Welcome to Dana-Farber's Research News
February 15, 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
Morelli E, Fulciniti M, Samur MK, Wert-Lamas L, Gulla A, Aktas-Samur A, Talluri S, Bianchi G, Johnstone M, Liu N, Gramegna D, Maisano D, Tai YT, Chauhan D, Hideshima T, Shammas MA, Anderson KC, Novina CD, Munshi NC
Long noncoding RNAs (lncRNAs) can drive tumorigenesis and are susceptible to therapeutic intervention. Here, we used a large-scale CRISPR interference viability screen to interrogate cell-growth dependency to lncRNA genes in multiple myeloma (MM) and identified a prominent role for the miR-17-92 cluster host gene (MIR17HG). We show that an MIR17HG-derived lncRNA, named lnc-17-92, is the main mediator of cell-growth dependency acting in a microRNA- and DROSHA-independent manner. Lnc-17-92 provides a chromatin scaffold for the functional interaction between c-MYC and WDR82, thus promoting the expression of ACACA, which encodes the rate-limiting enzyme of de novo lipogenesis acetyl-coA carboxylase 1. Targeting MIR17HG pre-RNA with clinically applicable antisense molecules disrupts the transcriptional and functional activities of lnc-17-92, causing potent antitumor effects both in-vitro and in-vivo in 3 preclinical animal models, including a clinically relevant patient-derived xenograft NSG mouse model. This study establishes a novel oncogenic function of MIR17HG and provides potent inhibitors for translation to clinical trials.
Blood
Penter L, Liu Y, Wolff JO, Yang L, Taing L, Jhaveri A, Southard J, Cullen N, Pfaff KL, Cieri N,
Oliveira G, Ranasinghe S, Leonard R, Robertson T, Morgan EA, Li S, Rodig SJ, Cibulskis C,
Gabriel S, Ritz J, Neuberg D, Hodi FS, Davids MS, Livak KJ, Altreuter J, Michor F, Soiffer RJ,
Garcia JS, Wu CJ
The challenge of eradicating leukemia for patients with acute myelogenous leukemia (AML) following initial cytoreduction has motivated modern efforts to combine synergistic active modalities including immunotherapy. Recently, the ETCTN/CTEP 10026 (NCT02890329) study tested the combination of the DNA methyltransferase inhibitor decitabine together with the immune checkpoint inhibitor ipilimumab for AML/myelodysplastic syndrome (MDS) either following allogeneic hematopoietic stem cell transplantation (HSCT) or in the HSCT-naive setting. Integrative transcriptome-based analysis of 304,961 individual marrow-infiltrating cells for 18 of 48 subjects treated on study revealed the strong association of response with a high baseline ratio of T to AML cells. Clinical responses were predominantly driven by decitabine-induced cytoreduction. Evidence of immune activation was only apparent following ipilimumab exposure, which altered CD4+ T cell gene expression, in line with ongoing T cell differentiation and increased frequency of marrow-infiltrating regulatory T cells. For post-HSCT samples, relapse could be attributed to insufficient clearing of malignant clones in progenitor cell populations. In contrast to AML/MDS bone marrow, the transcriptomes of leukemia cutis samples from patients with durable remission after ipilimumab monotherapy showed evidence of increased infiltration with antigen-experienced resident memory T cells and higher expression of CTLA-4 and FOXP3. Altogether, activity of combined decitabine and ipilimumab is impacted by cellular expression states within the microenvironmental niche of leukemia cells. The inadequate elimination of leukemic progenitors mandates urgent development of novel approaches for targeting these cell populations to generate long-lasting responses.
Blood
The End of the Beginning: Application of Single-Cell Sequencing to Chronic Lymphocytic Leukemia
Nagler A, Wu CJ
Single-cell analysis has emerged over the past decade as a transformative technology informative for the systematic analysis of complex cell populations such as in cancers and the tumor immune microenvironment. The methodologic and analytical advancements in this realm have evolved rapidly, scaling from but a few cells at its outset to the current capabilities of processing and analyzing hundreds of thousands of individual cells at a time. The types of profiling attainable at individual cell resolution now range from genetic and transcriptomic characterization and extend to epigenomic and spatial analysis. Additionally, the increasing ability to achieve multiomic integration of these data layers now yields ever richer insights into diverse molecular disease subtypes and the patterns of cellular circuitry on a per-cancer basis. Over the years, chronic lymphocytic leukemia (CLL) consistently has been at the forefront of genomic investigation, given the ready accessibility of pure leukemia cells and immune cells from circulating blood of patients with this disease. Herein, we review the recent forays into the application of single-cell analysis to CLL, which are already revealing a new understanding of the natural progression of CLL, the impact of novel therapies, and the interactions with coevolving nonmalignant immune cell populations. As we emerge from the end of the beginning of this technologic revolution, CLL stands poised to reap the benefits of single-cell analysis from the standpoints of uncovering fresh fundamental biological knowledge and of providing a path to devising regimens of personalized diagnosis, treatment, and monitoring.
Journal of Clinical Oncology
Konstantinopoulos PA, Lee EK, Xiong N, Krasner C, Campos S, Kolin DL, Liu JF, Horowitz N,
Wright AA, Bouberhan S, Penson RT, Yeku O, Bowes B, Needham H, Hayes M, Sawyer H, Polak M, Shea M, Cheng SC, Castro C, Matulonis UA
PURPOSE: Estrogen receptor (ER)-positive endometrial cancers (ECs) are characterized by phosphatidylinositol 3-kinase (PI3K) and receptor tyrosine kinase (RTK)/RAS/b-catenin (CTNNB1) pathway alterations in approximately 90% and 80% of cases, respectively. Extensive cross-talk between ER, PI3K, and RTK/RAS/CTNNB1 pathways leads to both ligand-dependent and ligand-independent ER transcriptional activity as well as upregulation of cyclin D1 which, in complex with cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), is a critical regulator of cell cycle progression and a key mediator of resistance to hormonal therapy. We hypothesized that the combination of the aromatase inhibitor letrozole and CDK4/6 inhibitor abemaciclib would demonstrate promising activity in this setting.
METHODS: We conducted a phase II, two-stage study of letrozole/abemaciclib in recurrent ER-positive EC. Eligibility criteria included measurable disease, no limit on prior therapies, and all EC histologies; prior hormonal therapy was allowed. Primary end points were objective response rate by RECIST 1.1 and progression-free survival (PFS) rate at 6 months.
RESULTS: At the data cutoff date (December 03, 2021), 30 patients (28 with endometrioid EC) initiated protocol therapy; 15 (50%) patients had prior hormonal therapy. There were nine total responses (eight confirmed), for an objective response rate of 30% (95% CI, 14.7 to 49.4), all in endometrioid adenocarcinomas. Median PFS was 9.1 months, PFS at 6 months was 55.6% (95% CI, 35.1 to 72), and median duration of response was 7.4 months. Most common grade 3 treatment-related adverse events were neutropenia (20%) and anemia (17%). Responses were observed regardless of grade, prior hormonal therapy, mismatch repair, and progesterone receptor status. Exploratory tumor profiling revealed several mechanistically relevant candidate predictors of response (CTNNB1, KRAS, and CDKN2A mutations) or absence of response (TP53 mutations), which require independent validation.
CONCLUSION: Letrozole/abemaciclib demonstrated encouraging and durable evidence of activity in recurrent ER positive endometrioid EC.
Journal of Clinical Oncology
Matulonis UA
Matulonis UA
PURPOSE: Single-agent chemotherapies have limited activity and considerable toxicity in patients with platinum-resistant epithelial ovarian cancer (PROC). Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate targeting folate receptor a (FRa). SORAYA is a single-arm, phase II study evaluating efficacy and safety of MIRV in patients with PROC.
METHODS: SORAYA enrolled FRa-high patients with PROC who had received one to three prior therapies, including required bevacizumab. The primary end point was confirmed objective response rate (ORR) by investigator; duration of response was the key secondary end point.
RESULTS: One hundred six patients were enrolled; 105 were evaluable for efficacy. All patients had received prior bevacizumab, 51% had three prior lines of therapy, and 48% received a prior poly ADP-ribose polymerase inhibitor. Median follow-up was 13.4 months. ORR was 32.4% (95% CI, 23.6 to 42.2), including five complete and 29 partial responses. The median duration of response was 6.9 months (95% CI, 5.6 to 9.7). In patients with one to two priors, the ORR by investigator was 35.3% (95% CI, 22.4 to 49.9) and in patients with three priors was 30.2% (95% CI, 18.3 to 44.3). The ORR by investigator was 38.0% (95% CI, 24.7 to 52.8) in patients with prior poly ADP-ribose polymerase inhibitor exposure and 27.5% (95% CI, 15.9 to 41.7) in those without. The most common treatment-related adverse events (all grade and grade 3-4) were blurred vision (41% and 6%), keratopathy (29% and 9%), and nausea (29% and 0%). Treatment-related adverse events led to dose delays, reductions, and discontinuations in 33%, 20%, and 9% of patients, respectively.
CONCLUSION: MIRV demonstrated consistent clinically meaningful antitumor activity and favorable tolerability and safety in patients with FRa-high PROC who had received up to three prior therapies, including bevacizumab, representing an important advance for this biomarker-selected population.
Journal of Clinical Oncology
Weil BR, Weldon CB, Mullen EA, Madenci AL
PURPOSE: To evaluate long-term morbidity and mortality among unilateral, nonsyndromic Wilms tumor (WT) survivors according to conventional treatment regimens.
METHODS: Cumulative incidence of late mortality (5 years from diagnosis) and chronic health conditions (CHCs) were evaluated in WT survivors from the Childhood Cancer Survivor Study. Outcomes were evaluated by treatment, including nephrectomy combined with vincristine and actinomycin D (VA), VA + doxorubicin + abdominal radiotherapy (VAD + ART), VAD + ART + whole lung radiotherapy, or receipt of 4 chemotherapy agents.
RESULTS: Among 2,008 unilateral WT survivors, 142 deaths occurred (standardized mortality ratio, 2.9, 95% CI, 2.5 to 3.5; 35-year cumulative incidence of death, 7.8%, 95% CI, 6.3 to 9.2). The 35-year cumulative incidence of any grade 3-5 CHC was 34.1% (95% CI, 30.7 to 37.5; rate ratio [RR] compared with siblings 3.0, 95% CI, 2.6 to 3.5). Survivors treated with VA alone had comparable risk for all-cause late mortality relative to the general population (standardized mortality ratio, 1.0; 95% CI, 0.5 to 1.7) and modestly increased risk for grade 3-5 CHCs compared with siblings (RR, 1.5; 95% CI, 1.1 to 2.0), but remained at increased risk for intestinal obstruction (RR, 9.4; 95% CI, 3.9 to 22.2) and kidney failure (RR, 11.9; 95% CI, 4.2 to 33.6). Magnitudes of risk for grade 3-5 CHCs, including intestinal obstruction, kidney failure, premature ovarian insufficiency, and heart failure, increased by treatment group intensity.
CONCLUSION: With approximately 40% of patients with newly diagnosed WT currently treated with VA alone, the burden of late mortality/morbidity in future decades is projected to be lower than that for survivors from earlier eras. Nevertheless, the risk of late effects such as intestinal obstruction and kidney failure was elevated across all treatment groups, and there was a dose-dependent increase in risk for all grade 3-5 CHCs by treatment group intensity.
Journal of Experimental Medicine
PD-1 Blockade and CDK4/6 Inhibition Augment Nonoverlapping Features of T Cell Activation in Cancer
Ali LR, Garrido-Castro AC, Lenehan PJ, Bollenrucher N, Stump CT, Dougan M, Shapiro GI,
Tolaney SM, Dougan SK
We performed single-cell RNA-sequencing and T cell receptor clonotype tracking of breast and ovarian cancer patients treated with the CDK4/6 inhibitor ribociclib and PD-1 blockade. We highlight evidence of two orthogonal treatment-associated phenomena: expansion of T cell effector populations and promotion of T cell memory formation. Augmentation of the antitumor memory pool by ribociclib boosts the efficacy of subsequent PD-1 blockade in mouse models of melanoma and breast cancer, pointing toward sequential therapy as a potentially safe and synergistic strategy in patients.
JAMA Oncology
Association of Inflammatory Biomarkers with Survival Among Patients with Stage III Colon Cancer
Ma C, Ng K, Meyerhardt JA
IMPORTANCE: The association of chronic inflammation with colorectal cancer recurrence and death is not well understood, and data from large well-designed prospective cohorts are limited.
OBJECTIVE: To assess the associations of inflammatory biomarkers with survival among patients with stage III colon cancer.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study was derived from a National Cancer Institute-sponsored adjuvant chemotherapy trial Cancer and Leukemia Group B/Southwest Oncology Group 80702 (CALGB/SWOG 80702) conducted between June 22, 2010, and November 20, 2015, with follow-up ending on August 10, 2020. A total of 1494 patients with plasma samples available for inflammatory biomarker assays were included. Data were analyzed from July 29, 2021, to February 27, 2022.
EXPOSURES: Plasma inflammatory biomarkers (interleukin 6 [IL-6], soluble tumor necrosis factor a receptor 2 [sTNF-aR2], and high-sensitivity C-reactive protein [hsCRP]; quintiles) that were assayed 3 to 8 weeks after surgery but before chemotherapy randomization.
MAIN OUTCOMES AND MEASURES: The primary outcome was disease-free survival, defined as time from randomization to colon cancer recurrence or death from any cause. Secondary outcomes were recurrence-free survival and overall survival. Hazard ratios for the associations of inflammatory biomarkers and survival were estimated via Cox proportional hazards regression.
RESULTS: Of 1494 patients (median follow-up, 5.9 years [IQR, 4.7-6.1 years]), the median age was 61.3 years (IQR, 54.0-68.8 years), 828 (55.4%) were male, and 327 recurrences, 244 deaths, and 387 events for disease-free survival were observed. Plasma samples were collected at a median of 6.9 weeks (IQR, 5.6-8.1 weeks) after surgery. The median plasma concentration was 3.8 pg/mL (IQR, 2.3-6.2 pg/mL) for IL-6, 2.9‚103 pg/mL (IQR, 2.3-3.6‚ 103 pg/mL) for sTNF-aR2, and 2.6 mg/L (IQR, 1.2-5.6 mg/L) for hsCRP. Compared with patients in the lowest quintile of inflammation, patients in the highest quintile of inflammation had a significantly increased risk of recurrence or death (adjusted hazard ratios for IL-6: 1.52 [95% CI, 1.07-2.14]; P = .01 for trend; for sTNF-aR2: 1.77 [95% CI, 1.23-2.55]; P < .001 for trend; and for hsCRP: 1.65 [95% CI, 1.17-2.34]; P = .006 for trend). Additionally, a significant interaction was not observed between inflammatory biomarkers and celecoxib intervention for disease-free survival. Similar results were observed for recurrence-free survival and overall survival.
CONCLUSIONS AND RELEVANCE: This cohort study found that higher inflammation after diagnosis was significantly associated with worse survival outcomes among patients with stage III colon cancer. This finding warrants further investigation to evaluate whether anti-inflammatory interventions may improve colon cancer outcomes.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01150045.
Nature Cell Biology
Lu DY, Ellegast JM, Ross KN, Malone CF, Lin S, Mabe NW, Dharia NV, Meyer A, Conway A, Su AH, Seong BKA, Adane B, Gray NS, Rivera MN, Stegmaier K
Transcription factors (TFs) are frequently mutated in cancer. Paediatric cancers exhibit few mutations genome-wide but frequently harbour sentinel mutations that affect TFs, which provides a context to precisely study the transcriptional circuits that support mutant TF-driven oncogenesis. A broadly relevant mechanism that has garnered intense focus involves the ability of mutant TFs to hijack wild-type lineage-specific TFs in self-reinforcing transcriptional circuits. However, it is not known whether this specific type of circuitry is equally crucial in all mutant TF-driven cancers. Here we describe an alternative yet central transcriptional mechanism that promotes Ewing sarcoma, wherein constraint, rather than reinforcement, of the activity of the fusion TF EWS-FLI supports cancer growth. We discover that ETV6 is a crucial TF dependency that is specific to this disease because it, counter-intuitively, represses the transcriptional output of EWS-FLI. This work discovers a previously undescribed transcriptional mechanism that promotes cancer.
Nature Communications
Chromatin Complex Dependencies Reveal Targeting Opportunities in Leukemia
Najm FJ, DeWeirdt P, Moore MM, Bevill SM, El Farran CA, Macias KA, Hegde M, Waterbury AL,
Liau BB, van Galen P, Doench JG, Bernstein BE
Chromatin regulators are frequently mutated in human cancer and are attractive drug targets. They include diverse proteins that share functional domains and assemble into related multi-subunit complexes. To investigate functional relationships among these regulators, here we apply combinatorial CRISPR knockouts (KOs) to test over 35,000 gene-gene pairings in leukemia cells, using a library of over 300,000 constructs. Top pairs that demonstrate either compensatory non-lethal interactions or synergistic lethality enrich for paralogs and targets that occupy the same protein complex. The screen highlights protein complex dependencies not apparent in single KO screens, for example MCM histone exchange, the nucleosome remodeling and deacetylase (NuRD) complex, and HBO1 (KAT7) complex. We explore two approaches to NuRD complex inactivation. Paralog and non-paralog combinations of the KAT7 complex emerge as synergistic lethal and specifically nominate the ING5 PHD domain as a potential therapeutic target when paired with other KAT7 complex member losses. These findings highlight the power of combinatorial screening to provide mechanistic insight and identify therapeutic targets within redundant networks.
Nature Communications
Epigenomic Charting and Functional Annotation of Risk Loci in Renal Cell Carcinoma
Nassar AH, Abou Alaiwi S, Baca SC, Adib E, Seo JH, Spisak S, El Zarif T, Tisza V, Braun DA, Du H,
He M, Flaifel A, Alchoueiry M, Denize T, Matar SG, Acosta A, Shukla S, Hou Y, Steinharter J, Bouchard G, Berchuck JE, O'Connor E, Bell C, Nuzzo PV, Mary Lee GS, Signoretti S, Hirsch MS, Pomerantz M, Henske E, Gusev A, Choueiri TK, Kwiatkowski DJ, Freedman ML
While the mutational and transcriptional landscapes of renal cell carcinoma (RCC) are well-known, the epigenome is poorly understood. We characterize the epigenome of clear cell (ccRCC), papillary (pRCC), and chromophobe RCC (chRCC) by using ChIP-seq, ATAC-Seq, RNA-seq, and SNP arrays. We integrate 153 individual data sets from 42 patients and nominate 50 histology-specific master transcription factors (MTF) to define RCC histologic subtypes, including EPAS1 and ETS-1 in ccRCC, HNF1B in pRCC, and FOXI1 in chRCC. We confirm histology-specific MTFs via immunohistochemistry including a ccRCC-specific TF, BHLHE41. FOXI1 overexpression with knock-down of EPAS1 in the 786-O ccRCC cell line induces transcriptional upregulation of chRCC-specific genes, TFCP2L1, ATP6V0D2, KIT, and INSRR, implicating FOXI1 as a MTF for chRCC. Integrating RCC GWAS risk SNPs with H3K27ac ChIP-seq and ATAC-seq data reveals that risk-variants are significantly enriched in allelically-imbalanced peaks. This epigenomic atlas in primary human samples provides a resource for future investigation.
New England Journal of Medicine
Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia
Brown JR
BACKGROUND: In a multinational, phase 3, head-to-head trial, ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, was compared with zanubrutinib, a BTK inhibitor with greater specificity, as treatment for relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). In prespecified interim analyses, zanubrutinib was superior to ibrutinib with respect to overall response (the primary end point). Data from the final analysis of progression-free survival are now available.
METHODS: We randomly assigned, in a 1:1 ratio, patients with relapsed or refractory CLL or SLL who had received at least one previous course of therapy to receive zanubrutinib or ibrutinib until the occurrence of disease progression or unacceptable toxic effects. In this final analysis, progression-free survival (a key secondary end point) was assessed with the use of a hierarchical testing strategy to determine whether zanubrutinib was noninferior to ibrutinib. If noninferiority was established, the superiority of zanubrutinib was assessed and claimed if the two-sided P value was less than 0.05.
RESULTS: At a median follow-up of 29.6 months, zanubrutinib was found to be superior to ibrutinib with respect to progression-free survival among 652 patients (hazard ratio for disease progression or death, 0.65; 95% confidence interval, [CI], 0.49 to 0.86; P = 0.002), as assessed by the investigators; the results were similar to those as assessed by an independent-review committee. At 24 months, the investigator-assessed rates of progression-free survival were 78.4% in the zanubrutinib group and 65.9% in the ibrutinib group. Among patients with a 17p deletion, a TP53 mutation, or both, those who received zanubrutinib had longer progression-free survival than those who received ibrutinib (hazard ratio for disease progression or death, 0.53; 95% CI, 0.31 to 0.88); progression-free survival across other major subgroups consistently favored zanubrutinib. The percentage of patients with an overall response was higher in the zanubrutinib group than in the ibrutinib group. The safety profile of zanubrutinib was better than that of ibrutinib, with fewer adverse events leading to treatment discontinuation and fewer cardiac events, including fewer cardiac events leading to treatment discontinuation or death.
CONCLUSIONS: In patients with relapsed or refractory CLL or SLL, progression-free survival was significantly longer among patients who received zanubrutinib than among those who received ibrutinib, and zanubrutinib was associated with fewer cardiac adverse events. (Funded by BeiGene; ALPINE ClinicalTrials.gov number, NCT03734016.).
Proceedings of the National Academy of Sciences of the U.S.A.
Evolution of Nanobodies Specific for BCL11A
Yin M, Izadi M, Tenglin K, Viennet T, Zheng G, Arthanari H, Orkin SH
Transcription factors (TFs) control numerous genes that are directly relevant to many human disorders. However, developing specific reagents targeting TFs within intact cells is challenging due to the presence of highly disordered regions within these proteins. Intracellular antibodies offer opportunities to probe protein function and validate therapeutic targets. Here, we describe the optimization of nanobodies specific for BCL11A, a validated target for the treatment of hemoglobin disorders. We obtained first-generation nanobodies directed to a region of BCL11A comprising zinc fingers 4 to 6 (ZF456) from a synthetic yeast surface display library, and employed error-prone mutagenesis, structural determination, and molecular modeling to enhance binding affinity. Engineered nanobodies recognized ZF6 and mediated targeted protein degradation (TPD) of BCL11A protein in erythroid cells, leading to the anticipated reactivation of fetal hemoglobin (HbF) expression. Evolved nanobodies distinguished BCL11A from its close paralog BCL11B, which shares an identical DNA-binding specificity. Given the ease of manipulation of nanobodies and their exquisite specificity, nanobody-mediated TPD of TFs should be suitable for dissecting regulatory relationships of TFs and gene targets and validating therapeutic potential of proteins of interest.
American Journal of Gastroenterology
Ugai T, Haruki K, Chan AT, Akimoto N, Fujiyoshi K, Nishihara R, Giannakis M, Song M, Nowak JA, Ogino S
Blood Advances
Genomics of PDGFR-Rearranged Hypereosinophilic Syndrome
Rheinbay E, Qi M, Bouyssou J, Lane AA
Cancer Research
Transcriptional Antagonism by CDK8 Inhibition Improves Therapeutic Efficacy of MEK Inhibitors
Malone CF, Kim M, Alexe G, Engel K, Forman AB, Robichaud A, Conway AS, Goodale A, Meyer A, Khalid D, Thayakumar A, Hatcher JM, Piccioni F, Stegmaier K
Cancer Research
JAK-STAT Signaling in Inflammatory Breast Cancer Enables Chemotherapy-Resistant Cell States
Stevens LE, Peluffo G, Qiu X, Temko D, Fassl A, Li Z, Trinh A, Seehawer M, Jovanovic B,
Aleckovic M, Wilde CM, Geck RC, Shu S, Kingston NL, Harper NW, Almendro V, Pyke AL, Egri SB, Papanastasiou M, Clement K, Zhou N, Walker S, Salas J, Frank DA, Meissner A, Jaffe JD, Sicinski P, Toker A, Michor F, Long HW, Overmoyer BA, Polyak K
Chemical Communications
Carrier Protein Mediated Cargo Sensing in Quorum Signal Synthases
Fischer PD, Cox HS 3rd, Matosin S, Arthanari H
European Radiology
Tran NA, Palotai M, Hanna GJ, Schoenfeld JD, Bay CP, Rettig EM, Juliano AF, Kelly HR, Morales Pinzon A, Kann BH, Huang RY, Haddad RI, Guttmann CRG, Guenette JP
Expert Review of Anticancer Therapy
Tolaney SM, Tarantino P
HemaSphere
Interim Positron Emission Tomography During Frontline Chemoimmunotherapy for Follicular Lymphoma
Merryman RW, Redd R, Park H, Spilberg G, Robertson M, Chase M, Jeter E, Ahn IE, Brown JR, Crombie J, Davids MS, Fisher DC, Jacobsen E, Jacobson CA, Kim AI, LaCasce AS, Ng SY, Odejide OO, Parry EM, Armand P, Jacene H
Journal of the American Geriatrics Society
Evaluation of Interdisciplinary Care Pathway Implementation in Older Elective Surgery Patients
Hu FY, Rowe KA, O'Mara LM, Bulger A, Bleday R, Groff MW, Cooper Z, Bernacki RE
Journal of Cancer Research and Clinical Oncology
Sullivan RJ, Cohen JV, Haq R
Journal of Clinical Investigation
YAP1 and WWTR1 Expression Inversely Correlate with Neuroendocrine Markers in Merkel Cell Carcinoma
Frost TC, Gartin AK, Liu M, Dharaneeswaran H, Keskin DB, Wu CJ, Giobbie-Hurder A, Thakuria M, DeCaprio JA
Journal of Gastroenterology
Ugai T, Akimoto N, Haruki K, Chan AT, Nishihara R, Meyerhardt JA, Giannakis M, Song M, Nowak JA, Ogino S
Journal of Nuclear Medicine
Ravi P, Whelpley B, Kelly E, Wolanski A, Ritzer J, Robertson M, Shah H, Morgans AK, Wei XX, Sunkara R, Pomerantz M, Taplin ME, Kilbridge KL, Choudhury AD, Jacene H
Journal of Palliative Medicine
Jain N, Bernacki RE, Lee KA, Siegel JH, Yenulevich EG, Lally KM
Journal of Surgical Oncology
Hong JH, Swami N, Lam MB
JAMA Neurology
Challenges and Opportunities for Clinical Trials in Patients with Glioma
Gonzalez Castro LN, Arrillaga-Romany IC, Batchelor TT
Leukemia
Ryan CE, Tyekucheva S, Hackett LR, Collins MC, Fernandes SM, Ren Y, Zhou Y, McDonough MM, Walker HA, McEwan MR, Abramson JS, Jacobsen ED, LaCasce AS, Fisher DC, Brown JR, Davids MS
Nature Nanotechnology
Molecular Bottlebrush Prodrugs as Mono- and Triplex Combination Therapies for Multiple Myeloma
Detappe A, Nguyen HV, Agius MP, Mathieu C, Su NK, Ghobrial IM, Ghoroghchian PP, Johnson JA
Neuro-Oncology
Aquilanti E, Kageler L, Watson J, Szegletes ZM, Doench JG, Strathdee CA, McFaline Figueroa JR, Ligon K, Beck M, Wen PY, Meyerson M
Oncologist
Buswell L, Fadelu T
Statistics in Medicine
On Assessing Survival Benefit of Immunotherapy Using Long-Term Restricted Mean Survival Time
Horiguchi M, Uno H
Transplantation and Cellular Therapy
Nikiforow S, Frigault MJ