Welcome to Dana-Farber's Research News
January 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
FLT(3)-ing About: The Search for the Best Inhibitor
Stone RM
In this issue of Blood, Loo et al report results from the fourth prospective randomized trial of a putative fms-like tyrosine kinase 3 (FLT3) inhibitor (in this case sorafenib) vs placebo plus chemotherapy in fit adults with newly diagnosed mutant FLT3 internal tandem duplication (ITD) acute myeloid leukemia (AML). Unlike the CALGB 10603/RATIFY and the QUANTUM-FIRST trials, which showed that midostaurin and quizartinib, respectively, produced superior survival compared with placebo plus chemotherapy, the current Australian trial was viewed as negative; neither survival nor event survival was better for patients randomized to sorafenib. The hope that sorafenib, a multikinase inhibitor approved in renal carcinoma because of its vascular endothelial growth factor- inhibiting activity, would be useful in the AML setting was based in part on its activity with chemotherapy in induction and superiority to placebo after allogenic transplant, each in the mutant FLT3 ITD context. Further trials of sorafenib plus chemotherapy in genetically unrestricted AML suggested some benefit, but toxicity was significant in older adults.
Blood
Miller PG, Sperling AS, Mayerhofer C, McConkey ME, Ellegast JM, Da Silva C, Cohen DN, Sharda A, Yan N, Saha S, Schluter C, Schechter I, S?abicki M, Sandoval B, Kahn J, Gibson CJ, Scadden DT, Stegmaier K, Lindsley RC, Ebert BL
PPM1D encodes a phosphatase that is recurrently activated across cancer, most notably in therapy-related myeloid neoplasms. However, the function of PPM1D in hematopoiesis and its contribution to tumor cell growth remain incompletely understood. Using conditional mouse models, we uncover a central role for Ppm1d in hematopoiesis and validate its potential as a therapeutic target. We find that Ppm1d regulates the competitive fitness and self-renewal of hematopoietic stem cells (HSCs) with and without exogenous genotoxic stresses. We also show that although Ppm1d activation confers cellular resistance to cytotoxic therapy, it does so to a lesser degree than p53 loss, informing the clonal competition phenotypes often observed in human studies. Notably, loss of Ppm1d sensitizes leukemias to cytotoxic therapies in vitro and in vivo, even in the absence of a Ppm1d mutation. Vulnerability to PPM1D inhibition is observed across many cancer types and dependent on p53 activity. Importantly, organism-wide loss of Ppm1d in adult mice is well tolerated, supporting the tolerability of pharmacologically targeting PPM1D. Our data link PPM1D gain-of-function mutations to the clonal expansion of HSCs, inform human genetic observations, and support the therapeutic targeting of PPM1D in cancer.
Cancer Discovery
Formate Supplementation Enhances Antitumor CD8+ T-cell Fitness and Efficacy of PD-1 Blockade
Rowe JH, Elia I, Shahid O, Gaudiano EF, Sifnugel NE, Johnson S, Reynolds AG, Fung ME, Joshi S, LaFleur MW, Park JS, Pauken KE, Freeman GJ, Haigis MC, Sharpe AH
The tumor microenvironment (TME) restricts antitumor CD8+ T-cell function and immunotherapy responses. Cancer cells compromise the metabolic fitness of CD8+ T cells within the TME, but the mechanisms are largely unknown. Here we demonstrate that one-carbon (1C) metabolism is enhanced in T cells in an antigen-specific manner. Therapeutic supplementation of 1C metabolism using formate enhances CD8+ T-cell fitness and antitumor efficacy of PD-1 blockade in B16-OVA tumors. Formate supplementation drives transcriptional alterations in CD8+ T-cell metabolism and increases gene signatures for cellular proliferation and activation. Combined formate and anti-PD-1 therapy increases tumor-infiltrating CD8+ T cells, which are essential for enhanced tumor control. Our data demonstrate that formate provides metabolic support to CD8+ T cells reinvigorated by anti-PD-1 to overcome a metabolic vulnerability in 1C metabolism in the TME to further improve T-cell function.
SIGNIFICANCE: This study identifies that deficiencies in 1C metabolism limit the efficacy of PD-1 blockade in B16-OVA tumors. Supplementing 1C metabolism with formate during anti-PD-1 therapy enhances CD8+ T-cell fitness in the TME and CD8+ T-cell-mediated tumor clearance. These findings demonstrate that formate supplementation can enhance exhausted CD8+ T-cell function. See related commentary by Lin et al., p. 2507. This article is featured in Selected Articles from This Issue, p. 2489.
Cancer Discovery
Ultrasensitive Detection of Circulating LINE-1 ORF1p as a Specific Multicancer Biomarker
Taylor MS, Wu C, Zhang SJ, Senussi Y, Cajuso T, Cheng WC, Heaps JD, Miller BD, Mori K, Cohen L, Bhan I, Franses JW, Yang X, Taplin ME, Wang X, Christiani DC, Johnson BE, Meyerson M, Uppaluri R, Egloff AM, Denault EN, Spring LM, Arora KS, Yilmaz OH, Cohen S, Sharova T, Chi G, Norden BL, Song Y, Nieman LT, Pappas L, Parikh AR, Strickland MR, Corcoran RB, Matulonis UA, Chan AT, Skates SJ, Rueda BR, Klempner SJ, Deshpande V, Ting DT
Improved biomarkers are needed for early cancer detection, risk stratification, treatment selection, and monitoring treatment response. Although proteins can be useful blood-based biomarkers, many have limited sensitivity or specificity for these applications. Long INterspersed Element-1 (LINE-1) open reading frame 1 protein (ORF1p) is a transposable element protein overexpressed in carcinomas and high-risk precursors during carcinogenesis with negligible expression in normal tissues, suggesting ORF1p could be a highly specific cancer biomarker. To explore ORF1p as a blood-based biomarker, we engineered ultrasensitive digital immunoassays that detect mid-attomolar (10-17 mol/L) ORF1p concentrations in plasma across multiple cancers with high specificity. Plasma ORF1p shows promise for early detection of ovarian cancer, improves diagnostic performance in a multianalyte panel, provides early therapeutic response monitoring in gastroesophageal cancers, and is prognostic for overall survival in gastroesophageal and colorectal cancers. Together, these observations nominate ORF1p as a multicancer biomarker with potential utility for disease detection and monitoring.
SIGNIFICANCE: The LINE-1 ORF1p transposon protein is pervasively expressed in many cancers and is a highly specific biomarker of multiple common, lethal carcinomas and their high-risk precursors in tissue and blood. Ultrasensitive ORF1p assays from as little as 25 ?L plasma are novel, rapid, cost-effective tools in cancer detection and monitoring. See related commentary by Doucet and Cristofari, p. 2502. This article is featured in Selected Articles from This Issue, p. 2489.
Journal of Clinical Oncology
ASCO Ethical Guidance for the Practical Management of Oncology Drug Shortages
Hantel A, Moy B, Rosenberg AR, Marron JM, Peppercorn J
In early 2023, national shortages of generic chemotherapies used to treat many common cancers forced many hospitals and clinics to allocate drugs in scarcity. Shortages of chemotherapies such as cisplatin and carboplatin are an acute example of an ongoing problem, with professional societies, media, policy-makers, regulators, and the Biden administration calling for action and relief. Shortages that affect patients with cancer are not unique to antineoplastic therapies; they have also been subject to clinically significant shortages of pressors, benzodiazepines, and antibiotics, among others. Given the complexity of the problem and the long timeline toward solutions addressing supply chain, demand, and manufacturing challenges, chemotherapy shortages are likely to continue into the foreseeable future. Patients and oncologists will be faced with delays, waitlists, or suboptimal clinical options and outcomes.
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
Jänne PA
PURPOSE: Patritumab deruxtecan, or HER3-DXd, is an antibody-drug conjugate consisting of a fully human monoclonal antibody to human epidermal growth factor receptor 3 (HER3) attached to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. We assessed the efficacy and safety of HER3-DXd in patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC).
METHODS: This phase II study (ClinicalTrials.gov identifier: NCT04619004) was designed to evaluate HER3-DXd in patients with advanced EGFR-mutated NSCLC previously treated with EGFR tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy (PBC). Patients received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks or an uptitration regimen (3.2 ? 4.8 ? 6.4 mg/kg). The primary end point was confirmed objective response rate (ORR; RECIST 1.1) by blinded independent central review (BICR), with a null hypothesis of 26.4% on the basis of historical data.
RESULTS: Enrollment into the uptitration arm closed early on the basis of a prespecified benefit-risk assessment of data from the phase I U31402-A-U102 trial. In total, 225 patients received HER3-DXd 5.6 mg/kg once every 3 weeks. As of May 18, 2023, median study duration was 18.9 (range, 14.9-27.5) months. Confirmed ORR by BICR was 29.8% (95% CI, 23.9 to 36.2); median duration of response, 6.4 months; median progression-free survival, 5.5 months; and median overall survival, 11.9 months. The subgroup of patients with previous osimertinib and PBC had similar outcomes. Efficacy was observed across a broad range of pretreatment tumor HER3 membrane expression levels and across diverse mechanisms of EGFR TKI resistance. In patients with nonirradiated brain
metastases at baseline (n = 30), the confirmed CNS ORR by BICR per CNS RECIST was 33.3% (95% CI, 17.3 to 52.8). The safety profile (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) was manageable and tolerable, consistent with previous observations.
CONCLUSION: After tumor progression with EGFR TKI therapy and PBC in patients with EGFR-mutated NSCLC, HER3-DXd once every 3 weeks demonstrated clinically meaningful efficacy with durable responses, including in CNS metastases. A phase III trial in EGFR-mutated NSCLC after progression on an EGFR TKI is ongoing (HERTHENA-Lung02; ClinicalTrials.gov identifier: NCT05338970).
Journal of Clinical Oncology
Germline EGFR Mutations and Familial Lung Cancer
Oxnard GR, Chen R, Pharr JC, Koeller DR, Bertram AA, Dahlberg SE, Rainville I, Sholl LM, Jänne PA, Garber JE
PURPOSE: The genomic underpinnings of inherited lung cancer risk are poorly understood. This prospective study characterized the clinical phenotype of patients and families with germline EGFR pathogenic variants (PVs).
METHODS: The Investigating Hereditary Risk from T790M study (ClinicalTrials.gov identifier: NCT01754025) enrolled patients with lung cancer whose tumor profiling harbored possible germline EGFR PVs and their relatives, either in person or remotely, providing germline testing and follow-up.
RESULTS: A total of 141 participants were enrolled over a 5-year period, 100 (71%) remotely. Based upon previous genotyping, 116 participants from 59 kindreds were tested for EGFR T790M, demonstrating a pattern of Mendelian inheritance with variable lung cancer penetrance. In confirmed or obligate carriers of a germline EGFR PV from 39 different kindreds, 50/91 (55%) were affected with lung cancer with 34/65 (52%) diagnosed by age 60 years. Somatic testing of lung cancers in carriers revealed that 35 of 37 (95%) had an EGFR driver comutation. Among 36 germline carriers without a cancer diagnosis, 15 had computed tomography (CT) imaging and nine had lung nodules, including a 28-year-old with >10 lung nodules. Given geographic enrichment of germline EGFR T790M in the southeast United States, genome-wide haplotyping of 46 germline carriers was performed and identified a 4.1-Mb haplotype shared by 41 (89%), estimated to originate 223-279 years ago.
CONCLUSION: To our knowledge, this is the first prospective description of familial EGFR-mutant lung cancer, identifying a recent founder germline EGFR T790M variant enriched in the Southeast United States. The high prevalence of EGFR-driver lung adenocarcinomas and lung nodules in germline carriers supports effort to identify affected patients and family members for investigation of CT-based screening for these high-risk individuals.
Journal of the National Cancer Institute
El Zarif T, Freeman D, Choueiri TK
BACKGROUND: Treatment options for penile squamous cell carcinoma are limited. We sought to investigate clinical outcomes and safety profiles of patients with penile squamous cell carcinoma receiving immune checkpoint inhibitors.
METHODS: This retrospective study included patients with locally advanced or metastatic penile squamous cell carcinoma receiving immune checkpoint inhibitors between 2015 and 2022 across 24 centers in the United States, Europe, and Asia. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. Objective response rates were determined per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events, version 5.0. Two-sided statistical tests were used for comparisons.
RESULTS: Among 92 patients, 8 (8.7%) were Asian, 6 (6.5%) were Black, and 24 (29%) were Hispanic and/or Latinx. Median (interquartile range) age was 62 (53-70) years. In all, 83 (90%) had metastatic penile squamous cell carcinoma, and 74 (80%) had received at least second-line treatment. Most patients received pembrolizumab monotherapy (n?=?26 [28%]), combination nivolumab-ipilimumab with or without multitargeted tyrosine kinase inhibitors (n?=?23 [25%]), or nivolumab (n?=?16 [17%]) or cemiplimab (n?=?15 [16%]) monotherapies. Median overall and progression-free survival were 9.8 months (95% confidence interval?=?7.7 to 12.8 months) and 3.2 months (95% confidence interval?=?2.5 to 4.2 months), respectively. The objective response rate was 13% (n?=?11/85) in the overall cohort and 35% (n?=?7/20) in patients with lymph node-only metastases. Visceral metastases, Eastern Cooperative Oncology Group (ECOG) performance status of 1 or higher, and a higher neutrophil/lymphocyte ratio were associated with worse overall survival. Treatment-related adverse events occurred in 27 (29%) patients, and 9.8% (n?=?9) of the events were grade 3 or higher.
CONCLUSIONS: Immune checkpoint inhibitors are active in a subset of patients with penile squamous cell carcinoma. Future translational studies are warranted to identify patients more likely to derive clinical benefit from immune checkpoint inhibitors.
Nature Cell Biology
Metabolically Regulated Lineages in Prostate Cancer
Bakht MK, Beltran H
Lineage plasticity and epigenetic changes underlie prostate development and cancer evolution. A new study shows that basal and luminal prostate cells have distinct metabolic profiles, with a basal-to-luminal shift intensifying pyruvate oxidation. Metabolic changes in turn influence chromatin architecture, lineage reprogramming and treatment sensitivity.
Nature Chemical Biology
Targeting ROS Production Through Inhibition of NADPH Oxidases
Reis J, Gorgulla C, Törner R, Cox H 3rd, Viennet T, Yang MH, Ronan MM, Rees MG, Roth JA, Arthanari H
NADPH oxidases (NOXs) are transmembrane enzymes that are devoted to the production of reactive oxygen species (ROS). In cancers, dysregulation of NOX enzymes affects ROS production, leading to redox unbalance and tumor progression. Consequently, NOXs are a drug target for cancer therapeutics, although current therapies have off-target effects: there is a need for isoenzyme-selective inhibitors. Here, we describe fully validated human NOX inhibitors, obtained from an in silico screen, targeting the active site of Cylindrospermum stagnale NOX5 (csNOX5). The hits are validated by in vitro and in cellulo enzymatic and binding assays, and their binding modes to the dehydrogenase domain of csNOX5 studied via high-resolution crystal structures. A high-throughput screen in a panel of cancer cells shows activity in selected cancer cell lines and synergistic effects with KRAS modulators. Our work lays the foundation for the development of inhibitor-based methods for controlling the tightly regulated and highly localized ROS sources.
Nature Communications
Author Correction: Comprehensive Genomic Characterization of HER2-Low and HER2-0 Breast Cancer
Tarantino P, Gupta H, Hughes ME, Files J, Strauss S, Kirkner G, Feeney AM, Li Y, Garrido-Castro AC, Bychkovsky BL, DiLascio S, Sholl L, MacConaill L, Lindeman N, Johnson BE, Meyerson M, Jeselsohn R, Qiu X, Li R, Long H, Dillon D, Cherniack AD, Tolaney SM, Lin NU
In this article, the author names Paolo Tarantino, Hersh Gupta, Melissa E. Hughes, Janet Files, Sarah Strauss, Gregory Kirkner, Anne-Marie Feeney, Yvonne Li, Ana C. Garrido-Castro, Romualdo Barroso-Sousa, Brittany L. Bychkovsky, Simona DiLascio, Lynette Sholl, Laura MacConaill, Neal Lindeman, Bruce E. Johnson, Matthew Meyerson, Rinath Jeselsohn, Xintao Qiu, Rong Li, Henry Long, Eric P. Winer, Deborah Dillon, Giuseppe Curigliano, Andrew D. Cherniack, Sara M. Tolaney & Nancy U. Lin were incorrectly written as P. Tarantino, H. Gupta, M. E. Hughes, J. Files, S. Strauss, G. Kirkner, A.-M. Feeney, Y. Li, A. C. Garrido-Castro, R. Barroso-Sousa, B. L. Bychkovsky, S. DiLascio, L. Sholl, L. MacConaill, N. Lindeman, B. E. Johnson, M. Meyerson, R. Jeselsohn, X. Qiu, R. Li, H. Long, E. P. Winer, D. Dillon, G. Curigliano, A. D. Cherniack, S. M. Tolaney & N. U. Lin. The original article has been corrected.
Nature Communications
Role of PDGFRA(+) Cells and a CD55(+) PDGFRA(Lo) Fraction in the Gastric Mesenchymal Niche
Manieri E, Tie G, Seruggia D, Madha S, Maglieri A, Fujiwara Y, Zhang K, Orkin SH, He R, McCarthy N, Shivdasani RA
PDGFRA-expressing mesenchyme supports intestinal stem cells. Stomach epithelia have related niche dependencies, but their enabling mesenchymal cell populations are unknown, in part because previous studies pooled the gastric antrum and corpus. Our high-resolution imaging, transcriptional profiling, and organoid assays identify regional subpopulations and supportive capacities of purified mouse corpus and antral PDGFRA+ cells. Sub-epithelial PDGFRAHi myofibroblasts are principal sources of BMP ligands and two molecularly distinct pools distribute asymmetrically along antral glands but together fail to support epithelial growth in vitro. In contrast, PDGFRALo CD55+ cells strategically positioned beneath gastric glands promote epithelial expansion in the absence of other cells or factors. This population encompasses a small fraction expressing the BMP antagonist Grem1. Although Grem1+ cell ablation in vivo impairs intestinal stem cells, gastric stem cells are spared, implying that CD55+ cell activity in epithelial self-renewal derives from other subpopulations. Our findings shed light on spatial, molecular, and functional organization of gastric mesenchyme and the spectrum of signaling sources for epithelial support.
Proceedings of the National Academy of Science of the U.S.A.
Peripheral Blood TCR Clonotype Diversity as an Age-Associated Marker of Breast Cancer Progression
Nishida J, Cristea S, Bodapati S, Puleo J, Bai G, Patel A, Hughes M, Snow C, Collins LC, Feeney AM, Slowik K, Bossuyt V, Dillon D, Lin NU, Partridge AH, Michor F, Polyak K
Immune escape is a prerequisite for tumor growth. We previously described a decline in intratumor activated cytotoxic T cells and T cell receptor (TCR) clonotype diversity in invasive breast carcinomas compared to ductal carcinoma in situ (DCIS), implying a central role of decreasing T cell responses in tumor progression. To determine potential associations between peripheral immunity and breast tumor progression, here, we assessed the peripheral blood TCR clonotype of 485 breast cancer patients diagnosed with either DCIS or de novo stage IV disease at younger (<45) or older (?45) age. TCR clonotype diversity was significantly lower in older compared to younger breast cancer patients regardless of tumor stage at diagnosis. In the younger age group, TCR-? clonotype diversity was lower in patients diagnosed with de novo stage IV breast cancer compared to those diagnosed with DCIS. In the older age group, DCIS patients with higher TCR-? clonotype diversity were more likely to have a recurrence compared to those with lower diversity. Whole blood transcriptome profiles were distinct depending on the TCR-? Chao1 diversity score. There were more CD8+ T cells and a more active immune environment in DCIS tumors of young patients with higher peripheral blood TCR-? Chao1 diversity than in those with lower diversity. These results provide insights into the role that host immunity plays in breast cancer development across different age groups.
American Journal of Transplantation
Guinan EC, Contreras-Ruiz L, Crisalli K, Rickert C, Rosales I, Makar R, Colvin R, Turka LA, Markmann JF
Annals of Internal Medicine
Kelkar AH, Cliff ERS, Jacobson CA, Abel GA, Redd R, Hunink MGM, Cutler C
Annals of Surgical Oncology
Distribution and Rate of Myxoid Liposarcoma Spine Metastases: Impact on Surveillance Imaging
Vierra BM, Saadat LV, Hornick JL, Jagannathan JP, Ferrone ML, Wagner AJ, Wang J, Baldini EH, Raut C, Fairweather M
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
Annals of Surgical Oncology
Kantor O, King TA, Jones A, Glass C, Leonard SJ, Ogayo ER, Mayer EL, Freedman RA, Mittendorf EA
Biomolecular NMR Assignments
Matosin S, Fischer PD, Droemer MA, Tavares I, Ficarro SB, Arthanari H
Biostatistics
Wu X, Dominici F, Braun D
Blood Advances
Lane AA, Garcia JS, Raulston EG, Garzon JLN, Galinsky I, Baxter EW, Leonard R, DeAngelo DJ, Luskin MR, Reilly CR, Stahl M, Stone RM, Vedula RS, Wadleigh M, Winer ES, Stevenson KE, Neuberg DS, Ren S, Keating JH
Blood Advances
Romee R, Koreth J
Blood Cancer Journal
Dutta D, Liu J, Wen K, Kurata K, Fulciniti M, Gulla A, Hideshima T, Anderson KC
BMJ Supportive and Palliative Care
A Tool for Guiding Goal-Concordant Medical Recommendations in Paediatric Serious Illness
Porter AS, Freitas JE, Frechette EM, Wolfe J, Snaman JM
Bone Marrow Transplantation
Gray TF, Amonoo HL
British Journal of Haematology
Ryan CE, Zon RL, Redd R, Fisher DC, Crombie JL, Sadrzadeh H, Kim AI, Nayak L, Chukwueke UN, Jacobson CA, Frigault MJ, Armand P, Merryman RW
Breast
Tolaney SM
Cancer
Diller LR, Park JR, Rosenberg AR, Shusterman S, Mack JW
Cancer Research
All Roads Lead to Rome: YAP/TAZ Activity Influences Efficacy of KRASG12C Inhibitors
Johnson CW, Haigis KM
Cancer Research
Myeloid Cells Pave the Metastatic Road in Breast Cancer
Michaud DE, Guerriero JL
Cell Reports
Heterogeneity and Transcriptional Drivers of Triple-Negative Breast Cancer
Jovanovi? B, Temko D, Stevens LE, Seehawer M, Fassl A, Murphy K, Anand J, Garza K, Gulvady A, Qiu X, Harper NW, Daniels VW, Xiao-Yun H, Ge JY, Ale?kovi? M, Pyrdol J, Hinohara K, Egri SB, Papanastasiou M, Vadhi R, Font-Tello A, Witwicki R, Peluffo G, Trinh A, Shu S, Diciaccio B, Ekram MB, Subedee A, Herbert ZT, Wucherpfennig KW, Letai AG, Jaffe JD, Sicinski P, Brown M, Dillon D, Long HW, Michor F, Polyak K
Cell Reports Medicine
Li Y, Mahadevan NR, Duplaquet L, Hong D, Durmaz YT, Jones KL, Cho H, Morrow M, Protti A, Poitras MJ, Springer BF, Bronson RT, Southard J, Thai T, Li S, Lizotte PH, Gokhale PC, Nguyen QD, Oser MG
Clinical Cancer Research
Huffman BM, Feng H, Parmar K, Wang J, Kapner KS, Kochupurakkal B, Martignetti DB, Sadatrezaei G, Abrams TA, Biller LH, Giannakis M, Ng K, Patel AK, Perez KJ, Singh H, Rubinson DA, Schlechter BL, Andrews E, Hannigan AM, Dunwell S, Getchell Z, Raghavan S, Wolpin BM, D'Andrea AD, Aguirre AJ, Shapiro GI, Cleary JM
Clinical Cancer Research
Yang E, London W, Chi S, Bandopadhayay P
Clinical Cancer Research
Overcoming Resistance in Chronic Lymphocytic Leukemia - Maybe Less is More?
Davids MS
Clinical Trials
Onyeaka H, Weber DB, Amonoo HL
Current Neurology and Neuroscience Reports
Advances in Treatment of Diffuse Midline Gliomas
Wright KD
Current Opinion in Nephrology and Hypertension
Onconephrology: Mitigation of Renal Injury in Chemotherapy Administration
Selamet U
Current Opinion in Neurology
Novel Trial Designs in Neuro-Oncology
Wen PY
Drugs
Waldenström Macroglobulinemia: Targeted Agents Taking Center Stage
Sarosiek S, Castillo JJ
EMBO Reports
Tetracyclines Activate Mitoribosome Quality Control and Reduce ER Stress to Promote Cell Survival
Ronayne CT, Jackson TD, Bennett CF, Perry EA, Kantorovic N, Puigserver P
Future Oncology
Brown JR
Genes and Development
Mendez-Dorantes C, Burns KH
Gut Microbes
The Microbiome and Rise of Early-Onset Cancers: Knowledge Gaps and Research Opportunities
Ugai T, Ogino S
Haematologica
Crombie JL, Jacobson CA, Redd R, Saucier A, Armand P
Hematological Oncology
LaCasce A
Hematology/Oncology Clinics of North America
CAR T Cells: Past Successes, Current Limitations, and Future Opportunities
Jacobson CA
Hematology/Oncology Clinics of North America
Jacobson CA
Hematology/Oncology Clinics of North America
Chimeric Antigen Receptor T Cells in Multiple Myeloma
Shah P, Sperling AS
International Journal of Radiation Oncology, Biology, Physics
Liu KX, PJ, Gallotto SL, Marcus KJ, Haas-Kogan DA, Tarbell NJ, MacDonald SM, Yock TI
JAMA Network Open
Well-Being Parameters and Intention to Leave Current Institution Among Academic Physicians
Ligibel JA
Journal of the American Chemical Society
Gibson WJ, Sadagopan A, Shoba VM, Choudhary A, Meyerson M, Schreiber SL
Journal of the American College of Surgeons
Jin Q, Waks AG, Spring LM, Wrabel E, Tayob N, King TA, Metzger-Filho O
Journal of Healthcare Risk Management
Schaffer AC, Tishler RB, Jacobson JO
Journal for ImmunoTherapy of Cancer
Wolpin BM, Dias Costa A, Lenehan P, Cardot-Ruffino V, Rodig S, Pfaff K, Dougan SK, Nowak JA, Rahma O
Journal of the National Comprehensive Cancer Network
What Constitutes Quality of Life? Perspectives of Adolescents and Young Adults with Advanced Cancer
Hinkle J, Fisher L, Lakin JR, Lefebvre A, Wall CB, Mack JW
Journal of Pain and Symptom Management
Rosenberg AR
Journal of Psychosocial Oncology
Knoerl R, Sannes TS, Giobbie-Hurder A, Frank ES, Ligibel JA
Journal of Thoracic Oncology
Genotype Versus Phenotype: Defining Predictive Biomarkers of Immunotherapy Responsev
Makarem M, Rotow JK
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
Manz CR
Lancet Haematology
Is There a Path Forward for Immunotherapy in Patients with Myelodysplastic Syndromes?
Stahl M
Leukemia and Lymphoma
Localized Upper Extremity Edema Secondary to Bruton's Tyrosine Kinase Inhibition
Leung BW, Fay CJ, Said JT, Sheets AR, Lian CG, Brown JR, Castillo JJ, Sarosiek S, Flynn C, LeBoeuf NR
Molecular Therapy Methods and Clinical Development
Poletti V, Montepeloso A, Pellin D, Biffi A
Nature Reviews Cancer
Approaching Cancer During Pregnancy
Varella L, Partridge AH
Nature Reviews Cancer
Targeting Cancer Cell Dormancy
Agudo J
Neuro-Oncology
Insulin Feedback is a Targetable Resistance Mechanism of PI3K Inhibition in Glioblastoma
Wen PY, Ligon KL, Cantley LC
Neuro-Oncology
Cooney T, Warren KE
Oncologist
The 5th Kidney Cancer Research Summit: Research Accelerating Cures for Renal Cell Carcinoma in 2023
Choueiri TK, Pels K
Oral Oncology
Batool S, Sethi RKV, Wang A, Dabekaussen K, Egloff AM, Uppaluri R, Shin J, Rettig EM
Otolaryngology-Head and Neck Surgery
Personal Social Networks and Care-Seeking for Head and Neck Cancer: A Qualitative Study
Batool S, Hansen EE, Sethi RKV, Rettig EM, Goguen LA, Annino D, Uppaluri R, Faden DL, Dohan D, Dhand A, Reich AJ, Bergmark RW
PEC Innovation
Testing the What Matters to Me Workbook in a Diverse Sample of Seriously Ill Patients and Caregivers
Fromme EK, Mendoza K
Pediatric Blood and Cancer
Campbell K, Posner A, Chen N, Cavanaugh K, Bhushan K, Janeway KA, Shulman DS, George S, Klega K, Crompton B, London WB, DuBois SG
Preventive Medicine Reports
Nagler E, Sorensen G
Prostate
Ravi P, Kwak L, Xie W, Chipidza F, Yang X, Bubley G, Kaplan I, Kibel AS, Nguyen P, Taplin ME
Substance Use and Misuse
Onyeaka HK, Daskalakis E, Deary EC, Boardman AC, Amonoo HL
Transplantation and Cellular Therapy
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