loss of function expands human hematopoietic stem cells (HSCs) by increased super elongation complex-mediated transcriptional activity, which thereby increases the expression of key regulators of HSC self-renewal. By following up on insights from a human genetic study examining inherited predisposition to the myeloid malignancies, we define a previously unknown antagonistic interaction between the PAF1 and super elongation complexes. These insights could enable targeted approaches for blood cancer prevention.
Gastroenterology
Aney KJ, Jeong WJ, Chen E, Wang A, Koak P, Dougan SK, Nissim S
BACKGROUND & AIMS: Acinar cells produce digestive enzymes that impede transcriptomic characterization of the exocrine pancreas. Thus, single-cell RNA-sequencing (scRNA-seq) studies of the pancreas underrepresent acinar cells relative to histological expectations, and a robust approach to capture pancreatic cell responses in disease states is needed. We sought to innovate a method that overcomes these challenges to accelerate study of the pancreas in health and disease.
METHODS: We introduce FixNCut, a scRNA-seq approach where tissue is reversibly fixed with dithiobis(succinimidyl propionate) prior to dissociation and single-cell preparation. We apply FixNCut to an established mouse model of acute pancreatitis, validate findings using GeoMx whole transcriptome atlas (WTA) profiling, and integrate our data with prior studies to benchmark our method in both mouse and human pancreas datasets.
RESULTS: FixNCut achieves unprecedented definition of challenging pancreatic cells including acinar and immune populations in homeostasis and acute pancreatitis, and identifies changes in all major cell types during injury and recovery. We define the acinar transcriptome during homeostasis and acinar-to-ductal metaplasia and establish a unique gene set to measure deviation from normal acinar identity. We characterize pancreatic immune cells, and analysis of T-cell subsets reveals a polarization of the homeostatic pancreas towards type-2 immunity. We report immune responses during acute pancreatitis and recovery, including early neutrophil infiltration, expansion of dendritic cell subsets, and a substantial shift in the transcriptome of macrophages due to both resident macrophage activation and monocyte infiltration.
CONCLUSIONS: FixNCut preserves pancreatic transcriptomes to uncover novel cell states during homeostasis and following pancreatitis, establishing a broadly applicable approach and reference atlas for study of pancreas biology and disease.
Gastroenterology
Rodriguez NJ, Furniss CS, Yurgelun MB, Ukaegbu C, Fortes I, Caruso A, Schwartz AN, Stopfer JE, Underhill-Blazey M, Uno H, Horiguchi M, Garber JE, Syngal S
BACKGROUND AND AIMS: Genetic testing uptake for cancer susceptibility in family members of cancer patients is suboptimal. Among relatives of pancreatic ductal adenocarcinoma (PDAC) patients, The GENetic Education, Risk Assessment, and TEsting (GENERATE) study evaluated two online genetic education/testing delivery models and their impact on patient-reported psychological outcomes (PRPOs).
METHODS: Eligible participants had ?1 first-degree relative with PDAC, or ?1 first-/second-degree relative with PDAC with a known pathogenic germline variant in one of thirteen PDAC predisposition genes. Participants were randomized by family, between 5/8/2019-6/1/2021. Arm 1 participants underwent a remote interactive telemedicine session and online genetic education. Arm 2 participants were offered online genetic education only. All participants were offered germline testing. The primary outcome was genetic testing uptake, compared by permutation tests and mixed-effects logistic regression models. We hypothesized that Arm 1 participants would have a higher genetic testing uptake than Arm 2. Validated surveys were administered to assess patient-reported anxiety, depression, and cancer worry at baseline and 3-months post-intervention.
RESULTS: 424 families were randomized, including 601 participants (n=296 Arm 1; n=305 Arm 2), 90% of whom completed genetic testing (Arm 1 (87%); Arm 2 (93%), p=0.014). Arm 1 participants were significantly less likely to complete genetic testing compared to Arm 2 (adjusted ratio (Arm1/Arm2) 0.90, 95% confidence interval 0.78-0.98). Among participants who completed PRPO questionnaires (Arm 1 (n=194); Arm 2 (n=206)), the intervention did not impact mean anxiety, depression or cancer worry scores.
CONCLUSIONS: Remote genetic education and testing can be a successful and complementary option for delivering genetics care.
Journal of Clinical Oncology
Crenolanib and Intensive Chemotherapy in Adults with Newly Diagnosed FLT3-Mutated AML
Stone RM
PURPOSE: Crenolanib is a second-generation tyrosine kinase inhibitor with activity against FLT3-ITD- and TKD-mutant AML. We conducted a trial of crenolanib plus intensive chemotherapy in adults with newly diagnosed FLT3-mutant AML.
METHODS: Eligible patients were 18 years and older. Induction chemotherapy consisted of cytarabine (100 mg/m2) continuous infusion on days 1-7 and anthracycline (daunorubicin 60-90 mg/m2 or idarubicin 12 mg/m2, once daily) on days 1-3 followed by consolidation with high-dose cytarabine (1-3 g/m2 twice daily on days 1, 3, 5) and/or allogeneic transplant. Crenolanib (100 mg thrice a day) was given from day 9 until 72 hours before the next cycle, after consolidation, and for 12 months after consolidation or transplant.
RESULTS: Forty-four patients (median age, 57; range, 19-75 years) were enrolled. Thirty-six had FLT3-ITD, and 11 had FLT3-TKD mutations. European LeukemiaNet 2017 disease risk was favorable in 34%, intermediate in 30%, and adverse in 36%. The overall response rate was 86% (complete remission [CR], 77%; CR with incomplete count recovery [CRi], 9%): 90% in patients 60 years and younger and 80% in older patients. Measurable residual disease-negative CR/CRi rates were 89% and 45%, respectively. With a 45-month follow-up, median overall survival has not been reached and the median event-free survival was 44.7 months. Among younger patients, the estimated 3-year survival was 71.4% with 15% cumulative incidence of relapse. Treatment-related serious adverse events included febrile neutropenia, diarrhea, and nausea. The median time to platelets ?100,000/µL and absolute neutrophil count ?1,000/µL during induction was 29 and 32 days, respectively. No new FLT3-mutant clones were detected at relapse in patients completing consolidation.
CONCLUSION: Crenolanib plus intensive chemotherapy in adults with newly diagnosed FLT3-mutant AML results in high rate of deep responses and long-term survival with acceptable toxicity. A randomized trial of crenolanib versus midostaurin plus chemotherapy in younger patients is ongoing.
Journal of Clinical Oncology
Haas-Kogan DA, Liu KX
PURPOSE: The PNOC001 phase II single-arm trial sought to estimate progression-free survival (PFS) associated with everolimus therapy for progressive/recurrent pediatric low-grade glioma (pLGG) on the basis ofphosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway activation as measured by phosphorylated-ribosomal protein S6 and to identify prognostic and predictive biomarkers.
PATIENTS AND METHODS: Patients, age 3-21 years, with progressive/recurrent pLGG received everolimus orally, 5 mg/m2 once daily. Frequency of driver gene alterations was compared among independent pLGG cohorts of newly diagnosed and progressive/recurrent patients. PFS at 6 months (primary end point) and median PFS (secondary end point) were estimated for association with everolimus therapy.
RESULTS: Between 2012 and 2019, 65 subjects with progressive/recurrent pLGG (median age, 9.6 years; range, 3.0-19.9; 46% female) were enrolled, with a median follow-up of 57.5 months. The 6-month PFS was 67.4% (95% CI, 60.0 to 80.0) and median PFS was 11.1 months (95% CI, 7.6 to 19.8). Hypertriglyceridemia was the most common grade ?3 adverse event. PI3K/AKT/mTOR pathway activation did not correlate with clinical outcomes (6-month PFS, active 68.4% v nonactive 63.3%; median PFS, active 11.2 months v nonactive 11.1 months; P = .80). Rare/novel KIAA1549::BRAF fusion breakpoints were most frequent in supratentorial midline pilocytic astrocytomas, in patients with progressive/recurrent disease, and correlated with poor clinical outcomes (median PFS, rare/novel KIAA1549::BRAF fusion breakpoints 6.1 months v common KIAA1549::BRAF fusion breakpoints 16.7 months; P < .05). Multivariate analysis confirmed their independent risk factor status for disease progression in PNOC001 and other, independent cohorts. Additionally, rare pathogenic germline variants in homologous recombination genes were identified in 6.8% of PNOC001 patients.
CONCLUSION: Everolimus is a well-tolerated therapy for progressive/recurrent pLGGs. Rare/novel KIAA1549::BRAF fusion breakpoints may define biomarkers for progressive disease and should be assessed in future clinical trials.
Journal of Clinical Oncology
ONC201 (Dordaviprone) in Recurrent H3 K27M-Mutant Diffuse Midline Glioma
Arrillaga-Romany I, Batchelor T, Wen PY
PURPOSE: Histone 3 (H3) K27M-mutant diffuse midline glioma (DMG) has a dismal prognosis with no established effective therapy beyond radiation. This integrated analysis evaluated single-agent ONC201 (dordaviprone), a first-in-class imipridone, in recurrent H3 K27M-mutant DMG.
METHODS: Fifty patients (pediatric, n = 4; adult, n = 46) with recurrent H3 K27M-mutant DMG who received oral ONC201 monotherapy in four clinical trials or one expanded access protocol were included. Eligible patients had measurable disease by Response Assessment in Neuro-Oncology (RANO) high-grade glioma (HGG) criteria and performance score (PS) ?60 and were ?90 days from radiation; pontine and spinal tumors were ineligible. The primary end point was overall response rate (ORR) by RANO-HGG criteria. Secondary end points included duration of response (DOR), time to response (TTR), corticosteroid response, PS response, and ORR by RANO low-grade glioma (LGG) criteria. Radiographic end points were assessed by dual-reader, blinded independent central review.
RESULTS: The ORR (RANO-HGG) was 20.0% (95% CI, 10.0 to 33.7). The median TTR was 8.3 months (range, 1.9-15.9); the median DOR was 11.2 months (95% CI, 3.8 to not reached). The ORR by combined RANO-HGG/LGG criteria was 30.0% (95% CI, 17.9 to 44.6). A ?50% corticosteroid dose reduction occurred in 7 of 15 evaluable patients (46.7% [95% CI, 21.3 to 73.4]); PS improvement occurred in 6 of 34 evaluable patients (20.6% [95% CI, 8.7 to 37.9]). Grade 3 treatment-related treatment-emergent adverse events (TR-TEAEs) occurred in 20.0% of patients; the most common was fatigue (n = 5; 10%); no grade 4 TR-TEAEs, deaths, or discontinuations occurred.
CONCLUSION: ONC201 monotherapy was well tolerated and exhibited durable and clinically meaningful efficacy in recurrent H3 K27M-mutant DMG.
Journal of Clinical Oncology
Understanding Adjuvant Therapy for Upper Tract Urothelial Carcinoma
Berg SA
Despite decades of research, the oncology community has faced significant challenges in establishing robust evidence for the role of perioperative chemotherapy for the treatment of urothelial cancer of the bladder. Although early adjuvant therapy trials suggested a potential benefit, limitations in sample size and premature closures because of poor patient accrual hampered their interpretation. Two randomized studies, however, demonstrated a survival benefit with neoadjuvant cisplatin-based chemotherapy followed by definitive local therapy, leading to its incorporation into clinical practice guidelines. Implementation of perioperative cisplatin-based chemotherapy has been limited by the advanced age and comorbidities often observed in patients with bladder cancer, ultimately restricting its applicability to a subset of patients.
Journal of the National Cancer Institute
Are Linchpin Oncologists Keeping the Wheels from Falling Off Cancer Care?
Manz CR, Barnett ML
Medical, radiation, and surgical oncologists, like other clinicians, are practicing in increasingly complex professional networks. Expanding sub specialization, increased use of advanced practice clinicians, and an increasingly part-time work force all contribute to a more interconnected, yet diffuse health-care system than in previous decades. This complexity can be bewildering to patients and physicians. Further complicating the matter is the tremendous variation across the country in the structure of oncology care networks. Particularly in resource-limited settings, clinicians specializing in medical, radiation, and surgical oncology may be in short supply, which could constrain timely patient access to more advanced treatment. The connections of these more isolated oncology clinicians to other clinicians, which constitute a complex and intricate network of referrals, could also be quite important for ensuring high-quality, multidisciplinary care that optimizes patient outcomes.
Journal of the National Cancer Institute
Association of N-Terminal Pro-Brain Natriuretic Peptide with Survival Among US Cancer Survivors
Cao C, Nohria A, Mayer EL, Partridge AH, Ligibel JA
BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) is a cardiac biomarker associated with the risk of heart failure and death in the general population but has not been explored in cancer survivors.
METHODS: Using a US nationally representative sample of adults ?20?years from the National Health and Nutrition Examination Survey from 1999 to 2004, this study compared NT-proBNP levels between non-cancer adults (n?=?12574) and cancer survivors (n?=?787) and examined the association of NT-proBNP with all-cause and cause-specific mortality among cancer survivors.
RESULTS: Cancer survivors had higher NT-proBNP levels than non-cancer adults (median: 125.4 [IQR, 52.4 to 286.0] vs 43.2 [IQR, 20.3-95.0]). In particular, survivors of breast, prostate, and colorectal cancers had higher NT-proBNP levels than non-cancer adults (multivariable-adjusted P<.05). 471 survivors died (cancer: 141; cardiac disease: 95) during a median follow-up of 13.4?years (9,393 person-years). Among cancer survivors, higher NT-proBNP levels were statistically associated with increased risks of all-cause (HR, 1.31 [95% CI, 1.18-1.46]) and cardiac (HR, 1.55 [95% CI, 1.21-2.00) mortality but not with death due to cancer (HR, 1.10 [95% CI, 0.92-1.32]). Higher NT-proBNP levels were associated with elevated overall mortality in survivors of prostate (HR, 1.45 [95% CI, 1.17-1.79]) and colorectal (HR, 1.78 [95% 1.12-2.85]) cancers (P-interaction?=?0.169). Non-linear dose-response relationships were observed between NT-proBNP and mortality, with statistically significant relationships emerging above 125?pg/ml.
CONCLUSIONS: Cancer survivors had higher NT-proBNP than non-cancer adults, and elevated NT-proBNP levels were associated with higher risks of all-cause and cardiac mortality in cancer survivors.
Lancet Oncology
Overmoyer B
BACKGROUND: The androgen receptor is a tumour suppressor in oestrogen receptor-positive breast cancer. The activity and safety of enobosarm, an oral selective androgen receptor modulator, was evaluated in women with oestrogen receptor (ER)-positive, HER2-negative, and androgen receptor (AR)-positive disease.
METHODS: Women who were postmenopausal (aged ?18 years) with previously treated ER-positive, HER2-negative, locally advanced or metastatic breast cancer with an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled in a randomised, open-label, multicentre, multinational, parallel design, phase 2 trial done at 35 cancer treatment centres in nine countries. Participants were stratified on the setting of immediately preceding endocrine therapy and the presence of bone-only metastasis and randomly assigned (1:1) to 9 mg or 18 mg oral enobosarm daily using an interactive web response system. The primary endpoint was clinical benefit rate at 24 weeks in those with centrally confirmed AR-positive disease (ie, the evaluable population). This trial is registered with ClinicalTrials.gov (NCT02463032).
FINDINGS: Between Sept 10, 2015, and Nov 28, 2017, 136 (79%) of 172 patients deemed eligible were randomly assigned to 9 mg (n=72) or 18 mg (n=64) oral enobosarm daily. Of these 136 patients, 102 (75%) patients formed the evaluable population (9 mg, n=50; 18 mg, n=52). The median age was 60·5 years (IQR 52·3-69·3) in the 9 mg group and 62·5 years (54·0-69·3) in the 18 mg group. The median follow-up was 7·5 months (IQR 2·9-14·1). At 24 weeks, 16 (32%, 95% CI 20-47) of 50 in the 9 mg group and 15 (29%, 17-43) of 52 in the 18 mg group had clinical benefit. Six (8%) of 75 patients who received 9 mg and ten (16%) of 61 patients who received 18 mg had grade 3 or grade 4 drug-related adverse events, most frequently increased hepatic transaminases (three [4%] of 75 in the 9 mg group and two [3%] of 61 in the 18 mg group), hypercalcaemia (two [3%] and two [3%]), and fatigue (one [1%] and two [3%]). Four deaths (one in the 9 mg group and three in the 18 mg group) were deemed unrelated to the study drug.
INTERPRETATION: Enobosarm has anti-tumour activity in patients with ER-positive, HER2-negative advanced breast cancer, showing that AR activation can result in clinical benefit, supporting further clinical investigation of selective AR activation strategies for the treatment of AR-positive, ER-positive, HER2-negative advanced breast cancer.
FUNDING: GTx.
Nature Chemical Biology
Antibody Discovery Identifies Regulatory Mechanisms of Protein Arginine Deiminase
Zhou X
Unlocking the potential of protein arginine deiminase 4 (PAD4) as a drug target for rheumatoid arthritis requires a deeper understanding of its regulation. In this study, we use unbiased antibody selections to identify functional antibodies capable of either activating or inhibiting PAD4 activity. Through cryogenic-electron microscopy, we characterized the structures of these antibodies in complex with PAD4 and revealed insights into their mechanisms of action. Rather than steric occlusion of the substrate-binding catalytic pocket, the antibodies modulate PAD4 activity through interactions with allosteric binding sites adjacent to the catalytic pocket. These binding events lead to either alteration of the active site conformation or the enzyme oligomeric state, resulting in modulation of PAD4 activity. Our study uses antibody engineering to reveal new mechanisms for enzyme regulation and highlights the potential of using PAD4 agonist and antagonist antibodies for studying PAD4-dependency in disease models and future therapeutic development.
Nature Communications
Epigenetic Regulation of CD38/CD48 by KDM6A Mediates NK Cell Response in Multiple Myeloma
Liu J, Wen K, Liu N, Liu Y, Wu G, Song TY, Kurata K, Penailillo J, Morelli E, Wang T, Gulla A, Tai YT, Munshi N, Richardson P, Carrasco R, Hideshima T, Anderson KC
Anti-CD38 monoclonal antibodies like Daratumumab (Dara) are effective in multiple myeloma (MM); however, drug resistance ultimately occurs and the mechanisms behind this are poorly understood. Here, we identify, via two in vitro genome-wide CRISPR screens probing Daratumumab resistance, KDM6A as an important regulator of sensitivity to Daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Loss of KDM6A leads to increased levels of H3K27me3 on the promoter of CD38, resulting in a marked downregulation in CD38 expression, which may cause resistance to Daratumumab-mediated ADCC. Re-introducing CD38 does not reverse Daratumumab-mediated ADCC fully, which suggests that additional KDM6A targets, including CD48 which is also downregulated upon KDM6A loss, contribute to Daratumumab-mediated ADCC. Inhibition of H3K27me3 with an EZH2 inhibitor resulted in CD38 and CD48 upregulation and restored sensitivity to Daratumumab. These findings suggest KDM6A loss as a mechanism of Daratumumab resistance and lay down the proof of principle for the therapeutic application of EZH2 inhibitors, one of which is already FDA-approved, in improving MM responsiveness to Daratumumab.
Nature Communications
Liu T, Zhu Q, Kai Y, Bingham T, Cha HJ, Mehta S, Schlaeger TM, Yuan GC, Orkin SH
Although emerging evidence indicates that alterations in proteins within nuclear compartments elicit changes in chromosomal architecture and differentiation, the underlying mechanisms are not well understood. Here we investigate the direct role of the abundant nuclear complex protein Matrin3 (Matr3) in chromatin architecture and development in the context of myogenesis. Using an acute targeted protein degradation platform (dTAG-Matr3), we reveal the dynamics of development-related chromatin reorganization. High-throughput chromosome conformation capture (Hi-C) experiments revealed substantial chromatin loop rearrangements soon after Matr3 depletion. Notably, YY1 binding was detected, accompanied by the emergence of novel YY1-mediated enhancer-promoter loops, which occurred concurrently with changes in histone modifications and chromatin-level binding patterns. Changes in chromatin occupancy by Matr3 also correlated with these alterations. Overall, our results suggest that Matr3 mediates differentiation through stabilizing chromatin accessibility and chromatin loop-domain interactions, and highlight a conserved and direct role for Matr3 in maintenance of chromosomal architecture.
Science Immunology
Jacobs N, Griffin GK
The lncRNA AMANZI exerts cis-regulatory control of IL-1?-mediated inflammation.
American Journal of Human Genetics
A Comprehensive Analysis of Clinical and Polygenic Germline Influences on Somatic Mutational Burden
Taraszka K, Groha S, Gusev A
Annals of Surgical Oncology
Kantor O, King TA, Jones A, Glass C, Leonard SJ, Ogayo ER, Mayer EL, Freedman RA, Mittendorf EA
Annals of Surgical Oncology
Hersh EH, Minami CA, Weiss A, King TA
Annals of Surgical Oncology
Minami CA, Jin G, Freedman RA, Schonberg MA, King TA, Mittendorf EA
Annual Review of Biochemistry
Signaling from RAS to RAF: The Molecules and Their Mechanisms
Jeon H, Tkacik E, Eck MJ
Annual Review of Physiology
The Role of the Microbiome in the Etiopathogenesis of Colon Cancer
El Tekle G, Andreeva N, Garrett WS
Bioinformatics
Conumee 2.0: Enhanced Copy-Number Variation Analysis from DNA Methylation Arrays for Humans and Mice
Daenekas B, Boniolo F, Stefan S, Benfatto S, Hovestadt V
Biostatistics
Uncertainty Directed Factorial Clinical Trials
Kotecha G, Trippa L
Blood Advances
Lane AA, Garcia JS, Raulston EG, Garzon JL, Galinsky I, Baxter EW, Leonard R, DeAngelo DJ, Luskin MR, Reilly CR, Stahl M, Stone RM, Vedula RS, Wadleigh MM, Winer ES, Stevenson KE, Neuberg DS, Ren S, Keating J
Blood Advances
Romee R, Koreth J
Blood Cancer Discovery
Bhola PD, Letai A
BMC Urology
Prostate Cancer Presentation and Management in the Middle East
Sayan M, Moningi S, Orio PF
Breast Cancer Research and Treatment
Mayer EL, Tayob N, Ren S, Savoie JJ, Spigel DR, Burris HA 3rd, Ryan PD, Harris LN, Winer EP, Burstein HJ
Cancer
Sorouri K, Sella T, Loucks M, Kirkner G, Snow C, Gelber SI, Peppercorn JM, Come SE, Partridge AH
Cancer
Florez N, Kiel L, Meza K, Wei Z, Mazzola E, Franco I
Cancer Research Communications
Goldberg J, Guerriero JL, Gross B, Rahman T, Jeselsohn R, Tolaney SM, Mittendorf EA
Circulation
Lin AE, Bapat AC, Xiao L, Niroula A, Ye J, Wong WJ, Agrawal M, Hergott CB, McConkey M, Flores-Bringas P, Shkolnik V, Milan D, Natarajan P, Libby P, Ellinor PT, Ebert BL
Clinical Cancer Research
Overcoming Resistance in Chronic Lymphocytic Leukemia-Maybe Less Is More?
Davids MS
Clinical Cancer Research
Ali LR, Lenehan PJ, Cardot-Ruffino V, Dias Costa A, Nowak JA, Wolpin BM, Abrams TA, Patel A, Clancy TE, Wang J, Mancias JD, Rahma OE, Dougan SK
Clinical Cancer Research
Singh H, Sahgal P, Kapner K, Gupta H, Li YY, Cherniack AD, El Alam R, Kerfoot J, Andrews E, Lee A, Nambiar C, Hannigan AM, Remland J, Brais L, Leahy ME, Rubinson DA, Schlechter BL, Meyerson M, Kuang Y, Paweletz CP, Aguirre AJ, Perez KJ, Huffman BM, Rossi H, Abrams TA, Sicinska ET, Parikh AR, Wolpin BM, Giannakis M, Ng K, Meyerhardt JA, Hornick JL, Sethi NS, Cleary JM
Current Neurology and Neuroscience Reports
Updated Response Assessment in Neuro-Oncology (RANO) for Gliomas
Youssef G, Wen PY
Current Opinion in Biotechnology
Two in One: The Emerging Concept of Bifunctional Antibodies
Rhee K, Zhou X
Current Treatment Options in Oncology
One Size Fits Some: Approaching Rare Malignancies of the Urinary Tract
Berg SA, McGregor BA
European Journal of Cancer
Tarantino P, Ajari O, Graham N, Vincuilla J, Parker T, Hughes ME, Tayob N, Garrido-Castro AC, Morganti S, King TA, Mittendorf EA, Lin NU, Tolaney SM
European Urology Oncology
Yim K, Hsu SH, Nolazco JI, Cagney D, Mak RH, D'Andrea V, Singer L, Williams C, Huynh E, Han Z, Martin N, Nguyen P, Kibel AS, Choueiri TK, Chang SL, Leeman JE
Gastric Cancer
Enzinger PC
Haematologica
Richardson PG, Anderson KC
Hematology/Oncology Clinics of North America
An Overview of Cervical Cancer Prevention and Control in Latin America and the Caribbean Countries
Contreras-Chavez P, Kiel L, Florez N
Hematology/Oncology Clinics of North America
State of Cancer Control in South America: Challenges and Advancement Strategies
Abuali I, Florez N
Immunity
The B7:CD28 Family and Friends: Unraveling Coinhibitory Interactions
Burke KP, Chaudhri A, Freeman GJ, Sharpe AH
International Journal of Radiation Oncology, Biology, Physics
King MT, Orio PF, D'Amico AV
Journal of the American Academy of Dermatology
Kim EY, Ruiz ES, Hanna GJ, Thakuria M, Silk AW
Journal of Cancer Survivorship
Cancer Survivorship Programs at the Dana-Farber Cancer Institute
Partridge AH, Morgans A, Knelson LP, Recklitis C, Nekhlyudov L, Chi SN, Kenney LB, Diller L, Vrooman LM
Journal of Cancer Survivorship
Contreras-Chavez P, Nekhlyudov L
Journal of Clinical Investigation
Li Z, Metzger Filho O, Goyette MA, Kamat A, Spring LM, Waks AG, King TA, Lester SC, Bellon JR, Polyak K
Journal of Nuclear Medicine
The Current and Future Roles of Precision Oncology in Advanced Breast Cancer
Jacene H
Journal of Palliative Medicine
Bolstering Advance Care Planning Measurement Using Natural Language Processing
Zupanc SN, Durieux BN, Lindvall C
Journal of Thoracic Oncology
Rotow JK, Jänne PA
JCO Oncology Practice
Bober SL
JCO Oncology Practice
AlJabban A, Paik H, Aster JC, Berliner N, Brouillard J, Brown JR, Burns KH, Castillo JJ, Card J, Dal Cin P, DeAngelo DJ, Dorfman DM, Ebert BL, Garcia JS, Jacobson CA, Lakhani H, Laubach JP, Ligon AH, Lindsley RC, Lovitch SB, Luskin MR, Morgan EA, Petrides A, Pinkus GS, Pozdnyakova O, Stone RM, Winer ES, Kim AS
JCO Oncology Practice
When Cancer Centers Snooze, Patients Lose: It is Time to Make Insomnia a Priority for Survivors
Zhou ES, Recklitis CJ, Partridge AH
Medical Physics
MV-based Relative Electron Density Estimation (iMREDe) for MR-LINAC Dose Calculation
Myronakis M, Hu YH, Jacobson MW, Williams CL, Berbeco RI
Molecular Therapy
Das S, Montepeloso A, Patel J, Cavalca E, Ferro F
Nanoscale
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