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Dana-Farber Research Publication 5.1.2022

Welcome to Dana-Farber's Research News

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May 1, 2022

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

Single-Cell Analysis Reveals Immune Dysfunction from the Earliest Stages of CLL That Can Be Reversed by Ibrutinib

Purroy N, Tong YE, Lemvigh CK, Cieri N, Li S, Parry EM, Zhang W, Livak KJ, Kharchenko PV, Neuberg DS, Olsen LR, Gohil SH, Wu CJ

Chronic lymphocytic leukemia (CLL) is characterized by a clonal expansion of mature CD19+CD5+ B cells, which are highly dependent on microenvironmental cues for their survival. This common adult leukemia is preceded by a precursor phase termed monoclonal B-cell lymphocytosis (MBL), which has been characterized as indistinguishable from CLL at the genetic, transcriptomic, and epigenomic level. However, how leukemia cells coevolve with immune cells in their circulating microenvironment during the onset of MBL and upon progression to CLL remains incompletely characterized. Recently, single-cell transcriptome sequencing (scRNA-seq) approaches have transformed our ability to gain a comprehensive evaluation of the spectrum of immune cells within the tumor microenvironment and of their potential cross talk with cancer cells.


 

Cancer Discovery

Classification of KRAS-Activating Mutations and the Implications for Therapeutic Intervention

Johnson C, Burkhart DL, Haigis KM

Members of the family of RAS proto-oncogenes, discovered just over 40 years ago, were among the first cancer-initiating genes to be discovered. Of the three RAS family members, KRAS is the most frequently mutated in human cancers. Despite intensive biological and biochemical study of RAS proteins over the past four decades, we are only now starting to devise therapeutic strategies to target their oncogenic properties. Here, we highlight the distinct biochemical properties of common and rare KRAS alleles, enabling their classification into functional subtypes. We also discuss the implications of this functional classification for potential therapeutic avenues targeting mutant subtypes.

SIGNIFICANCE: Efforts in the recent past to inhibit KRAS oncogenicity have focused on kinases that function in downstream signal transduction cascades, although preclinical successes have not translated to patients with KRAS-mutant cancer. Recently, clinically effective covalent inhibitors of KRASG12C have been developed, establishing two principles that form a foundation for future efforts. First, KRAS is druggable. Second, each mutant form of KRAS is likely to have properties that make it uniquely druggable.


 

Cancer Discovery

Cancer Discovery Sunvozertinib, a Selective EGFR Inhibitor for Previously Treated Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations

Jänne PA

Epidermal growth factor receptor exon 20 insertion mutations (EGFR exon20ins) are detected in approximately 2% of patients with non-small cell lung cancer (NSCLC). Due to lack of effective therapy, the prognosis of these patients was poor. Sunvozertinib (DZD9008) was designed as an oral, potent, irreversible and selective EGFR tyrosine kinase inhibitor, showing activity against EGFR exon20ins and other mutations. In both cell lines and xenograft models, sunvozertinib shows potent antitumor activity. In the two ongoing phase 1 clinical studies, sunvozertinib was tolerated up to 400 mg once daily. The most common drug-related adverse events included diarrhea and skin rash. Antitumor efficacy was observed at the doses of 100 mg and above in patients with EGFR exon20ins NSCLC across different subtypes, with prior amivantamab treatment as well as with baseline brain metastasis. The median duration of response (DoR) has not been reached.


 

Cancer Discovery

Unleashing Cell-Intrinsic Inflammation as a Strategy to Kill AML Blasts

Ellegast JM, Alexe G, Hamze A, Lin S, Uckelmann HJ, Rauch PJ, Pimkin M, Ross LS, Robichaud AL, Saur Conway A, Khalid D, Perry JA, Pikman Y, Orkin SH, Stegmaier K

Leukemic blasts are immune cells gone awry. We hypothesized that dysregulation of inflammatory pathways contributes to the maintenance of their leukemic state and can be exploited as a cell-intrinsic, self-directed immunotherapy. To this end, we applied genome-wide screens to discover genetic vulnerabilities in acute myeloid leukemia (AML) cells implicated in inflammatory pathways. We identified the immune modulator interferon regulatory factor 2 binding protein 2 (IRF2BP2) as a selective AML dependency. We validated AML cell dependency on IRF2BP2 with genetic and protein degradation approaches in vitro and genetically in vivo. Chromatin and global gene expression studies demonstrated that IRF2BP2 represses IL-1B/TNFa signaling via NF-?B, and IRF2BP2 perturbation results in an acute inflammatory state leading to AML cell death. These findings elucidate a hitherto unexplored AML dependency, reveal cell-intrinsic inflammatory signaling as a mechanism priming leukemic blasts for regulated cell death, and establish IRF2BP2-mediated transcriptional repression as a mechanism for blast survival.


 

Journal of Clinical Oncology

Naïve T-Cell Depletion to Prevent GVHD: Searching for a Better Mousetrap

Soiffer RJ

In the article that accompanies this editorial, Bleakley et al1 summarize their experience with three separate trials demonstrating that depletion of naïve CD45RA+ T cells from donor grafts before allogeneic hematopoietic cell transplantation is associated with very low rates of chronic graft versus host disease (cGVHD) and nonrelapse mortality (NRM). The rate of moderate-severe cGVHD in the 138 patients reported in the current article was very low (1%) with very few patients requiring long-term immune suppression. Although the rate of grade II acute GVHD was high, grade III-IV acute GVHD was observed in only 4% of patients. Most notably, the NRM was 8% at 3 years, relapse rate 23%, overall survival (OS) 78%, and GVHD-free relapse-free survival (GRFS) 68%.


 

Journal of Clinical Oncology

Yin and Yang of Psychological Health in the Cancer Experience: Does Positive Psychology Have a Role?

Amonoo HL, El-Jawahri A, Deary EC, Traeger LN, Cutler CS, Antin JA, Huffman JC

Positive psychological health is crucial to optimal clinical outcomes across the cancer care continuum, from prevention and risk reduction to palliative care and survivorship. Yet, the positive psychological factors that affect morbidity and mortality have not been extensively studied in diverse oncologic populations compared with other medical populations—although they could be extremely influential in a cancer population facing a life-threatening diagnosis. Positive psychological well-being (PPWB), a broad construct defined as “the positive cognitions, feelings, and strategies individuals use to evaluate their life favorably and function well,” includes indicators such as positive affect, gratitude, optimism, happiness, and life purpose. Although PPWB coexists with symptoms of distress, it is not simply the opposite of distress. For example, optimism and depression are only modestly inversely correlated. Many studies in medical populations have found that the beneficial effects of positive psychological health on clinical outcomes are independent of the adverse effects of negative psychological conditions like depression on clinical outcomes. Hence, the primary focus of alleviating symptoms of distress and psychiatric disorders to achieve optimal psychological health in oncology populations ignores an essential aspect of well-being: overcoming adversity and accentuating life-affirming perspectives that may enhance the positive aspects of well-being. Importantly, supporting PPWB should not be confused with the tyranny of positive thinking (ie, where patients feel pressured to think positively and may believe that failure to think positively is a character flaw that can lead to poor clinical outcomes and disease setbacks).


 

Molecular Cell

The FUS::DDIT3 Fusion Oncoprotein Inhibits BAF Complex Targeting and Activity in Myxoid Liposarcoma

Zullow HJ, Sankar A, Samé Guerra DD, D'Avino AR, Collings CK, Liang Y, Qi J, Kadoch C

Mammalian SWI/SNF (mSWI/SNF or BAF) ATP-dependent chromatin remodeling complexes play critical roles in governing genomic architecture and gene expression and are frequently perturbed in human cancers. Transcription factors (TFs), including fusion oncoproteins, can bind to BAF complex surfaces to direct chromatin targeting and accessibility, often activating oncogenic gene loci. Here, we demonstrate that the FUS::DDIT3 fusion oncoprotein hallmark to myxoid liposarcoma (MLPS) inhibits BAF complex-mediated remodeling of adipogenic enhancer sites via sequestration of the adipogenic TF, CEBPB, from the genome. In mesenchymal stem cells, small-molecule inhibition of BAF complex ATPase activity attenuates adipogenesis via failure of BAF-mediated DNA accessibility and gene activation at CEBPB target sites. BAF chromatin occupancy and gene expression profiles of FUS::DDIT3-expressing cell lines and primary tumors exhibit similarity to SMARCB1-deficient tumor types. These data present a mechanism by which a fusion oncoprotein generates a BAF complex loss-of-function phenotype, independent of deleterious subunit mutations.


 

Nature

Phage Anti-CBASS and Anti-Pycsar Nucleases Subvert Bacterial Immunity

Hobbs SJ, Lu A, Morehouse BR, Schnabel J, Kranzusch PJ

CBASS and Pycsar are anti-phage defense systems in diverse bacteria that use cyclic nucleotide signals to induce cell death and prevent viral propagation. Phages use multiple strategies to defeat host CRISPR and restriction-modification systems3-10, but no mechanisms are known to evade CBASS and Pycsar immunity. Here we show that phages encode anti-CBASS (Acb) and anti-Pycsar (Apyc) proteins that counteract defense by specifically degrading cyclic nucleotide signals that activate host immunity. Using a biochemical screen of 57 phages in E. coli and B. subtilis, we discover Acb1 from phage T4 and Apyc1 from phage SBSphiJ as founding members of distinct families of immune evasion proteins. Crystal structures of Acb1 in complex with 3'3'-cGAMP define a mechanism of metal-independent hydrolysis 3' of adenosine bases, enabling broad recognition and degradation of cyclic di- and trinucleotide CBASS signals. Structures of Apyc1 reveal a metal-dependent cNMP phosphodiesterase that uses relaxed specificity to target Pycsar cyclic pyrimidine mononucleotide signals. We show that Acb1 and Apyc1 block downstream effector activation and protect from CBASS and Pycsar defense in vivo. Active Acb1 and Apyc1 enzymes are conserved in phylogenetically diverse phages, demonstrating cleavage of host cyclic nucleotide signals is a key strategy of immune evasion in phage biology.


 

Nature Biotechnology

Robust Decomposition of Cell Type Mixtures in Spatial Transcriptomics

Cable DM, Murray E, Zou LS, Goeva A, Macosko EZ, Chen F, Irizarry RA

A limitation of spatial transcriptomics technologies is that individual measurements may contain contributions from multiple cells, hindering the discovery of cell-type-specific spatial patterns of localization and expression. Here, we develop robust cell type decomposition (RCTD), a computational method that leverages cell type profiles learned from single-cell RNA-seq to decompose cell type mixtures while correcting for differences across sequencing technologies. We demonstrate the ability of RCTD to detect mixtures and identify cell types on simulated datasets. Furthermore, RCTD accurately reproduces known cell type and subtype localization patterns in Slide-seq and Visium datasets of the mouse brain. Finally, we show how RCTD's recovery of cell type localization enables the discovery of genes within a cell type whose expression depends on spatial environment. Spatial mapping of cell types with RCTD enables the spatial components of cellular identity to be defined, uncovering new principles of cellular organization in biological tissue. RCTD is publicly available as an open-source R package at https://github.com/dmcable/spacexr.


 

Nature Communications

Author Correction: Identification of ADAR1 Adenosine Deaminase Dependency in a Subset of Cancer Cells

Gannon HS, Zou T, Gao GF, Cai D, Choi PS, Ivan AP, Berger AC, Goldstein JT, Cherniack AD, Vazquez F, Tsherniak A, Hahn WC, Meyerson M

Systematic exploration of cancer cell vulnerabilities can inform the development of novel cancer therapeutics. Here, through analysis of genome-scale loss-of-function datasets, we identify adenosine deaminase acting on RNA (ADAR or ADAR1) as an essential gene for the survival of a subset of cancer cell lines. ADAR1-dependent cell lines display increased expression of interferon-stimulated genes. Activation of type I interferon signaling in the context of ADAR1 deficiency can induce cell lethality in non-ADAR1-dependent cell lines. ADAR deletion causes activation of the double-stranded RNA sensor, protein kinase R (PKR). Disruption of PKR signaling, through inactivation of PKR or overexpression of either a wildtype or catalytically inactive mutant version of the p150 isoform of ADAR1, partially rescues cell lethality after ADAR1 loss, suggesting that both catalytic and non-enzymatic functions of ADAR1 may contribute to preventing PKR-mediated cell lethality. Together, these data nominate ADAR1 as a potential therapeutic target in a subset of cancers.


 

Proceedings of the National Academy of Science of the U.S.A.

Sensitivity of VHL Mutant Kidney Cancers to HIF2 Inhibitors does not Require an Intact p53 Pathway

Stransky LA, Vigeant SM, Huang B, West D, Denize T, Walton E, Signoretti S, Kaelin WG Jr

SignificanceVHL tumor suppressor gene inactivation is a hallmark of clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, and promotes tumor growth by stabilizing the hypoxia-inducible factor 2 (HIF2) transcription factor. HIF2 inhibitors appear to be helpful for some, but not all, ccRCC patients in clinical trials. Previous preclinical and clinical data suggested that only ccRCCs that can activate the p53 tumor suppressor in response to DNA damage would respond to HIF2 inhibitors. Here, we show that an intact p53 pathway is neither necessary nor sufficient for the sensitivity of ccRCCs to HIF2 inhibitors, suggesting that it would be premature to use p53 status to determine which ccRCC patients should be treated with a HIF2 inhibitor.


 

Science

Genome-Wide Analysis of Somatic Noncoding Mutation Patterns in Cancer

Dietlein F, Wang AB, Fagre C, Tang A, Sunyaev SR, Neal JT, Van Allen EM

We established a genome-wide compendium of somatic mutation events in 3949 whole cancer genomes representing 19 tumor types. Protein-coding events captured well-established drivers. Noncoding events near tissue-specific genes, such as ALB in the liver or KLK3 in the prostate, characterized localized passenger mutation patterns and may reflect tumor-cell-of-origin imprinting. Noncoding events in regulatory promoter and enhancer regions frequently involved cancer-relevant genes such as BCL6, FGFR2, RAD51B, SMC6, TERT, and XBP1 and represent possible drivers. Unlike most noncoding regulatory events, XBP1 mutations primarily accumulated outside the gene's promoter, and we validated their effect on gene expression using CRISPR-interference screening and luciferase reporter assays. Broadly, our study provides a blueprint for capturing mutation events across the entire genome to guide advances in biological discovery, therapies, and diagnostics.


 

Academic Radiology

AMSER Rad Path Case of the Month: Effect of Case-based Integration of Radiology and Pathology on Medical Student Education and Interdisciplinary Collaboration

Zhao AH, Giardino A


 

ACS Chemical Biology

Exploring Methods of Targeting Histone Methyltransferases and Their Applications in Cancer Therapeutics

Wang MY, Liow P, Guzman MIT, Qi J


 

American Society of Clinical Oncology Educational Book

Overcoming KRAS-Mutant Lung Cancer

Luo J, Ostrem J


 

Annals of Surgical Oncology

Variation in Deescalated Axillary Surgical Practices in Older Women with Early-Stage Breast Cancer

Minami CA, Jin G, Schonberg MA, Freedman RA, King TA, Mittendorf EA


 

Bioorganic and Medicinal Chemistry Letters

Quinazolinones as Allosteric Fourth-Generation EGFR Inhibitors for the Treatment of NSCLC

Gero TW, Heppner DE, Beyett TS, To C, Azevedo SC, Jang J, Bunnell T, Feru F, Li Z, Hee Shin B, Gray NS, Jänne PA, Eck MJ, Scott DA


 

Blood Advances

Clonal Hematopoiesis is Associated with Increased Risk of Progression of Asymptomatic Waldenström Macroglobulinemia

Tahri S, Mouhieddine TH, Redd R, Lampe L, Nilsson KI, El-Khoury H, Su NK, Nassar AH, Adib E, Bindra G, Abou Alaiwi S, Trippa L, Steensma DP, Castillo JJ, Treon SP, Ghobrial IM, Sperling AS


 

Blood Advances

Genomic Profiling of a Randomized Trial of Interferon-? vs Hydroxyurea in MPN Reveals Mutation-Specific Responses

Stevenson K, Werner L, Duke W, Laurore C, Gibson CJ, Nag A, Thorner AR, Wollison B, Ellervik C, Neuberg DS, Lindsley RC, Mullally A


 

Blood Advances

M-CSF Secreting Leukemia Cell Vaccination for MDS/AML After Allogeneic HSCT: A Randomized, Double-Blinded, Phase 2 Trial

Ho VT, Kim HT, Brock J, Galinsky I, Daley H, Reynolds C, Weber A, Pozdnyakova O, Severgnini M, Nikiforow S, Cutler C, Koreth J, Antin JH, Gooptu M, Romee R, Shapiro R, Chen YB, Rosenblatt J, Avigan D, Hodi FS, Wu CJ, Ritz J, Soiffer RJ


 

Blood Cancer Journal

Identification and Validation of Ecto-5' Nucleotidase as an Immunotherapeutic Target in Multiple Myeloma

Ray A, Song Y, Du T, Buon L, Tai YT, Chauhan D, Anderson KC


 

Blood Cancer Journal

Validation of a Small Molecule Inhibitor of PDE6D-RAS Interaction with Favorable Anti-Leukemic Effects

Canovas Nunes S, De Vita S, McGuinness M, Duvert B, Harris C, Williams DA, Xu H


 

British Journal of Cancer

Combined PARP and HSP90 Inhibition: Preclinical and Phase 1 Evaluation in Patients with Advanced Solid Tumours

Konstantinopoulos PA, Cheng SC, Supko JG, Polak M, Bowes B, Sawyer H, Basada P, Hayes M, Curtis J, Horowitz N, Wright AA, Campos SM, Ivanova EV, Paweletz CP, Palakurthi S, Liu JF, D'Andrea AD, Gokhale PC, Chowdhury D, Matulonis UA, Shapiro GI


 

British Journal of Haematology

A British View on the Management of Waldenström Macroglobulinemia

Castillo JJ


 

British Journal of Haematology

Idelalisib Reduces Regulatory T Cells and Activates T Helper 17 Cell Differentiation in Relapsed Refractory Patients with Chronic Lymphocytic Leukaemia

Gadi D, Griffith A, Wang Z, Tyekucheva S, Rai V, Fernandes SM, Machado JH, Lederer J, Brown JR


 

Breast

Effect of Dose Reductions on Clinical Outcomes, or of Outcomes on Dose Reductions?

Regan MM


 

Breast Cancer Research and Treatment

Clinical Trial Data and Emerging Strategies: HER2-Positive Breast Cancer

Tolaney SM


 

Breast Cancer Research and Treatment

Gaps in Completion and Timeliness of Breast Surgery and Adjuvant Therapy: A Retrospective Cohort of Haitian Patients with Nonmetastatic Breast Cancer

Fadelu TA, Erfani P, Slater S, Triedman SA, Rebbeck TR


 

Breast Cancer Research and Treatment

Initiation and Tolerance of Chemoprevention Among Women with High-Risk Breast Lesions: The Potential of Low-Dose Tamoxifen

Bychkovsky B, Laws A, Katlin F, Hans M, Knust Graichen M, Pace LE, Scheib R, Garber JE, King TA


 

Cancer

"Is It Cancer or Not?" A Qualitative Exploration of Survivor Concerns Surrounding the Diagnosis and Treatment of Ductal Carcinoma in Situ

Rosenberg SM, Revette AC, Lowenstein CL, Frank ES, Partridge AH


 

Cancer Genetics

Vulvar Melanoma in Association with Germline MITF p.E318K Variant

Koeller DR, Schwartz A, DeSimone MS, Rana HQ, Rojas-Rudilla V, Russell-Goldman E, Laga AC, Lindeman NI, Garber JE, Ghazani AA


 

Cancer Immunology, Immunotherapy

Immune Cell Profiles in the Tumor Microenvironment of Early-Onset, Intermediate-Onset, and Later-Onset Colorectal Cancer

Ugai T, Väyrynen JP, Lau MC, Akimoto N, Väyrynen SA, Zhao M, Zhong R, Haruki K, Dias Costa A, Fujiyoshi K, Arima K, Wu K, Chan AT, Song M, Wang M, Lennerz JK, Ng K, Meyerhardt JA, Giannakis M, Nowak JA, Ogino S


 

Cancer Research

A Novel HER2-Selective Kinase Inhibitor Is Effective in HER2 Mutant and Amplified Non-Small Cell Lung Cancer

Son J, Jang J, Beyett TS, Eum Y, Haikala HM, Verano A, Lin M, Hatcher JM, Kwiatkowski NP, Eser Pö, Poitras MJ, Wang S, Xu M, Gokhale PC, Eck MJ, Jänne PA


 

Cancer Research

Functional Genomic Analysis of CDK4 and CDK6 Gene Dependency Across Human Cancer Cell Lines

Zhang Z, Golomb L, Meyerson M


 

Cell Reports Methods

BTBBCL6 Dimers as Building Blocks for Reversible Drug-Induced Protein Oligomerization

Yoon H, Burman SSR, Fischer ES, Slabicki M


 

Chemical Society Reviews

Small Molecule Modulation of Protein Polymerization

Fischer ES, Jones LH


 

Clinical Advances in Hematology and Oncology

Immunotherapy for Ovarian Cancer

Porter R, Matulonis UA


 

Clinical Cancer Research

Circulating Immune Cell and Outcome Analysis from the Phase 2 Study of PD-L1 Blockade with Durvalumab for Newly Diagnosed and Recurrent Glioblastoma

Nayak L, Dietrich J, Dunn GP, Flagg E, Gaffey S, Hayden J, Wen PY, Huang RY, Reardon DA


 

Clinical Cancer Research

Clinical Significance of PIK3CA and ESR1 Mutations in Circulating Tumor DNA: Analysis from the MONARCH 2 Study of Abemaciclib plus Fulvestrant

Tolaney SM


 

Clinical Cancer Research

Comparative Analysis and Isoform-Specific Therapeutic Vulnerabilities of KRAS Mutations in Non-Small Cell Lung Cancer

Ricciuti B, Son J, Okoro JJ, Eum Y, Wang X, Paranal R, Lin M, Haikala HM, Li J, Alessi JV, Chhoeu C, Redig AJ, Köhler J, Dholakia KH, Chen Y, Gokhale PC, Awad MM, Jänne PA, Ambrogio C


 

Clinical Cancer Research

Identification and Management of Pathogenic Variants in BRCA1, BRCA2, and PALB2 in a Tumor-Only Genomic Testing Program

Bychkovsky BL, Li T, Sotelo J, Tayob N, Gomy I, Chittenden A, Kane S, Stokes S, Hughes ME, Kim JS, Umeton R, Awad MM, Konstantinopoulos PA, Yurgelun MB, Wolpin BM, Taplin ME, Newmark RE, Johnson BE, Lindeman NI, MacConaill LE, Garber JE, Lin NU


 

Clinical Cancer Research

Microenvironment Is a Key Determinant of Immune Checkpoint Inhibitor Response

Cho SF, Anderson KC, Tai YT


 

Clinical Cancer Research

Phase 1b Clinical Trial with Alpelisib plus Olaparib for Patients with Advanced Triple-Negative Breast Cancer

Batalini F, Xiong N, Tayob N, Polak M, Shapiro GI, Adalsteinsson V, Winer EP, Konstantinopoulos PA, D'Andrea A, Matulonis UA, Wulf GM, Mayer EL


 

Clinical Cancer Research

Phase 1b/2 Study of Enzalutamide with Samotolisib (LY3023414) or Placebo in Patients with Metastatic Castration-Resistant Prostate Cancer

Sweeney CJ


 

Clinical Cancer Research

Phase II Study of Ponatinib in Advanced Gastrointestinal Stromal Tumors: Efficacy, Safety, and Impact of Liquid Biopsy and Other Biomarkers

George S, Fletcher JA


 

Clinical Cancer Research

Report of the First International Symposium on NUT Carcinoma

French CA, Cheng ML, Hanna GJ, DuBois SG, Liao S, Wu CJ, Polyak K, Shapiro GI


 

Clinical Cancer Research

Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Patients with NTRK Fusion-Positive Solid Tumors

Demetri GD, Lin JJ


 

Current Opinion in Endocrinology, Diabetes, and Obesity

Medical Management of Gastrointestinal Neuroendocrine Tumors

Perez K, Chan J


 

Current Opinion in Immunology

Editorial Overview: Vaccines: Reinvigorating Therapeutic Cancer Vaccines

Robles-Oteiza C, Wu CJ


 

Dermatologic Therapy

Topical Tofacitinib for the Management of Lymphocytic-Variant Hypereosinophilic Syndrome with Cutaneous Involvement

Said JT, Elman SA, Tawa M, Fisher DC, Merola JF, Kupper TS


 

Expert Review of Anticancer Therapy

Zanubrutinib for the Treatment of Adults with Waldenström Macroglobulinemia

Sarosiek S, Sermer D, Branagan AR, Treon SP, Castillo JJ


 

Genome Medicine

Variation in Targetable Genomic Alterations in Non-Small Cell Lung Cancer by Genetic Ancestry, Sex, Smoking History, and Histology

Adib E, Nassar AH, Abou Alaiwi S, Groha S, Akl EW, Sholl LM, Michael KS, Awad MM, Jänne PA, Gusev A, Kwiatkowski DJ


 

Gut

Pan-ERBB Kinase Inhibition Augments CDK4/6 Inhibitor Efficacy in Oesophageal Squamous Cell Carcinoma

Zhou J, Wu Z, Zhang Z, Goss L, McFarland J, Nagaraja A, Xie Y, Gu S, Peng K, Long H, Meyerson M, Bass A


 

Haematologica

Phase Ib Dose-Escalation Study of the Selective, Non-Covalent, Reversible Bruton's Tyrosine Kinase Inhibitor Vecabrutinib in B-Cell Malignancies

Davids MS, Brown JR


 

Journal of the American Society of Nephrology

Clonal Hematopoiesis and CKD Progression

Belizaire R


 

Journal of Dental Hygiene

A Review of Oral Chronic Graft-Versus-Host Disease: Considerations for Dental Hygiene Practice

Johnson LB, Oh U, Sroussi HY, Cintron K, Cutler CS, Treister NS


 

Journal of the National Comprehensive Cancer Network

Impact of Allocation on Survival During Intermittent Chemotherapy Shortages: A Modeling Analysis

Hantel A, McManus ML, Wadleigh M, Cotugno M, Abel GA


 

Journal of Neuro-Oncology

DICER1 Mutations in Primary Central Nervous System Tumors: New Insights into Histologies, Mutations, and Prognosis

Liu KX, Cacciotti C, Aizer AA, Rahman R, Malinowski S, Meredith DM, Kamihara J, Wen PY, Ligon KL, Chi SN, Marcus KJ, Yeo KK, Alexandrescu S, Haas-Kogan DA


 

Journal of Pain and Symptom Management

Clinical Decision Support for Symptom Management in Lung Cancer Patients: A Group RCT

Cooley ME, Mazzola E, Xiong N, Hong F, Braun IM, Halpenny B, Rabin MS, Abrahm JL


 

Journal of Pain and Symptom Management

Exploring the Feasibility of a Mindfulness-Music Therapy Intervention to Improve Anxiety and Stress in Adolescents and Young Adults with Cancer

Knoerl R, Mazzola E, Woods H, Buchbinder E, Frazier L, LaCasce A, Luskin MR, Phillips CS, Ligibel JA


 

Journal of Pain and Symptom Management

Normalization of Symptoms in Advanced Child Cancer: The PediQUEST-Response Case Study

Avery M, Feraco AM, Wolfe J, Dussel V


 

Journal of Virology

Global Increases in Human Immunodeficiency Virus Neutralization Sensitivity Due to Alterations in the Membrane-Proximal External Region of the Envelope Glycoprotein Can Be Minimized by Distant State 1-Stabilizing Changes

Wang Q, Esnault F, Zhao M, Nguyen HT, Sodroski JG


 

JCI Insight

Microbiota Dynamics in a Randomized Trial of Gut Decontamination During Allogeneic Hematopoietic Cell Transplantation

Li MM, Chen N, Duncan CN, Margossian SP, Lehmann LE, Birbrayer O, Silverstein S, Reynolds CG, Kim S, Ritz J, London WB, Whangbo JS


 

JCO Oncology Practice

Adjuvant Abemaciclib Plus Endocrine Therapy in the Treatment of High-Risk Early Breast Cancer: ASCO Guideline Rapid Recommendation Update Q and A

Freedman RA


 

JCO Oncology Practice

Oncology Fellows' Clinical Discussions, Perceived Knowledge, and Formal Training Regarding Medical Cannabis Use: A National Survey Study

Patell R, Bindal P, Dodge L, Elavalakanar P, Freed JA, Rangachari D, Buss M, Schonberg M, Braun I


 

Leukemia

Antibody and T-Cell Responses to SARS-CoV-2 Vaccination in Myeloproliferative Neoplasm Patients

How J, Gallagher KME, Liu Y, Katsis K, Elder EL, Larson RC, Leick MB, Neuberg D, Maus MV, Hobbs GS


 

Leukemia

Cell-Free DNA for the Detection of Emerging Treatment Failure in Relapsed/Refractory Multiple Myeloma

Waldschmidt JM, Yee AJ, Vijaykumar T, Pinto RA, Frede J, Anand P, Bianchi G, Guo G, Potdar S, Seifer C, Nair MS, Kokkalis A, Kloeber JA, Shapiro S, Budano L, Mann M, O'Donnell EK, Zhang CZ, Laubach JP, Munshi NC, Richardson PG, Anderson KC, Raje NS, Knoechel B, Lohr JG


 

Leukemia

Combination Therapy Targeting Erk1/2 and CDK4/6i in Relapsed Refractory Multiple Myeloma

Adamia S, Bhatt S, Wen K, Chyra Z, Fell GG, Tai YT, Pioso MS, Letai A, Dorfman DM, Hideshima T, Anderson KC


 

Leukemia

Inhibition of the Deubiquitinating Enzyme USP47 as a Novel Targeted Therapy for Hematologic Malignancies Expressing Mutant EZH2

Yang J, Weisberg EL, Ni W, Meng C, Zhang S, Magin RS, Doherty L, Buhrlage SJ, Griffin JD


 

Leukemia

JAK3 Mutations and Mitochondrial Apoptosis Resistance in T-Cell Acute Lymphoblastic Leukemia

Bodaar K, Yamagata N, Barthe A, Landrigan J, Chonghaile TN, Burns M, Stevenson KE, Silverman LB, Letai A, Gutierrez A


 

Nature Cancer

An Allosteric Inhibitor Against the Therapy-Resistant Mutant Forms of EGFR in Non-Small Cell Lung Cancer

To C, Beyett TS, Jang J, Feng WW, Bahcall M, Haikala HM, Shin BH, Heppner DE, Rana JK, Leeper BA, Soroko KM, Poitras MJ, Gokhale PC, Kobayashi Y, Kurppa KJ, Gero TW, Ogino A, Mushajiang M, Xu C, Zhang Y, Scott DA, Eck MJ, Gray NS, Jänne PA


 

Nature Reviews Clinical Oncology

Single-Cell Profiling of Tumour Evolution in Multiple Myeloma - Opportunities for Precision Medicine

Dutta AK, Alberge JB, Sklavenitis-Pistofidis R, Lightbody ED, Getz G, Ghobrial IM


 

Nature Reviews Drug Discovery

Kinase Drug Discovery 20 Years After Imatinib

Jänne PA


 

Neuro-Oncology

Upfront Molecular Targeted Therapy for the Treatment of BRAF-Mutant Pediatric High-Grade Glioma

Rosenberg T, Yeo KK, Alexandrescu S, Prabhu SP, Tsai JW, Malinowski S, Wright KD, Chi SN


 

Neuro-Oncology Practice

Frequency, Etiologies, Risk Factors, and Sequelae of Falls Among Patients with Brain Metastases: A Population- and Institutional-Level Analysis

Lamba N, Cao F, Cagney DN, Catalano PJ, Haas-Kogan DA, Wen PY, Aizer AA


 

NPJ Breast Cancer

PARP Inhibition in Breast Cancer: Progress Made and Future Hopes

Tung N, Garber JE


 

Oncologist

Cetuximab and Irinotecan with or without Bevacizumab in Refractory Metastatic Colorectal Cancer: BOND-3, an ACCRU Network Randomized Clinical Trial

Lipsyc-Sharf M, Yurgelun MB, Rubinson DA, Schrag D, Meyerhardt JA, Ng K


 

Oncologist

Surrogacy Beyond Prognosis: The Importance of "Trial-Level" Surrogacy

Regan MM, Sweeney CS


 

Palliative Medicine

"I Think that She Would Have Wanted. . .": Qualitative Interviews with Bereaved Caregivers Reveal Complexity in Measuring Goal-Concordant Care at the End of Life

Durieux BN, Berrier A, Gray TF, Lakin JR, Cunningham R, Morris SE, Tulsky JA, Sanders JJ


 

Pediatric Blood and Cancer

Ocular Abnormalities at Diagnosis and After the Completion of Treatment in Children and Adolescents with Newly Diagnosed Acute Lymphoblastic Leukemia

Gotti G, Stevenson K, Blonquist TM, Mantagos JS, Silverman LB, Place AE


 

Pediatric Blood and Cancer

"Per Protocol" Practice Patterns for Children's Oncology Group Trials within the Radiation Oncology Community

Liu KX, Hammoudeh L, Haas-Kogan DA


 

PLoS One

Serological Testing for SARS-CoV-2 Antibodies of Employees Shows Low Transmission Working in a Cancer Center

Meyerhardt JA, Yue H, Nowak RP, Brais L, Ma C, Johnson S, Harrod J, Burman SSR, Hendrickson LM, Fischinger S, Alter G, Hahn W, Johnson BE, Fischer ES


 

PLoS Pathogen

Long-Read Sequencing Reveals Complex Patterns of Wraparound Transcription in Polyomaviruses

Nomburg J, Frost TC, Datta C, Vasudevan S, Meyerson M, DeCaprio JA


 

Prostate

Implementation of a Prostate Cancer-Specific Targeted Sequencing Panel for Credentialing of Patient-Derived Cell Lines and Genomic Characterization of Patient Samples

Stover EH, Oh C, Keskula P, Choudhury AD, Tseng YY, Adalsteinsson VA, Lohr JG, Thorner AR, Ducar M, Kryukov GV, Rosenberg M, Freeman SS, Zhang Z, Wu X, Van Allen EM, Loda M, Wu CL, Taplin ME, Boehm JS


 

Radiology

Importance of 68Ga-FAPI PET/CT for Detection of Cancer

Jacobson FL, Van den Abbeele AD


 

Radiotherapy and Oncology

Major Adverse Cardiac Event Risk Prediction Model Incorporating Baseline Cardiac Disease, Hypertension, and Logarithmic Left Anterior Descending Coronary Artery Radiation Dose in Lung Cancer (CHyLL)

Tjong MC, Bitterman DS, Brantley K, Nohria A, Hoffmann U, Atkins KM, Mak RH


 

Science Advances

Mendelian Randomization Supports Bidirectional Causality Between Telomere Length and Clonal Hematopoiesis of Indeterminate Potential

Nakao T, Bick AG, Uddin MM, Niroula A, Honigberg MC, Pampana A, Gibson CJ, Griffin GK, Bhattacharya R, DeMeo DL, Qiao D, Cho MH, Redline S, Weiss ST, Manson JE, Silverman EK, Libby P, Ellinor PT, Ebert BL, Natarajan P


 

Small Methods

A Robust Method for Perfusable Microvascular Network Formation In Vitro

Wan Z, Shelton SE, Lorch JH, Barbie DA


 

Therapeutic Advances in Hematology

An Overview of Treatment Options for Patients with Relapsed/Refractory Multiple Myeloma and Renal Impairment

Richardson PG


 

Transplant and Cell Therapy

Hepatitis B Virus Vaccination After Allogeneic Hematopoietic Cell Transplantation Prevents Post-Transplant HBV Reactivation

Hammond SP, Ho VT, Marty FM