Welcome to Dana-Farber's Research News
April 01, 2024
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
Bae J, Kitayama S, Herbert Z, Daheron L, Kurata K, Keskin DB, Livak K, Li S, Tarannum M, Romee R, Samur M, Munshi NC, Ritz J, Anderson KC
A major hurdle in adoptive T-cell therapy is cell exhaustion and failure to maintain antitumor responses. Here, we introduce an induced pluripotent stem cell (iPSC) strategy for reprogramming and revitalizing precursor exhausted B-cell maturation antigen (BCMA)-specific T cells to effectively target multiple myeloma (MM). Heteroclitic BCMA72-80 (YLMFLLRKI)-specific CD8+ memory cytotoxic T lymphocytes (CTL) were epigenetically reprogrammed to a pluripotent state, developed into hematopoietic progenitor cells (CD34+ CD43+/CD14- CD235a-), differentiated into the T-cell lineage and evaluated for their polyfunctional activities against MM. The final T-cell products demonstrated (1) mature CD8??+ memory phenotype, (2) high expression of activation or costimulatory molecules (CD38, CD28, and 41BB), (3) no expression of immune checkpoint and senescence markers (CTLA4, PD1, LAG3, and TIM3; CD57), and (4) robust proliferation and polyfunctional immune responses to MM. The BCMA-specific iPSC-T cells possessed a single T-cell receptor clonotype with cognate BCMA peptide recognition and specificity for targeting MM. RNA sequencing analyses revealed distinct genome-wide shifts and a distinctive transcriptional profile in selected iPSC clones, which can develop CD8??+ memory T cells. This includes a repertoire of gene regulators promoting T-cell lineage development, memory CTL activation, and immune response regulation (LCK, IL7R, 4-1BB, TRAIL, GZMB, FOXF1, and ITGA1). This study highlights the potential application of iPSC technology to an adaptive T-cell therapy protocol and identifies specific transcriptional patterns that could serve as a biomarker for selection of suitable iPSC clones for the successful development of antigen-specific CD8??+ memory T cells to improve the outcome in patients with MM.
Blood
Low-Frequency Inherited Complement Receptor Variants are Associated with Purpura Fulminans
Bendapudi PK, Nazeen S, Ryu J, Söylemez O, Robbins A, Rouaisnel B, O'Neil JK, Pokhriyal R, Yang M, Colling M, Bouzinier M, Tomczak L, Collier L, Barrios D, Toth-Petroczy A, Krier J, Fieg E, Dzik WH, Pozdnyakova O, Nardi V, Maas R, Sunyaev S, Losman JA
Extreme disease phenotypes can provide key insights into the pathophysiology of common conditions, but studying such cases is challenging due to their rarity and the limited statistical power of existing methods. Herein, we used a novel approach to pathway-based mutational burden testing, the rare variant trend test (RVTT), to investigate genetic risk factors for an extreme form of sepsis-induced coagulopathy, infectious purpura fulminans (PF). In addition to prospective patient sample collection, we electronically screened over 10.4 million medical records from 4 large hospital systems and identified historical cases of PF for which archived specimens were available to perform germline whole-exome sequencing. We found a significantly increased burden of low-frequency, putatively function-altering variants in the complement system in patients with PF compared with unselected patients with sepsis (P = .01). A multivariable logistic regression analysis found that the number of complement system variants per patient was independently associated with PF after controlling for age, sex, and disease acuity (P = .01). Functional characterization of PF-associated variants in the immunomodulatory complement receptors CR3 and CR4 revealed that they result in partial or complete loss of anti-inflammatory CR3 function and/or gain of proinflammatory CR4 function. Taken together, these findings suggest that inherited defects in CR3 and CR4 predispose to the maladaptive hyperinflammation that characterizes severe sepsis with coagulopathy.
Cancer Cell
Revisiting TNM Staging for EBV-Related Nasopharyngeal Carcinoma
Dennis M, Haddad R
Advances in imaging and novel treatment approaches might have outpaced the prognostic capabilities of the current AJCC/UICC TNM 8th edition for staging nasopharyngeal carcinoma (NPC). In this issue of Cancer Cell, Du et al. propose a new TNM-9 classification that incorporates these updates.
Cancer Discovery
Choueiri TK, Braun DA
The phase III JAVELIN Renal 101 trial demonstrated prolonged progression-free survival (PFS) in patients (N = 886) with advanced renal cell carcinoma treated with first-line avelumab + axitinib (A+Ax) versus sunitinib. We report novel findings from integrated analyses of longitudinal blood samples and baseline tumor tissue. PFS was associated with elevated lymphocyte levels in the sunitinib arm and an abundance of innate immune subsets in the A+Ax arm. Treatment with A+Ax led to greater T-cell repertoire modulation and less change in T-cell numbers versus sunitinib. In the A+Ax arm, patients with tumors harboring mutations in ?2 of 10 previously identified PFS-associated genes (double mutants) had distinct circulating and tumor-infiltrating immunologic profiles versus those with wild-type or single-mutant tumors, suggesting a role for non-T-cell-mediated and non-natural killer cell-mediated mechanisms in double-mutant tumors. We provide evidence for different immunomodulatory mechanisms based on treatment (A+Ax vs. sunitinib) and tumor molecular subtypes.
SIGNIFICANCE: Our findings provide novel insights into the different immunomodulatory mechanisms governing responses in patients treated with avelumab (PD-L1 inhibitor) + axitinib or sunitinib (both VEGF inhibitors), highlighting the contribution of tumor biology to the complexity of the roles and interactions of infiltrating immune cells in response to these treatment regimens. This article is featured in Selected Articles from This Issue, p. 384.
Cancer Discovery
Noninvasive Detection of Neuroendocrine Prostate Cancer through Targeted Cell-free DNA Methylation
Mizuno K, Ku SY, Rothmann E, Freeman D, Beltran H
Castration-resistant prostate cancer (CRPC) is a heterogeneous disease associated with phenotypic subtypes that drive therapy response and outcome differences. Histologic transformation to castration-resistant neuroendocrine prostate cancer (CRPC-NE) is associated with distinct epigenetic alterations, including changes in DNA methylation. The current diagnosis of CRPC-NE is challenging and relies on metastatic biopsy. We developed a targeted DNA methylation assay to detect CRPC-NE using plasma cell-free DNA (cfDNA). The assay quantifies tumor content and provides a phenotype evidence score that captures diverse CRPC phenotypes, leveraging regions to inform transcriptional state. We tested the design in independent clinical cohorts (n = 222 plasma samples) and qualified it achieving an AUC > 0.93 for detecting pathology-confirmed CRPC-NE (n = 136). Methylation-defined cfDNA tumor content was associated with clinical outcomes in two prospective phase II clinical trials geared towards aggressive variant CRPC and CRPC-NE. These data support the application of targeted DNA methylation for CRPC-NE detection and patient stratification.
SIGNIFICANCE: Neuroendocrine prostate cancer is an aggressive subtype of treatment-resistant prostate cancer. Early detection is important, but the diagnosis currently relies on metastatic biopsy. We describe the development and validation of a plasma cell-free DNA targeted methylation panel that can quantify tumor fraction and identify patients with neuroendocrine prostate cancer noninvasively. This article is featured in Selected Articles from This Issue, p. 384.
Journal of Clinical Oncology
Cannabis and Cannabinoids in Adults with Cancer: ASCO Guideline
Braun IM, Chai PR
PURPOSE: To guide clinicians, adults with cancer, caregivers, researchers, and oncology institutions on the medical use of cannabis and cannabinoids, including synthetic cannabinoids and herbal cannabis derivatives; single, purified cannabinoids; combinations of cannabis ingredients; and full-spectrum cannabis.
METHODS: A systematic literature review identified systematic reviews, randomized controlled trials (RCTs), and cohort studies on the efficacy and safety of cannabis and cannabinoids when used by adults with cancer. Outcomes of interest included antineoplastic effects, cancer treatment toxicity, symptoms, and quality of life. PubMed and the Cochrane Library were searched from database inception to January 27, 2023. ASCO convened an Expert Panel to review the evidence and formulate recommendations.
RESULTS: The evidence base consisted of 13 systematic reviews and five additional primary studies (four RCTs and one cohort study). The certainty of evidence for most outcomes was low or very low.
RECOMMENDATIONS: Cannabis and/or cannabinoid access and use by adults with cancer has outpaced the science supporting their clinical use. This guideline provides strategies for open, nonjudgmental communication between clinicians and adults with cancer about the use of cannabis and/or cannabinoids. Clinicians should recommend against using cannabis or cannabinoids as a cancer-directed treatment unless within the context of a clinical trial. Cannabis and/or cannabinoids may improve refractory, chemotherapy-induced nausea and vomiting when added to guideline-concordant antiemetic regimens. Whether cannabis and/or cannabinoids can improve other supportive care outcomes remains uncertain. This guideline also highlights the critical need for more cannabis and/or cannabinoid research. Additional information is available at www.asco.org/supportive-care-guidelines.
Journal of Clinical Oncology
Jänne PA
PURPOSE: We report CNS efficacy of first-line osimertinib plus chemotherapy versus osimertinib monotherapy in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) from the phase III FLAURA2 study according to baseline CNS metastasis status.
METHODS: Patients were randomly assigned to osimertinib plus platinum-pemetrexed (combination) or osimertinib monotherapy until disease progression or discontinuation. Brain scans were performed in all patients at baseline and progression and at scheduled assessments until progression for patients with baseline CNS metastases; scans were assessed by neuroradiologist CNS blinded independent central review (BICR).
RESULTS: On the basis of baseline CNS BICR, 118 of 279 (combination) and 104 of 278 (monotherapy) randomly assigned patients had ?one measurable and/or nonmeasurable CNS lesion and were included in the CNS full analysis set (cFAS); 40 of 118 and 38 of 104 had ?one measurable target CNS lesion and were included in the post hoc CNS evaluable-for-response set (cEFR). In the cFAS, the hazard ratio (HR) for CNS progression or death was 0.58 (95% CI, 0.33 to 1.01). In patients without baseline CNS metastases, the HR for CNS progression or death was 0.67 (95% CI, 0.43 to 1.04). In the cFAS, CNS objective response rates (ORRs; 95% CI) were 73% (combination; 64 to 81) versus 69% (monotherapy; 59 to 78); 59% versus 43% had CNS complete response (CR). In the cEFR, CNS ORRs (95% CI) were 88% (73 to 96) versus 87% (72 to 96); 48% versus 16% had CNS CR.
CONCLUSION: Osimertinib plus platinum-pemetrexed demonstrated improved CNS efficacy compared with osimertinib monotherapy, including delaying CNS progression, irrespective of baseline CNS metastasis status. These data support this combination as a new first-line treatment for patients with EGFR-mutated advanced NSCLC, including those with CNS metastases.
Journal of Clinical Oncology
Burstein HJ
ASCO Rapid Recommendation Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only).
Journal of Clinical Oncology
Wagner AJ, Hornick JL, Du H, Kwiatkowski DJ
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.nab-Sirolimus is approved in the United States for the treatment of metastatic or locally advanced malignant perivascular epithelioid cell tumor (PEComa) on the basis of the primary analysis results of the phase II Advanced Malignant Perivascular Epithelioid Cell Tumors (AMPECT) trial (ClinicalTrials.gov identifier: NCT02494570). Results from the primary analysis were previously published; however, the median duration of response (mDOR) had not been reached at that time. Here, 3 years after the primary analysis, we report final efficacy and safety data (data cutoff: April 29, 2022). At study completion, the confirmed overall response rate (by independent radiologist review using RECIST v1.1) was 38.7% (95% CI, 21.8 to 57.8), with an additional converted confirmed complete response (n = 2). Median progression-free survival remained the same at 10.6 months (95% CI, 5.5 to 41.2). The mDOR was reached at 39.7 months (95% CI, 6.5 to not reached [NR]), and the median overall survival at completion was 53.1 months (95% CI, 22.2 to NR). The most common treatment-related adverse events (TRAEs) were stomatitis (82.4%) and fatigue and rash (each 61.8%). No new or unexpected adverse events occurred, and no grade ?4 TRAEs were reported. These results highlight the long-term clinical benefit of nab-sirolimus in patients with advanced malignant PEComa, with a DOR of >3 years.
Journal of the National Cancer Institute
Paudel R, Enzinger AC, Uno H, Cronin C, Hassett MJ
BACKGROUND: Optimal methods for deploying electronic patient-reported outcomes (ePROs) to manage symptoms in routine oncologic practice remain uncertain. The eSyM symptom management program asks chemotherapy and surgery patients to self-report 12 symptoms regularly. Feedback from nurses and patients led to changing the recall period from the past 7?days to the past 24?hours.
METHODS: Using questionnaires submitted during the 16-weeks surrounding the recall period change, we assessed the likelihood of reporting a severe, or a moderate-severe, symptom across all 12 symptoms and separately for the 5 most prevalent symptoms. Interrupted time series analyses modeled the effects of the change using generalized linear mixed-effects models. Surgery and chemotherapy cohorts were analyzed separately. Study-wide effects were estimated using a meta-analysis method.
RESULTS: In total, 1,692 patients from 6 institutions submitted 7,823 eSyM assessments during the 16-weeks surrounding the recall period change. Shortening the recall period was associated with lower odds of severe symptom reporting in the surgery cohort (OR 0.65; 95% CI 0.46 to 0.93; p?=?.02) and lower odds of moderate-severe symptom reporting in the chemotherapy cohort (OR 0.83, 95% CI 0.71 to 0.97; p?=?.02). Among the most prevalent symptoms, 24-hour recall was associated with lower rate of reporting post-operative constipation, but no differences in reporting rates for other symptoms.
CONCLUSION: A shorter recall period was associated with a reduction in the proportion of patients reporting moderate-severe symptoms. The optimal recall period may vary depending on whether ePROs are collected for active symptom management, as a clinical trial endpoint, or another purpose. (Clinicaltrails.gov (NCT03850912).
Journal of the National Cancer Institute
Gonzalo-Encabo P, Dieli-Conwright CM
BACKGROUND: Postmenopausal women with cancer experience an accelerated physical dysfunction beyond that expected through aging alone due to cancer and its treatments. The aim of this study is to determine whether declines in physical function after cancer diagnosis are associated with all-cause mortality and cancer-specific mortality.
METHODS: This prospective cohort study included 8,068 postmenopausal women enrolled in the Women's Health Initiative (WHI) who were diagnosed with cancer and had physical function assessed within 1-year of cancer diagnosis. Self-reported physical function was measured using the 10-item physical function subscale of the RAND 36-Item Health Survey. Cause of death was determined by medical record review with central adjudication and linkage to the National Death Index. Death was adjudicated through February 2022.
RESULTS: Over a median follow-up of 7.7?years from cancer diagnosis 3,316 (41.1%) women died. Our results showed that for every 10% decline in the physical function score after cancer diagnosis, all-cause mortality and cancer-specific mortality were significantly reduced by 12% (HR, 0.88; 95% CI, 0.87 to 0.89) and (HR, 0.88; 95%CI, 0.86 to 0.91), respectively. Further categorical analyses showed a significant dose-response relationship between post-diagnosis physical function categories and mortality outcomes (trend test P?
JAMA Oncology
Advancing Truth in Oncology by Complementing Clinical Trials with Evidence from Clinical Practice
Sharon E
Despite the increasing complexity of cancer clinical trials, the most successful trials often answer simple questions of efficacy for populations of patients with the most generalizable characteristics and adequate organ function. Unfortunately, as a result, specific populations of patients, such as older adults, who may be frail or have other comorbid conditions, can often be overlooked. In this issue of JAMA Oncology, the case series by Tsukita et al presented the results of an analysis from an impressive network of Japanese oncology sites, collating data that answer an important clinical question of relevance to patients with non–small cell lung cancer who are older than 75 years of age. These types of efforts are needed by both patients and clinicians and are often sorely lacking in oncology.
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.
Lancet Oncology
Nikiforow S, Prockop S
BACKGROUND: Survival in Epstein-Barr virus (EBV)-positive post-transplant lymphoproliferative disease following haematopoietic stem-cell transplant (HSCT) or solid organ transplant (SOT) is poor after failure of initial therapy, indicating an urgent need for therapies for this ultra-rare disease. With recent EU marketing authorisation, tabelecleucel is the first off-the-shelf, allogeneic, EBV-specific T-cell immunotherapy to receive approval for treatment of relapsed or refractory EBV-positive post-transplant lymphoproliferative disease. We aimed to determine the clinical benefit of tabelecleucel in patients with relapsed or refractory EBV-positive post-transplant lymphoproliferative disease following HSCT or SOT.
METHODS: In this global, multicentre, open-label, phase 3 trial, eligible patients (of any age) had biopsy-proven EBV-positive post-transplant lymphoproliferative disease, disease that was relapsed or refractory to rituximab after HSCT and rituximab with or without chemotherapy after SOT, and partially HLA-matched and appropriately HLA-restricted tabelecleucel available. Patients received tabelecleucel administered intravenously at 2?×?106 cells per kg on days 1, 8, and 15 in 35-day cycles and are assessed for up to 5 years for survival post-treatment initiation. The primary endpoint was objective response rate. All patients who received at least one dose of tabelecleucel were included in safety and efficacy analyses. This trial is registered with ClinicalTrials.gov, NCT03394365, and is ongoing.
FINDINGS: From June 27, 2018, to Nov 5, 2021, 63 patients were enrolled, of whom 43 (24 [56%] male and 19 [44%] female) were included, 14 had prior HSCT, 29 had SOT. Seven (50%, 95% CI 23-77) of 14 participants in the HSCT group and 15 (52%, 33-71) of 29 participants in the SOT group had an objective response, with a median follow-up of 14·1 months (IQR 5·7-23·9) and 6·0 months (1·8-18·4), respectively. The most common grade 3 or 4 treatment-emergent adverse events were disease progression (in four [29%] of 14 in HSCT and eight [28%] of 29 in SOT) and decreased neutrophil count (in four [29%] of 14 in HSCT and four [14%] of 29 in SOT). Treatment-emergent serious adverse events were reported in 23 (53%) of 43 patients and fatal treatment-emergent adverse events in five (12%); no fatal treatment-emergent adverse event was treatment-related. There were no reports of tumour flare reaction, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, transmission of infectious diseases, marrow rejection, or infusion reactions. No events of graft-versus-host disease or SOT rejection were reported as related to tabelecleucel.
INTERPRETATION: Tabelecleucel provides clinical benefit in patients with relapsed or refractory EBV-positive post-transplant lymphoproliferative disease, for whom there are no other approved therapies, without evidence of safety concerns seen with other adoptive T-cell therapies. These data represent a potentially transformative and accessible treatment advance for patients with relapsed or refractory disease with few treatment options.
FUNDING: Atara Biotherapeutics.
Nature
Deciphering Cell States and Genealogies of Human Haematopoiesis
Weng C, Yu F, Poeschla M, Liggett LA, Wahlster L, Caulier A, Martin-Rufino JD, Hammond A, Ssozi D, Bueno R, Mallidi H, Kreso A, Escabi J, Hormoz S, van Galen P, Weissman JS, Sankaran VG
The human blood system is maintained through the differentiation and massive amplification of a limited number of long-lived haematopoietic stem cells (HSCs)1. Perturbations to this process underlie diverse diseases, but the clonal contributions to human haematopoiesis and how this changes with age remain incompletely understood. Although recent insights have emerged from barcoding studies in model systems2-5, simultaneous detection of cell states and phylogenies from natural barcodes in humans remains challenging. Here we introduce an improved, single-cell lineage-tracing system based on deep detection of naturally occurring mitochondrial DNA mutations with simultaneous readout of transcriptional states and chromatin accessibility. We use this system to define the clonal architecture of HSCs and map the physiological state and output of clones. We uncover functional heterogeneity in HSC clones, which is stable over months and manifests as both differences in total HSC output and biases towards the production of different mature cell types. We also find that the diversity of HSC clones decreases markedly with age, leading to an oligoclonal structure with multiple distinct clonal expansions. Our study thus provides a clonally resolved and cell-state-aware atlas of human haematopoiesis at single-cell resolution, showing an unappreciated functional diversity of human HSC clones and, more broadly, paving the way for refined studies of clonal dynamics across a range of tissues in human health and disease.
Abdominal Radiology
MRI, Clinical, and Radiomic Models for Differentiation of Uterine Leiomyosarcoma and Leiomyoma
Roller LA, Wan Q, Qin L, Burk KS, Guo Y, Shinagare AB
Annals of Surgical Oncology
Long-Term Patient-Reported Arm Symptoms in Breast Cancer Survivors
Laws A, Grossmith S, Hughes M, Lin NU, Mittendorf EA, Eliassen AH, King TA, Dominici LS
Arthritis Care and Research
Goldschen L, Peng CS, Mufson MJ, Feldman CH, Case SM, Costenbader KH, Amonoo HL
Arthritis and Rheumatology
Association of Somatic TET2 Mutations with Giant Cell Arteritis
Robinette ML, Weeks LD, Kramer RJ, Agrawal M, Gibson CJ, Yu Z, Sekar A, Mehta A, Niroula A, Brown JT, McDermott GC, Reshef ER, Lu JE, Liou VD, Chiou CA, Natarajan P, Freitag SK, Rao DA, Ebert BL
Blood Cancer Discovery
Acquired Multidrug Resistance in AML Is Caused by Low Apoptotic Priming in Relapsed Myeloblasts
Olesinski EA, Pioso MS, Yilma B, Bohl S, Ryan JA, Malani D, Luskin MR, Adamia S, Weinstock DM, Garcia JS, Letai A
Blood Cancer Discovery
Round Table Discussion on Optimal Clinical Trial Design in Precursor Multiple Myeloma
Ghobrial IM, Getz G, Nadeem O, O'Donnell E, Sklavenitis-Pistofidis R, Sperling AS, Munshi NC, Anderson KC
Blood Cancer Discovery
Bhola PD, Letai A
BMC Medical Informatics and Decision Making
Halpenny B, Abrahm JL, Ligibel J, Enzinger A, Cooley ME
Breast Cancer Research Treatment
Lin NU, Leone JP
Cancer
Meyerhardt J, Ng K, Partridge AH, George S
Cancer
Mullen EA
Cancer
Walburn T, Loffredo M, McMahon E, Orio PF, Nguyen PL, D'Amico AV, Sayan M
Cancer
Mullen EA
Cancer Research
A Benzarone Derivative Inhibits EYA to Suppress Tumor Growth in SHH Medulloblastoma
Hwang GH, Pazyra-Murphy MF, Seo HS, Dhe-Paganon S, Stopka SA, DiPiazza M, Sutter N, Gero TW, Volkert A, Ombelets L, Dittemore G, Rees MG, Ronan MM, Roth JA, Agar NYR, Scott DA, Segal RA
Cells
Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy
Maia A, Tarannum M, Piccinelli S, Romee R
Clinical Cancer Research
Corcoran RB, Do KT, Cleary JM, Parikh AR, Yeku OO, Xiong N, Weekes CD, Ahronian LG, Tian J, Norden BL, Michel AG, Van Seventer EE, Siravegna G, Camphausen K, Chi G, Fetter IJ, Brugge JS, Penson RT, Juric D, Flaherty KT, Sullivan RJ, Clark JW, Heist RS, Matulonis UA, Liu JF, Shapiro GI
Clinical Lymphoma, Myeloma, and Leukemia
Shimony S, Luskin MR
Communications Medicine
Deep Learning Analysis of Epicardial Adipose Tissue to Predict Cardiovascular Risk in Heavy Smokers
Foldyna B, Hadzic I, Zeleznik R, Langenbach MC, Raghu VK, Mayrhofer T, Lu MT, Aerts HJWL
Current Opinion in Hematology
The Future of HOXA- Expressing Leukemias: Menin Inhibitor Response and Resistance
Wenge DV, Armstrong SA
Current Opinion in Nephrology and Hypertension
Onconephrology: Mitigation of Renal Injury in Chemotherapy Administration
Selamet U
EClinicalMedicine
O'Neill AF
European Journal of Cancer
Tolaney SM
European Urology Open Science
Integrative Analysis of Germline Rare Variants in Clear and Non-clear Cell Renal Cell Carcinoma
Han SH, Camp SY, Chu H, Collins R, Gillani R, Park J, Bakouny Z, Ricker CA, Reardon B, Labaki C, Choueiri TK, AlDubayan SH, Van Allen EM
Frontier Oncology
Choueiri TK
Gut
Protein Biomarkers and Alternatively Methylated Cell-Free DNA Detect Early Stage Pancreatic Cancer
Wang QL, Zhang J, Supplee JG, Brais LK, Nowak J, Yuan C, Loftus M, Babic A, Boos N, Jajoo K, Lee L, Clancy TE, Rubinson DA, Ng K, Aguirre AJ, Jänne PA, Bardeesy N, Bullock AJ, Paweletz CP, Wolpin BM
Journal of the American College of Surgeons
Jin Q, Waks AG, Spring LM, Wrabel E, Tayob N, King TA, Metzger-Filho O
Journal of the American College of Surgeons
Mullen EA
Journal of Cell Biology
PC4: A New Regulator of Cyclin D1 Transcript Levels
Sicinski P
Journal of the European Academy of Dermatology and Venereology
Kim EY, Liu M, Giobbie-Hurder A, Bahar F, Khaddour K, Silk AW, Thakuria M
Journal of Nuclear Medicine
The Current and Future Roles of Precision Oncology in Advanced Breast Cancer
Jacene H
Journal of Thoracic Oncology
MUC1-C Is a Common Driver of Acquired Osimertinib Resistance in NSCLC
Haratake N, Ozawa H, Morimoto Y, Yamashita N, Daimon T, Bhattacharya A, Wang K, Nakashoji A, Isozaki H, Hata AN, Kufe D
Journal of Women’s Health
Women's Information Needs and Educational Preferences Regarding Lung Cancer Screening
Warner ET, Revette A, Restrepo E, Lathan CS
JCO Oncology Practice
Cannabis and Cannabinoids in Adults with Cancer: ASCO Guideline Q&A
Braun IMlopis P, Agudo J
JCO Oncology Practice
Kelkar AH, Hantel A, Koranteng E, Cutler CS, Hammer MJ, Abel GA
JCO Precision Oncology
Kehl KL, Newcomb A
JMIR Human Factors
The Temperature Feature of ChatGPT: Modifying Creativity for Clinical Research
Davis J, Durieux BN, Lindvall Cgudo J
JMIR Research Protocol
Lee DJ, O'Donnell EK, Raje N, Panaroni C, Redd R, Ligibel J, Nadeem O, Ghobrial IM, Marinac CR
Leukemia
Inherent Genome Instability Underlies Trisomy 21-Associated Myeloid Malignancies
Chen CC, Perry JA, Khalid D, Pikman Y, Rowe RG
Leukemia
Lin S, Schneider C, Su AH, Alexe G, Root DE, Stegmaier K
Leukemia
Flamand Y, Shimony S, Place AE, Silverman LB, Vrooman LM, Brunner AM, Sallan SE, Wadleigh M, Stone RM, DeAngelo DJ, Luskin MR
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
NAR Cancer
The ORFIUS Complex Regulates ORC2 Localization at Replication Origins
Yang Z, Mogre S, He R, Berdan EL, Ho Sui SJ, Hill SJ
Nature Methods
scPerturb: Harmonized Single-Cell Perturbation Data
Green TD, Shen C, Min J, Yuan B, Marks DS, Luna A, Sander C
Nature Nanotechnology
Fine Tuning of CpG Spatial Distribution with DNA Origami for Improved Cancer Vaccination
Zeng YC, Young OJ, Wintersinger CM, Anastassacos FM, MacDonald JI, Isinelli G, Dellacherie MO, Sobral M, Bai H, Graveline AR, Vernet A, Sanchez M, Mulligan K, Ferrante TC, Keskin DB, Fell GG, Neuberg D, Wu CJ, Mooney DJ, Kwon IC, Ryu JH, Shih WM
Nature Reviews Cancer
Approaching Cancer During Pregnancy
Varella L, Partridge AH
Oncogene
Serafim RB, Qi H, Parasuram R, Price BD
Open Forum Infectious Diseases
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