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Dana-Farber Research Publication 10.1.2021

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October 1, 2021

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. 

 
 

Cancer Cell

Seong BKA, Dharia NV, Lin S, Donovan KA, Robichaud A, Conway A, Hamze A, Ross L, Alexe G, Adane B, Nabet B, Ferguson FM, Stolte B, Wang EJ, Sun J, Piccioni F, Gray NS, Fischer ES, Stegmaier K

Fusion-transcription factors (fusion-TFs) represent a class of driver oncoproteins that are difficult to therapeutically target. Recently, protein degradation has emerged as a strategy to target these challenging oncoproteins. The mechanisms that regulate fusion-TF stability, however, are generally unknown. Using CRISPR-Cas9 screening, we discovered tripartite motif-containing 8 (TRIM8) as an E3 ubiquitin ligase that ubiquitinates and degrades EWS/FLI, a driver fusion-TF in Ewing sarcoma. Moreover, we identified TRIM8 as a selective dependency in Ewing sarcoma compared with >700 other cancer cell lines. Mechanistically, TRIM8 knockout led to an increase in EWS/FLI protein levels that was not tolerated. EWS/FLI acts as a neomorphic substrate for TRIM8, defining the selective nature of the dependency. Our results demonstrate that fusion-TF protein stability is tightly regulated and highlight fusion oncoprotein-specific regulators as selective therapeutic targets. This study provides a tractable strategy to therapeutically exploit oncogene overdose in Ewing sarcoma and potentially other fusion-TF-driven cancers.
 

 

Cancer Cell

Wang Y, Manokaran C, Wu S, Roberts TM

Cyclin-dependent kinase 7 (CDK7) is implicated in regulating the expression of cancer-dependent genes, and multiple CDK7-targeted therapies are currently under clinical investigation. Three recent studies elucidate the structure of human transcription machinery, offering vital mechanistic insights into CDK7 function and a potential pharmacodynamic marker of CDK7 activity in tumors.
 

 

Cancer Discovery

Malone CF, Dharia NV, Kugener G, Forman AB, Rothberg MV, Abdusamad M, Gonzalez A, Kuljanin M, Robichaud AL, Conway AS, Dempster JM, Paolella BR, Dumont N, Hovestadt V, Mancias JD,
Younger ST, Root DE, Golub TR, Vazquez F, Stegmaier K

Cancer dependency maps, which use CRISPR/Cas9 depletion screens to profile the landscape of genetic dependencies in hundreds of cancer cell lines, have identified context-specific dependencies that could be therapeutically exploited. An ideal therapy is both lethal and precise, but these depletion screens cannot readily distinguish between gene effects that are cytostatic or cytotoxic. Here, we use a diverse panel of functional genomic screening assays to identify NXT1 as a selective and rapidly lethal in vivo relevant genetic dependency in MYCN-amplified neuroblastoma. NXT1 heterodimerizes with NXF1, and together they form the principal mRNA nuclear export machinery. We describe a previously unrecognized mechanism of synthetic lethality between NXT1 and its paralog NXT2: their common essential binding partner NXF1 is lost only in the absence of both. We propose a potential therapeutic strategy for tumor-selective elimination of a protein that, if targeted directly, is expected to cause widespread toxicity. SIGNIFICANCE: We provide a framework for identifying new therapeutic targets from functional genomic screens. We nominate NXT1 as a selective lethal target in neuroblastoma and propose a therapeutic approach where the essential protein NXF1 can be selectively eliminated in tumor cells by exploiting the NXT1-NXT2 paralog relationship. See related commentary by Wang and Abdel-Wahab, p. 2129.This article is highlighted in the In This Issue feature, p. 2113.
 

 

Gastroenterology

Singh H, Hornick JL, Madha S, Cejas P, Jajoo K, Singh P, Shivdasani RA

BACKGROUND & AIMS: Tissue metaplasia is uncommon in adults because established cis-element programs resist rewiring. In Barrett's esophagus, the distal esophageal mucosa acquires a predominantly intestinal character, with notable gastric features, and is predisposed to developing invasive cancers. We sought to understand the chromatin underpinnings of Barrett's metaplasia and why it commonly displays simultaneous gastric and intestinal properties.

METHODS: We profiled cis-regulatory elements with active histone modifications in primary human biopsy materials using chromatin immunoprecipitation followed by DNA sequencing. Mutations in Barrett's esophagus were examined in relation to tissue-specific enhancer landscapes using a random forest machine-learning algorithm. We also profiled open chromatin at single-cell resolution in primary Barrett's biopsy specimens using the assay for transposase-accessible chromatin. We used 1- and 2-color immunohistochemistry to examine protein expression of tissue-restricted genes.

RESULTS: Barrett's esophagus bears epigenome fingerprints of human stomach and intestinal columnar, but not esophageal squamous, epithelia. Mutational patterns were best explained as arising on the epigenome background of active gastric cis-elements, supporting the view that adjoining stomach epithelium is a likely tissue source. Individual cells in Barrett's metaplasia coexpress gastric and intestinal genes, reflecting concomitant chromatin access at enhancers ordinarily restricted to one or the other epithelium. Protein expression of stomach-specific mucins; CLDN18; and a novel gastric marker, ANXA10, showed extensive tissue and subclonal heterogeneity of dual stomach-intestinal cell states.

CONCLUSIONS: These findings reveal mixed and dynamic tissue-restricted chromatin states and phenotypic heterogeneity in Barrett's esophagus. Pervasive intragland variation argues against stem-cell governance of this phenotype.
 

 

JAMA Oncology

Sella T, Weiss A, Mittendorf EA, King TA, Metzger-Filho O

IMPORTANCE: In clinical practice, neoadjuvant endocrine therapy (NET) is rarely used despite being an effective treatment modality able to downstage tumors and facilitate breast-conserving surgery.

OBSERVATIONS: Using data from studies conducted since 2000, we provide readers with a critical in-depth review on clinical aspects related to the application of NET in the treatment of hormone receptor (HR)-positive/ERBB2 (formerly HER2)-negative breast cancer. This includes an overview of patient-selection criteria, regimen choice, treatment duration, evaluation of response by imaging, interpretation of pathology after treatment, and surgical considerations. Areas of controversy include the use of gene-expression tests for patient selection, treatment of premenopausal women, surgical management of the axilla after NET, and adjuvant systemic therapy decision-making, including the use of chemotherapy.

CONCLUSIONS AND RELEVANCE: NET is an optimal treatment modality for a considerable proportion of postmenopausal women diagnosed with HR-positive tumors. The treatment landscape for HR-positive breast cancer is evolving, with novel agents and the growing use of gene expression profiling to define treatment selection. As such, it is likely that NET use will increase and the practical considerations outlined here will become more important.
 

 

Journal of Clinical Oncology

Yang DD, Nguyen PL, D'Amico AV

The benefit of elective pelvic lymph node (LN) radiation in node-negative prostate cancer is controversial. As such, we applaud Murthy et al on successfully undertaking the POP-RT randomized trial. The authors demonstrated that for a cohort of men with node-negative disease and an estimated nodal risk ? 20% (by the Roach formula), pelvic LN radiation significantly improved the primary end point of 5-year biochemical failure-free survival (BFFS; 95.0% v 81.2%) and, on exploratory analysis, was associated with improved distant metastasis-free survival (5-year DMFS 95.9% v 89.2%).
 

 

Journal of Clinical Oncology

Tewari AK, Gillessen S, Sweeney CJ

Virgo et al have provided the updated ASCO guidelines for the initial management of noncastrate advanced, recurrent, or metastatic prostate cancer, which we greatly appreciated. We would like to propose some refinements to treatment recommendations based on timing of metastatic presentation and disease burden.
 

 

Journal of Clinical Oncology

D'Amico AV, Xie W, McMahon E, Loffredo M, Medeiros S, Bubley G

PURPOSE: Although docetaxel is not recommended when managing men with unfavorable-risk prostate cancer (PC) given negative or inconclusive results from previous randomized trials, unstudied benefits may exist.

METHODS: Between September 21, 2005, and January 13, 2015, we randomly assigned 350 men 1:1 with T1c-4N0M0 unfavorable-risk PC to receive radiation therapy (RT) and androgen deprivation therapy (ADT) plus docetaxel (60 mg/m2 once every 3 weeks for three cycles before RT and 20 mg/m2 once weekly during RT) versus ADT + RT. We evaluated the treatment effect of adding docetaxel to ADT + RT on the primary end point of overall survival (OS) and the incidence of RT-induced cancers and explored whether the impact of the treatment effect on OS differed within prostate-specific antigen (PSA) subgroups (< 4, > 20 v 4-20 ng/mL) using the interaction test for heterogeneity adjusted for age and PC prognostic factors.

RESULTS: After a median follow-up of 10.2 years, 89 men died (25.43%); of these, 42 from PC (47.19%). Although OS was not significantly increased in the docetaxel arm (the restricted mean survival time over 10 years was 9.11 v 8.82 years; P = .22), significantly fewer RT-induced cancers were observed (10-year estimates: 0.61% v 4.90%; age-adjusted hazard ratio of 0.13; 95% CI, 0.02 to 0.97; P = .046). The treatment effect of adding docetaxel to ADT + RT on OS significantly differed in men with a PSA < 4 ng/mL versus 4-20 ng/mL (adjusted hazard ratio: 0.27 and 1.51, respectively) because of less PC-specific mortality on the docetaxel arm (0.00% v 28.57%) among men with PSA < 4 ng/mL.

CONCLUSION: Adding docetaxel to ADT + RT did not prolong OS in men with

unfavorable-risk PC, but decreased RT-induced cancer incidence, and may prolong OS in the subgroup of men with a PSA < 4 ng/mL by reducing PC-specific mortality.
 

 

Journal of Clinical Oncology

Tolaney SM, Partridge AH, Winer EP, Krop IE

In a letter to the editor in response to our article in Journal of Clinical Oncology, Tanaka et al2 bring up several important points. The first concern they raise is the use of a single-arm study design to evaluate invasive disease-free survival (iDFS) with trastuzumab emtansine (T-DM1). While we recognize that ideally a prospective, randomized trial would be conducted, we felt that such a design would not have been feasible if powered to compare efficacy between the two arms. Given the low event rate seen with anti–human epidermal growth factor receptor 2 (HER2) therapy for stage I HER2-positive breast cancer, a randomized trial would require a minimum of several thousands of patients to detect a difference in outcomes. The ATEMPT trial was not designed to replace paclitaxel plus trastuzumab (TH) as the standard of care, but to establish a second treatment option. Our goal was to determine whether treatment with T-DM1 would result in a clinically acceptable iDFS with a 3-year failure rate of 5% or less. Additionally, we sought to compare clinically relevant toxicities (CRTs) between T-DM1 and TH. The trial demonstrated a 3-year iDFS of 97.8%, with just two distant events, and the overall rates of CRTs were similar across the two arms. This trial is not able to conclude that T-DM1 is better than no treatment, nor that treatment with T-DM1 is better than, or equivalent to, treatment with TH. However, given the outstanding efficacy seen with T-DM1, and important patient-reported outcomes suggesting significantly lower rates of neuropathy, better work productivity, and less alopecia, T-DM1 may be considered an alternative treatment option to TH for patients with stage I HER2-positive disease.
 

 

Journal of Clinical Oncology

Enzinger AC, Keating NL, Cutler DM, Landrum MB, Wright AA

PURPOSE: Heightened regulations have decreased opioid prescribing across the United States, yet little is known about trends in opioid ccess among patients dying of cancer.

METHODS: Among 270,632 Medicare fee-for-service decedents with poor prognosis cancers, we used part D data to examine trends from 2007 to 2017 in opioid prescription fills and opioid potency (morphine milligram equivalents per day [MMED]) near the end-of-life (EOL), defined as the 30 days before death or hospice enrollment. We used administrative claims to evaluate trends in pain-related emergency department (ED) visits near EOL.

RESULTS: Between 2007 and 2017, the proportion of decedents with poor prognosis cancers receiving ‚â• 1 opioid prescription near EOL declined 15.5% (relative percent difference [RPD]), from 42.0% (95% CI, 41.4 to 42.7) to 35.5% (95% CI, 34.9 to 36.0) and the proportion receiving  1 long-acting opioid prescription declined 36.5% (RPD), from 18.1% (95% CI, 17.6 to 18.6) to 11.5% (95% CI, 11.1 to 11.9). Among decedents receiving opioids near EOL, the mean daily dose fell 24.5%, from 85.6 MMED (95% CI, 82.9 to 88.3) to 64.6 (95% CI, 62.7 to 66.6) MMED. Overall, the total amount of opioids prescribed per decedent near EOL (averaged across those who did and did not receive an opioid) fell 38.0%, from 1,075 morphine milligram equivalents per decedent (95% CI, 1,042 to 1,109) to 666 morphine milligram equivalents per decedent (95% CI, 646 to 686). Simultaneously, the proportion of patients with pain-related ED visits increased 50.8% (RPD), from 13.2% (95% CI, 12.7 to 13.6) to 19.9% (95% CI, 19.4 to 20.4). Sensitivity analyses demonstrated similar declines in opioid utilization in the 60 and 90 days before death or hospice, and suggested that trends in opioid access were not confounded by secular trends in hospice utilization.

CONCLUSION: Opioid use among patients dying of cancer has declined substantially from 2007 to 2017. Rising pain-related ED visits suggests that EOL cancer pain management may be worsening.
 

 

Journal of the National Cancer Institute

Yuan C, Morales-Oyarvide V, Perez K, Tabung FK, Kraft P, Sesso HD, Giovannucci EL, Manson JE, Stampfer MJ, Ng K, Wolpin BM, Babic A

BACKGROUND: Chronic inflammation may promote initiation and progression of pancreatic cancer, but no studies have examined the association between inflammation in the period before diagnosis and pancreatic cancer survival.

METHODS: We prospectively examined the association of prediagnostic plasma levels of C-reactive protein, interleukin-6, and tumor necrosis factor-a receptor 2 with survival among 492 participants from 5 large US prospective cohort studies who developed pancreatic cancer. Using an empirical dietary inflammatory pattern (EDIP) score, we evaluated whether long-term proinflammatory diets were associated with survival among 1153 patients from 2 of the 5 cohorts. Cox proportional hazards regression was used to estimate hazard ratios for death with adjustment for potential confounders. All statistical tests were 2-sided.

RESULTS: Higher prediagnostic levels of C-reactive protein, interleukin-6, and tumor necrosis factor-a receptor 2 were individually associated with reduced survival (Ptrend = .03, .01, and .04, respectively). Compared with patients with a combined inflammatory biomarker score of 0 (all 3 marker levels below medians), those with a score of 3 (all 3 marker levels above medians) had a hazard ratio for death of 1.57 (95% confidence interval = 1.16 to 2.12; Ptrend = .003), corresponding to median overall survival times of 8 vs 5 months. Patients consuming the most proinflammatory diets (EDIP quartile 4) in the prediagnostic period had a hazard ratio for death of 1.34 (95% confidence interval = 1.13 to 1.59; Ptrend = .01), compared with those consuming the least proinflammatory diets (EDIP quartile 1).

CONCLUSION: Prediagnostic levels of inflammatory biomarkers and long-term proinflammatory diets were inversely associated with pancreatic cancer survival.
 

 

Molecular Cell

Mulvaney KM, Blomquist C, Acharya N, Li R, Ranaghan MJ, O'Keefe M, Rodriguez DJ, Young MJ, Kesar D, Pal D, Jain SS, Mullin-Bernstein Z, Columbus J, Bozal FK, Skepner A, Raymond D,
LaRussa S, McKinney DC, Freyzon Y, Baidi Y, Porter D, Aguirre AJ, Ianari A, McMillan B, Sellers WR

PRMT5 is an essential arginine methyltransferase and a therapeutic target in MTAP-null cancers. PRMT5 uses adaptor proteins for substrate recruitment through a previously undefined mechanism. Here, we identify an evolutionarily conserved peptide sequence shared among the three known substrate adaptors (CLNS1A, RIOK1, and COPR5) and show that it is necessary and sufficient for interaction with PRMT5. We demonstrate that PRMT5 uses modular adaptor proteins containing a common binding motif for substrate recruitment, comparable with other enzyme classes such as kinases and E3 ligases. We structurally resolve the interface with PRMT5 and show via genetic perturbation that it is required for methylation of adaptor-recruited substrates including the spliceosome, histones, and ribosomal complexes. Furthermore, disruption of this site affects Sm spliceosome activity, leading to intron retention. Genetic disruption of the PRMT5-substrate adaptor interface impairs growth of MTAP-null tumor cells and is thus a site for development of therapeutic inhibitors of PRMT5.
 

 

Molecular Cell

Hunkeler M, Jin CY, Ma MW, Overwijn D, Fischer ES

HECT ubiquitin ligases play essential roles in metazoan development and physiology. The HECT ligase HUWE1 is central to the cellular stress response by mediating degradation of key death or survival factors, including Mcl1, p53, DDIT4, and Myc. Although mutations in HUWE1 and related HECT ligases are widely implicated in human disease, our molecular understanding remains limited. Here we present a comprehensive investigation of full-length HUWE1, deepening our understanding of this class of enzymes. The N-terminal ∼3,900 amino acids of HUWE1 are indispensable for proper ligase function, and our cryo-EM structures of HUWE1 offer a complete molecular picture of this large HECT ubiquitin ligase. HUWE1 forms an alpha solenoid-shaped assembly with a central pore decorated with protein interaction modules. Structures of HUWE1 variants linked to neurodevelopmental disorders as well as of HUWE1 bound to a model substrate link the functions of this essential enzyme to its three-dimensional organization.
 

 

Nature

Slavik KM, Morehouse BR, Ragucci AE, Zhou W, Lee ASY, Kranzusch PJ

Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that produces the second messenger cG[2'-5']pA[3'-5']p (2'3'-cGAMP) and controls activation of innate immunity in mammalian cells1-5. Animal genomes typically encode multiple proteins with predicted homology to cGAS6-10, but the function of these uncharacterized enzymes is unknown. Here we show that cGAS-like receptors (cGLRs) are innate immune sensors that are capable of recognizing divergent molecular patterns and catalysing synthesis of distinct nucleotide second messenger signals. Crystal structures of human and insect cGLRs reveal a nucleotidyltransferase signalling core shared with cGAS and a diversified primary ligand-binding surface modified with notable insertions and deletions. We demonstrate that surface remodelling of cGLRs enables altered ligand specificity and used a forward biochemical screen to identify cGLR1 as a double-stranded RNA sensor in the model organism Drosophila melanogaster. We show that RNA recognition activates Drosophila cGLR1 to synthesize the novel product cG[3'-5']pA[2'-5']p (3'2'-cGAMP). A crystal structure of Drosophila stimulator of interferon genes (dSTING) in complex with 3'2'-cGAMP explains selective isomer recognition, and 3'2'-cGAMP induces an enhanced antiviral state in vivo that protects from viral infection. Similar to radiation of Toll-like receptors in pathogen immunity, our results establish cGLRs as a diverse family of metazoan pattern recognition receptors.
 

 

Nature Immunology

Raundhal M, Ghosh S, Myers SA, Cuoco MS, Singer M, Carr SA, Waikar SS, Bonventre JV, Ritz J, Stone RM, Steensma DP, Regev A, Glimcher LH

Patients with myelodysplastic syndromes (MDSs) display severe anemia but the mechanisms underlying this phenotype are incompletely understood. Right open-reading-frame kinase 2 (RIOK2) encodes a protein kinase located at 5q15, a region frequently lost in patients with MDS del(5q). Here we show that hematopoietic cell-specific haploinsufficient deletion of Riok2 (Riok2f/+Vav1cre) led to reduced erythroid precursor frequency leading to anemia. Proteomic analysis of Riok2f/+Vav1cre erythroid precursors suggested immune system activation, and transcriptomic analysis revealed an increase in p53-dependent interleukin (IL)-22 in Riok2f/+Vav1cre CD4+ T cells (TH22). Further, we discovered that the IL-22 receptor, IL-22RA1, was unexpectedly present on erythroid precursors. Blockade of IL-22 signaling alleviated anemia not only in Riok2f/+Vav1cre mice but also in wild-type mice. Serum concentrations of IL-22 were increased in the subset of patients with del(5q) MDS as well as patients with anemia secondary to chronic kidney disease. This work reveals a possible therapeutic opportunity for reversing many stress-induced anemias by targeting IL-22 signaling.
 

 

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

Gonzalez-Del Pino GL, Li K, Park E, Schmoker AM, Ha BH, Eck MJ

The RAF/MEK/ERK pathway is central to the control of cell physiology, and its dysregulation is associated with many cancers. Accordingly, the proteins constituting this pathway, including MEK1/2 (MEK), have been subject to intense drug discovery and development efforts. Allosteric MEK inhibitors (MEKi) exert complex effects on RAF/MEK/ERK pathway signaling and are employed clinically in combination with BRAF inhibitors in malignant melanoma. Although mechanisms and structures of MEKi bound to MEK have been described for many of these compounds, recent studies suggest that RAF/MEK complexes, rather than free MEK, should be evaluated as the target of MEKi. Here, we describe structural and biochemical studies of eight structurally diverse, clinical-stage MEKi to better understand their mechanism of action on BRAF/MEK complexes. We find that all of these agents bind in the MEK allosteric site in BRAF/MEK complexes, in which they stabilize the MEK activation loop in a conformation that is resistant to BRAF-mediated dual phosphorylation required for full activation of MEK. We also show that allosteric MEK inhibitors act most potently on BRAF/MEK complexes rather than on free active MEK, further supporting the notion that a BRAF/MEK complex is the physiologically relevant pharmacologic target for this class of compounds. Our findings provide a conceptual and structural framework for rational development of RAF-selective MEK inhibitors as an avenue to more effective and better-tolerated agents targeting this pathway.
 

 

Science Translational Medicine

Eser Pö, Paranal RM, Son J, Ivanova E, Kuang Y, Haikala HM, To C, Okoro JJ, Dholakia KH, Choi J, Eum Y, Ogino A, Missios P, Ercan D, Xu M, Poitras MJ, Wang S, Ngo K, Dills M, Yanagita M, Lopez T, Lin M, Tsai J, Chambers ES, Heng J, Santucci AD, Michael K, Oxnard GR, Barbie DA, Sholl LM, Bahcall M, Palakurthi S, Gokhale PC, Paweletz CP, Daley GQ, Jänne PA

The clinical efficacy of epidermal growth factor receptor (EGFR)–targeted therapy in EGFR-mutant non–small cell lung cancer is limited by the development of drug resistance. One mechanism of EGFR inhibitor resistance occurs through amplification of the human growth factor receptor (MET) proto-oncogene, which bypasses EGFR to reactivate downstream signaling. Tumors exhibiting concurrent EGFR mutation and MET amplification are historically thought to be codependent on the activation of both oncogenes. Hence, patients whose tumors harbor both alterations are commonly treated with a combination of EGFR and MET tyrosine kinase inhibitors (TKIs). Here, we identify and characterize six patient-derived models of EGFR-mutant, MET-amplified lung cancer that have switched oncogene dependence to rely exclusively on MET activation for survival. We demonstrate in this MET-driven subset of EGFR TKI-refractory cancers that canonical EGFR downstream signaling was governed by MET, even in the presence of sustained mutant EGFR expression and activation. In these models, combined EGFR and MET inhibition did not result in greater efficacy in vitro or in vivo compared to single-agent MET inhibition. We further identified a reduced EGFR:MET mRNA expression stoichiometry as associated with MET oncogene dependence and single-agent MET TKI sensitivity. Tumors from 10 of 11 EGFR inhibitor–resistant EGFR-mutant, MET-amplified patients also exhibited a reduced EGFR:MET mRNA ratio. Our findings reveal that a subset of EGFR-mutant, MET-amplified lung cancers develop dependence on MET activation alone, suggesting that such patients could be treated with a single-agent MET TKI rather than the current standard-of-care EGFR and MET inhibitor combination regimens.
 

 

Abdominal Radiology

Shinagare AB, Gujrathi I, Cochon L, Burk KS, Khorasani R
 

 

American Journal of Clinical Oncology

Remolano MC, Schlossman J, Harrison B, Yeh E, Jacene H, Nakhlis F, Block C, Rosenbluth JM, Garrido-Castro AC, Overmoyer BA
 

 
 

 

Annals of Nuclear Medicine

Karls S, Kravets S, Wang Y, Cheng S, Perez K, Chan J, Jacene H
 

 

Annals of Surgery Open

Lam MB, Riley K, Mehtsun W, Phelan J, Orav EJ, Burke LG
 

 

Annals of Surgical Oncology

Kantor O, Means J, Grossmith S, Dey T, Bellon JR, Mittendorf EA, King TA
 

 

Annals of Surgical Oncology

Kantor O, Means J, Grossmith S, Dey T, Bellon JR, Mittendorf EA, King TA
 

 
 

 

Blood Advances

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

 
 

 

Blood Advances

Crombie JL, Redd RA, Saucier A, Jacobson CA, Armand P 
 

 
 

 

Bone Marrow Transplantation

Amonoo HL, El-Jawahri A, Celano CM, Harnedy LE, Longley RM, Onyeaka HK, Healy BC, Cutler CS, Pirl WF, Huffman JC
 

 
 

 

Breast Cancer Research and Treatment

Balch SM, Vaz-Luis I, Li T, Tayob N, Jain E, Helvie K, Buendia-Buendia JE, Shannon E, Isakoff SJ, Tung NM, Krop IE, Lin NU, Wagle N, Freedman RA
 

 
 

 
 

 
 

 
 

 

Cancer Research

Gomez Tejeda Zanudo J, Mao P, Kowalski K, Johnson GN, Letai A, Montero J, Wagle N
 

 
 

 
 

 

Cell Reports

Tewari AK, Cheung ATM, Crowdis J, Conway JR, Camp SY, Wankowicz SA, Livitz DG, Park J, Lis RT, Bosma-Moody A, He MX, AlDubayan SH, Zhang Z, Leshchiner I, Brown M, Balk SP, Getz G,
Taplin ME, Van Allen EM
 

 
 

 

Clinical Cancer Research

Do KT, Kochupurakkal B, Kelland S, de Jonge A, Hedglin J, Powers A, Quinn N, Gannon C, Vuong L, Parmar K, Lazaro JB, D'Andrea AD, Shapiro GI
 

 

Clinical Cancer Research

Waldschmidt JM, Anand P, Frede J, Kokkalis A, Dimitrova V, Potdar S, Nair MS, Vijaykumar T, Im NG, Guillaumet-Adkins A, Stuart H, Budano L, Sotudeh N, Guo G, Grassberger C, Yee AJ, Laubach JP, Richardson PG, Anderson KC, Raje NS, Knoechel B, Lohr JG
 

 

Developmental Cell

Tasdemir-Yilmaz OE, Druckenbrod NR, Olukoya OO, Dong W, Yung AR, Bastille I, Pazyra-Murphy MF, Sitko AA, Hale EB, Vigneau S, Gimelbrant AA, Kharchenko PV, Goodrich LV, Segal RA
 

 
 

 
 

 

European Urology

Berchuck JE, Silver R, Kwak L, Xie W, Lee GM, Freedman ML, Kibel AS, Van Allen EM, Taplin ME
 

 
 

 
 

 
 

 
 

 
 

 

Gynecologic Oncology

Krasner CN, Campos SM, Young CL, Chadda KR, Lee H, Horowitz NS, Konstantinopoulos PA, D'Ascanio AM, Matulonis UA, Penson RT
 

 

International Journal of Environmental Research and Public Health

Nagler EM, Stelson EA, Karapanos M, Burke L, Wallace LM, Peters SE, Sorensen G
 

 

International Journal of Radiation Oncology, Biology, Physics

Bellon JR, Chen YH, Rees R, Taghian AG, Wong JS, Punglia RS, Shiloh RY, Warren LEG,
Krishnan MS, Phillips J, Pretz J, Jimenez R, Macausland S, Pashtan I, Andrews C, Isakoff SJ,
Winer EP, Tolaney SM
 

 
 

 

JAMA Surgery

Dominici L, Hu J, Zheng Y, Kim HJ, King TA, Peppercorn J, Come SE, Wong JS, Partridge AH, Rosenberg SM
 

 

Journal of Cancer Education

Tsai FD, Stuver S, Stern R, Winkler M, Vallurupalli M, Luskin MR, Braun D, Parent A, Kilbridge KL
 

 

Journal of Cancer Survivorship

Knoerl R, Giobbie-Hurder A, Berfield J, Meyerhardt JA, Wright AA, Ligibel JA
 

 
 

 
 

 
 

 

Journal of Pain and Symptom Management

Chen JJ, Roldan CS, Nichipor AN, Balboni TA, Krishnan MS, Revette AC, Hertan LM 
 

 

Journal of Pain and Symptom Management

Goldhirsch J, Halpenny B, Scott N, Ma Y, Rodriguez MS, Abrahm JL
 

 

Journal of Sexual Medicine

Bober SL, Chevalier LL
 

 

Journal of Thoracic Imaging

Nishino M, Lu J, Hino T, Vokes NI, Jänne PA, Hatabu H, Johnson BE
 

 
 

 

Leukemia

Merryman RW, Ho VT, Frigault MJ, Chen YB, Joyce RM, Rahimian M, Armand P
 

 
 

 
 

 

Leukemia Research

Aleissa MM, Alshehri BS, Gonzalez-Bocco IH, McDonnell AM, Leblebjian H, Marty FM, Luskin MR
 

 
 

 

Neuro-Oncology

Driver J, Hoffman SE, Tavakol S, Woodward E, Maury EA, Bhave V, Aizer AA, Alexander BM, Ligon KL, Reardon DA, Wen PY, Al-Mefty O, Ligon AH, Dubuc AM, Beroukhim R, Claus EB, Santagata S, Bi WL
 

 

Neuro-Oncology

Lamba N, Wen PY, Aizer AA
 

 

Neuro-Oncology

Aquilanti E, Kageler L, Wen PY, Meyerson M
 

 

NPJ Biofilms and Microbiomes

Movassagh M, Bebell LM, Roberts DJ, Irizarry RA
 

 
 

 
 

 

Oncologist

Barroso-Sousa R, Vaz-Luis I, Di Meglio A, Hu J, Li T, Rees R, Sinclair N, Milisits L, Leone JP, Constantine M, Faggen M, Briccetti F, Block C, Partridge A, Burstein H, Waks AG, Tayob N, Trippa L, Tolaney SM, Hassett MJ, Winer EP, Lin NU
 

 
 

 
 

 

Pediatric Blood and Cancer

Zheng DJ, Umaretiya PJ, Schwartz ER, Al-Sayegh H, Ma C, Muriel AC, Bona K
 

 

Pediatric Blood and Cancer

Greenzang KA, Kelly CA, Al-Sayegh H, Mack JW
 

 

Pediatric Critical Care Medicine

Moynihan KM, Purol N, Alexander PMA, Wolfe J
 

 

Practical Radiation Oncology

Chen YH, Venkatachalam V, Alban GM, Buscariollo DL, Cheng T, King MT, Pretz JL, Russo AL, Lee LJ
 

 

Practical Radiation Oncology

Atkins KM, Bitterman DS, Chaunzwa TL, Williams CL, Rahman R, Kozono DE, Baldini EH, Aerts HJWL, Hoffmann U, Nohria A, Mak RH
 

 

Prostate Cancer and Prostatic Diseases

Berchuck JE, Beltran H 
 

 
 

 

Radiologic Clinics of North America

Hughes NM, Jacene HA
 

 

Supportive Care in Cancer

Dee EC, Nipp RD, Muralidhar V, Yu Z, Butler SS, Nguyen PL
 

 

Transplantation and Cellular Therapy

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