Welcome to Dana-Farber's Research News
January 1, 2023
This twice-monthly newsletter highlights the research endeavors at Dana-Farber Cancer Institute, noting recently published papers available from PubMed where Dana-Farber faculty are listed as first or senior authors. If you are a Dana-Farber faculty member and you think your paper is missing from Research News, please let us know at: Michael_buller@dfci.harvard.edu.
Cancer Discovery
BAF Complex Maintains Glioma Stem Cells in Pediatric H3K27M Glioma
Panditharatna E, Marques JG, Wang T, Trissal MC, Liu I, Jiang L, Groves A, Dharia NV, Li D, Hoffman SE, Kugener G, Shaw ML, Mire HM, Hack OA, Dempster JM, Lareau C, Dai L, Sigua LH, Wyatt M, Kalani Z, Goodale A, Vazquez F, Piccioni F, Doench JG, Root DE, Anastas JN, Jones KL, Conway AS, Stopka S, Regan MS, Liang Y, Seo HS, Song K, Bashyal P, Jerome WP, Mathewson ND, Dhe-Paganon S, Suv?† ML, Nguyen QD, Ligon KL, Shi Y, Agnihotri S, Agar NYR, Stegmaier K, Stiles CD, Golub TR, Qi J, Filbin MG
Diffuse midline gliomas are uniformly fatal pediatric central nervous system cancers that are refractory to standard-of-care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape. To interrogate for epigenetic dependencies, we performed a CRISPR screen and show that patient-derived H3K27M-glioma neurospheres are dependent on core components of the mammalian BAF (SWI/SNF) chromatin remodeling complex. The BAF complex maintains glioma stem cells in a cycling, oligodendrocyte precursor cell-like state, in which genetic perturbation of the BAF catalytic subunit SMARCA4 (BRG1), as well as pharmacologic suppression, opposes proliferation, promotes progression of differentiation along the astrocytic lineage, and improves overall survival of patient-derived xenograft models. In summary, we demonstrate that therapeutic inhibition of the BAF complex has translational potential for children with H3K27M gliomas.
SIGNIFICANCE: Epigenetic dysregulation is at the core of H3K27M-glioma tumorigenesis. Here, we identify the BRG1-BAF complex as a critical regulator of enhancer and transcription factor landscapes, which maintain H3K27M glioma in their progenitor state, precluding glial differentiation, and establish pharmacologic targeting of the BAF complex as a novel treatment strategy for pediatric H3K27M glioma. See related commentary by Beytagh and Weiss, p. 2730. See related article by Mo et al., p. 2906.
Cancer Discovery
Dutta AK, Alberge JB, Lightbody ED, Boehner CJ, Dunford A, Sklavenitis-Pistofidis R, Cowan AN, Su NK, Horowitz EM, Barr H, Hevenor L, Beckwith JB, Perry J, Cao A, Lin Z, Nadeem O, Stewart C, Getz G, Ghobrial IM
Multiple Myeloma (MM) develops from well-defined precursor stages, however, invasive bone marrow (BM) biopsy limits screening and monitoring strategies for patients. We enumerated circulating tumor cells (CTCs) from 261 patients (84 MGUS, 155 SMM, and 22 MM), with neoplastic cells detected in 84%. We developed a novel approach, MinimuMM-seq, which enables detection of translocations and copy number abnormalities through whole-genome sequencing of highly pure CTCs. Application to CTCs in a cohort of 51 patients, 24 with paired BM, was able to detect 100% of clinically reported BM biopsy events and could replace molecular cytogenetics for diagnostic yield and risk classification. Longitudinal sampling of CTCs in 8 patients revealed major clones could be tracked in the blood, with clonal evolution and shifting dynamics of subclones over time. Our findings provide proof of concept that CTC detection and genomic profiling could be used clinically for monitoring and managing disease in MM.
Cancer Discovery
Mutant NPM1 Directly Regulates Oncogenic Transcription in Acute Myeloid Leukemia
Uckelmann HJ, Haarer EL, Takeda R, Hatton C, Marinaccio C, Antonissen NJC, Wen Y, Armstrong SA
The dysregulation of developmental and stem cell associated genes is a common phenomenon during cancer development. Around half of acute myeloid leukemia (AML) patients express high levels of HOXA cluster genes and MEIS1. Most of these AML cases harbor an NPM1 mutation (NPM1c), which encodes for an oncogene mislocalized from the nucleolus to the cytoplasm. How NPM1c expression in hematopoietic cells leads to its characteristic gene expression pattern remains unclear. Here, we show that NPM1c directly binds to specific chromatin targets, which are co-occupied by the histone methyltransferase KMT2A (MLL1). Targeted degradation of NPM1c leads to a rapid decrease in gene expression and loss of RNA Polymerase II, as well as activating histone modifications at its targets. We demonstrate that NPM1c directly regulates oncogenic gene expression in collaboration with the MLL1 complex and define the mechanism by which MLL1-Menin small molecule inhibitors produce clinical responses in patients with NPM1-mutated AML.
Elife
Examining the Cooperation Between Extrachromosomal DNA Circles
Zhang J, Zhang CZ
In a departure from previous findings, new results suggest that free-floating pieces of DNA which carry additional copies of cancer-driving genes do not tend to cluster or have increased transcription.
JAMA Oncology
Ricciuti B, Awad MM
Expression of programmed cell death 1 (PD-1) ligand 1 (PD-L1) on tumor cells represents the most widely used clinical biomarker for predicting response to immune checkpoint inhibition in non?small cell lung cancer (NSCLC). However, even among advanced NSCLCs with high PD-L1 expression on 50% or more of tumor cells, only a minority of patients will respond to treatment with first-line PD-L1 inhibitors, such as pembrolizumab, atezolizumab, and cemiplimab, highlighting the pressing need to identify more effective therapeutic strategies as well as more precise biomarkers of immunotherapy activity in lung cancer.
JAMA Oncology
Lin NU, Krop I, Winer E
IMPORTANCE: It is estimated that up to 50% of patients with ERBB2 (HER2)-positive metastatic breast cancer (MBC) will develop brain metastases (BMs), which is associated with poor prognosis. Previous reports of the HER2CLIMB trial have demonstrated that tucatinib in combination with trastuzumab and capecitabine provides survival and intracranial benefits for patients with ERBB2-positive MBC and BMs.
OBJECTIVE: To describe overall survival (OS) and intracranial outcomes from tucatinib in combination with trastuzumab and capecitabine in patients with ERBB2-positive MBC and BMs with an additional 15.6 months of follow-up.
DESIGN, SETTING, AND PARTICIPANTS: HER2CLIMB is an international, multicenter, randomized, double-blind, placebo-controlled clinical trial evaluating tucatinib in combination with trastuzumab and capecitabine. The 612 patients, including those with active or stable BMs, had ERBB2-positive MBC previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine. The study was conducted from February 23, 2016, to May 3, 2019. Data from February 23, 2016, to February 8, 2021, were analyzed.
INTERVENTIONS: Patients were randomized 2:1 to receive tucatinib (300 mg orally twice daily) or placebo (orally twice daily), both in combination with trastuzumab (6 mg/kg intravenously or subcutaneously every 3 weeks with an initial loading dose of 8 mg/kg) and capecitabine (1000 mg/m2 orally twice daily on days 1-14 of each 3-week cycle).
MAIN OUTCOMES AND MEASURES: Evaluations in this exploratory subgroup analysis included OS and intracranial progression-free survival (CNS-PFS) in patients with BMs, confirmed intracranial objective response rate (ORR-IC) and duration of intracranial response (DOR-IC) in patients with measurable intracranial disease at baseline, and new brain lesion-free survival in all patients. Only OS was prespecified before the primary database lock.
RESULTS: At baseline, 291 of 612 patients (47.5%) had BMs. Median age was 52 years (range, 22-75 years), and 289 (99.3%) were women. At median follow-up of 29.6 months (range, 0.1-52.9 months), median OS was 9.1 months longer in the tucatinib-combination group (21.6 months; 95% CI, 18.1-28.5) vs the placebo-combination group (12.5 months; 95% CI, 11.2-16.9). The tucatinib-combination group showed greater clinical benefit in CNS-PFS and ORR-IC compared with the placebo-combination group. The DOR-IC was 8.6 months (95% CI, 5.5-10.3 months) in the tucatinib-combination group and 3.0 months (95% CI, 3.0-10.3 months) in the placebo-combination group. Risk of developing new brain lesions as the site of first progression or death was reduced by 45.1% in the tucatinib-combination group vs the placebo-combination group (hazard ratio, 0.55 [95% CI, 0.36-0.85]).
CONCLUSIONS AND RELEVANCE: This subgroup analysis found that tucatinib in combination with trastuzumab and capecitabine improved OS while reducing the risk of developing new brain lesions, further supporting the importance of this treatment option for patients with ERBB2-positive MBC, including those with BMs.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02614794.
Journal of Clinical Oncology
Adjuvant Endocrine Therapy in Premenopausal Breast Cancer: 12-Year Results from SOFT
Burstein HJ, Gelber RD, Regan MM
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The Suppression of Ovarian Function Trial (SOFT; ClinicalTrials.gov identifier: NCT00066690) randomly assigned premenopausal women with hormone receptor-positive breast cancer to 5 years of adjuvant tamoxifen, tamoxifen plus ovarian function suppression (OFS), or exemestane plus OFS. The primary analysis compared disease-free survival (DFS) between tamoxifen plus OFS versus tamoxifen alone; exemestane plus OFS versus tamoxifen was a secondary objective. After 8 years, SOFT reported a significant reduction in recurrence and improved overall survival (OS) with adjuvant tamoxifen plus OFS versus tamoxifen alone. Here, we report outcomes after median follow-up of 12 years. DFS remained significantly improved with tamoxifen plus OFS versus tamoxifen (hazard ratio, 0.82; 95% CI, 0.69 to 0.98) with a 12-year DFS of 71.9% with tamoxifen, 76.1% with tamoxifen plus OFS, and 79.0% with exemestane plus OFS. OS was improved with tamoxifen plus OFS versus tamoxifen (hazard ratio, 0.78; 95% CI, 0.60 to 1.01) and was 86.8% with tamoxifen, 89.0% with tamoxifen plus OFS, and 89.4% with exemestane plus OFS at 12 years. Among those who received prior chemotherapy for human epidermal growth factor receptor-2-negative tumors, OS was 78.8% with tamoxifen, 81.1% with tamoxifen plus OFS, and 84.4% with exemestane plus OFS. In conclusion, after 12 years, there remains a benefit from including OFS in adjuvant endocrine therapy, with an absolute improvement in OS more apparent with higher baseline risk of recurrence.
Journal of Clinical Oncology
A Process Framework for Ethically Deploying Artificial Intelligence in Oncology
Hantel A, Clancy DD, Kehl KL, Marron JM, Van Allen EM, Abel GA
Artificial Intelligence (AI) is an emerging technology that uses complex algorithms to arrive at an outcome over a range of circumstances, leveraging the ability of computer systems to perform tasks that would usually require human levels of intelligence. The use of AI in cancer care is rapidly expanding: a May 2022 PubMed search of the term cross-referenced with cancer revealed approximately 26,000 citations, with more than 60% published in the past five years. Ethical considerations for AI in oncology include patient equity, privacy, and autonomy; the roles of human- and machine-based judgment; and the patient-oncologist relationship. Relative to other parts of medicine, the implications of oncology AI are outsized, and some are idiosyncratic. Oncology AI tools apply to not one but two genomes (germline and somatic); can greatly complicate the existing weight of bias, discrimination, and structural racism in cancer care; and can subtly undermine patient and physician autonomy, leading to cancer care that is algorithmic rather than patient-centered. These diverse concerns, in the context of unreserved enthusiasm for AI, challenge a future where oncology AI is both widely implemented and ethically acceptable. We propose that adapting a process-focused approach for deploying AI in cancer care, such as the accountability for reasonableness framework (A4R), can address these concerns and realize a future where oncology AI is ethically deployed
Journal of Clinical Oncology
Development and Validation of the PREMMplus Model for Multigene Hereditary Cancer Risk Assessment
Yurgelun MB, Uno H, Furniss CS, Ukaegbu C, Horiguchi M, Chittenden A, Garber JE, Syngal S
PURPOSE: With the availability of multigene panel testing (MGPT) for hereditary cancer risk assessment, clinicians need to assess the likelihood of pathogenic germline variants (PGVs) across numerous genes in parallel. This study's aim was to develop and validate a clinical prediction model (PREMMplus) for MGPT risk assessment.
MATERIALS AND METHODS: PREMMplus was developed in a single-institution cohort of 7,280 individuals who had undergone MGPT. Logistic regression models with Least Absolute Shrinkage and Selection Operator regularization were used to examine candidate predictors (age, sex, ethnicity, and personal/family history of 18 cancers/neoplasms) to estimate one's likelihood of carrying PGVs in 19 genes (broadly categorized by phenotypic overlap and/or relative penetrance: 11 category A [APC, BRCA1/2, CDH1, EPCAM, MLH1, MSH2, MSH6, biallelic MUTYH, PMS2, and TP53] and eight category B genes [ATM, BRIP1, CDKN2A, CHEK2, PALB2, PTEN, RAD51C, and RAD51D]). Model performance was validated in nonoverlapping data sets of 8,691 and 14,849 individuals with prior MGPT ascertained from clinic- and laboratory-based settings, respectively.
RESULTS: PREMMplus (score 2.5%) had 93.9%, 91.7%, and 89.3% sensitivity and 98.3%, 97.5%, and 97.8% negative-predictive value (NPV) for identifying category A gene PGV carriers in the development and validation cohorts, respectively. PREMMplus assessment (score 2.5%) had 89.9%, 85.6%, and 84.2% sensitivity and 95.0%, 93.5%, and 93.5% NPV, respectively, for identifying category A/B gene PGV carriers. Decision curve analyses support MGPT for individuals predicted to have 2.5% probability of a PGV.
CONCLUSION: PREMMplus accurately identifies individuals with PGVs in a diverse spectrum of cancer susceptibility genes with high sensitivity/NPV. Individuals with PREMMplus scores 2.5% should be considered for MGPT.
Journal of Clinical Oncology
Haddad RI
PURPOSE: CheckMate 651 (ClinicalTrials.gov identifier: NCT02741570) evaluated first-line nivolumab plus ipilimumab versus EXTREME (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ six cycles, then cetuximab maintenance) in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
METHODS: Patients without prior systemic therapy for R/M SCCHN were randomly assigned 1:1 to nivolumab plus ipilimumab or EXTREME. Primary end points were overall survival (OS) in the all randomly assigned and programmed death-ligand 1 combined positive score (CPS) 20 populations. Secondary end points included OS in the programmed death-ligand 1 CPS 1 population, and progression-free survival, objective response rate, and duration of response in the all randomly assigned and CPS 20 populations.
RESULTS: Among 947 patients randomly assigned, 38.3% had CPS 20. There were no statistically significant differences in OS with nivolumab plus ipilimumab versus EXTREME in the all randomly assigned (median: 13.9 v 13.5 months; hazard ratio [HR], 0.95; 97.9% CI, 0.80 to 1.13; P = .4951) and CPS 20 (median: 17.6 v 14.6 months; HR, 0.78; 97.51% CI, 0.59 to 1.03; P = .0469) populations. In patients with CPS 1, the median OS was 15.7 versus 13.2 months (HR, 0.82; 95% CI, 0.69 to 0.97). Among patients with CPS 20, the median progression-free survival was 5.4 months (nivolumab plus ipilimumab) versus 7.0 months (EXTREME), objective response rate was 34.1% versus 36.0%, and median duration of response was 32.6 versus 7.0 months. Grade 3/4 treatment-related adverse events occurred in 28.2% of patients treated with nivolumab plus ipilimumab versus 70.7% treated with EXTREME.
CONCLUSION: CheckMate 651 did not meet its primary end points of OS in the all randomly assigned or CPS 20 populations. Nivolumab plus ipilimumab showed a favorable safety profile compared with EXTREME. There continues to be a need for new therapies in patients with R/M SCCHN.
Journal of the National Cancer Institute
Variation in Cardiac Dose Explains a "Fraction" of the Disparities Among Breast Cancer Patients
Punglia RS, Hassett MJ
Most studies on disparities in cancer have focused on differences in stage of diagnosis and access to treatment. Breast cancer death rates are highest among vulnerable populations, including Black women, the disadvantaged, older persons, and those living in rural settings. Few prior studies have investigated differences in the characteristics of administered treatments as a potential explanation for observed disparities in outcomes. In medical oncology, an analysis of chemotherapy administered to breast cancer patients found Black women received 10% lower relative dose intensity compared with White women. In this issue of the Journal, Dr Chapman and colleagues present a novel and intricate analysis of the mediators of racial disparities among women receiving whole breast radiation therapy, using mean heart dose as the vehicle for their examination.
Lancet Oncology
Morganti S, Tolaney SM
In 1976, approximately 50 years ago, the first randomised study leading to approval of adjuvant chemotherapy for breast cancer was reported. Chemotherapy remains a pillar of breast cancer treatment; however, in the past 50 years, we have learned that breast cancer is a heterogeneous disease and treatment should be tailored accordingly. We moved from a one-size-fits-all approach to a more personalised one, in which treatment decisions hinge upon the estimated risk of recurrence based not just on clinicopathological risk, but sometimes also on genomic information.
Nature Cancer
Bicarbonate Transport as a Vulnerability in Pancreatic Cancer
Qiang L, Dougan SK
Pancreatic ductal cells transport bicarbonate from blood to pancreatic juice. A study shows that pancreatic cancer retains SLC4A4-mediated bicarbonate import to fuel cancer growth via enhanced glycolysis and establish a pro-tumorigenic immune microenvironment. Targeting SLC4A4 mitigates acidosis and can be combined with checkpoint blockade.
Nature Communications
Breast Cancer Prevention by Short-Term Inhibition of TGFb Signaling
Aleckovic M, Cristea S, Gil Del Alcazar CR, Yan P, Ding L, Krop ED, Harper NW, Rojas Jimenez E,
Lu D, Gulvady AC, Foidart P, Seehawer M, Diciaccio B, Murphy KC, Pyrdol J, Anand J, Garza K, Wucherpfennig KW, Tamimi RM, Michor F, Polyak K
Cancer prevention has a profound impact on cancer-associated mortality and morbidity. We previously identified TGFb signaling as a candidate regulator of mammary epithelial cells associated with breast cancer risk. Here, we show that short-term TGFBR inhibitor (TGFBRi) treatment of peripubertal ACI inbred and Sprague Dawley outbred rats induces lasting changes and prevents estrogen- and carcinogen-induced mammary tumors, respectively. We identify TGFBRi-responsive cell populations by single cell RNA-sequencing, including a unique epithelial subpopulation designated secretory basal cells (SBCs) with progenitor features. We detect SBCs in normal human breast tissues and find them to be associated with breast cancer risk. Interactome analysis identifies SBCs as the most interactive cell population and the main source of insulin-IGF signaling. Accordingly, inhibition of TGFBR and IGF1R decrease proliferation of organoid cultures. Our results reveal a critical role for TGFŒ? in regulating mammary epithelial cells relevant to breast cancer and serve as a proof-of-principle cancer prevention strategy.
Nature Genetics
Liu I, Jiang L, Hack OA, Jeong D, Shaw ML, Englinger B, LaBelle J, Mire HM, Trissal M,
Panditharatna E, Vogelzang J, Suva ML, Ligon KL, Alexandrescu S, Arrillaga-Romany I, Gojo J,
Filbin MG
Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in diffuse midline gliomas (DMGs) of the childhood pons but are also increasingly recognized in adults. Their potential heterogeneity at different ages and midline locations is vastly understudied. Here, through dissecting the single-cell transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We show that stem-like oligodendroglial precursor-like cells, present across all clinico-anatomical groups, display varying levels of maturation dependent on location. We reveal a previously underappreciated relationship between mesenchymal cancer cell states and age, linked to age-dependent differences in the immune microenvironment. Further, we resolve the spatial organization of H3-K27M DMG cell populations and identify a mitotic oligodendroglial-lineage niche. Collectively, our study provides a powerful framework for rational modeling and therapeutic interventions.
New England Journal of Medicine
Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia
Brown JR
BACKGROUND: In a multinational, phase 3, head-to-head trial, ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, was compared with zanubrutinib, a BTK inhibitor with greater specificity, as treatment for relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). In prespecified interim analyses, zanubrutinib was superior to ibrutinib with respect to overall response (the primary end point). Data from the final analysis of progression-free survival are now available.
METHODS: We randomly assigned, in a 1:1 ratio, patients with relapsed or refractory CLL or SLL who had received at least one previous course of therapy to receive zanubrutinib or ibrutinib until the occurrence of disease progression or unacceptable toxic effects. In this final analysis, progression-free survival (a key secondary end point) was assessed with the use of a hierarchical testing strategy to determine whether zanubrutinib was noninferior to ibrutinib. If noninferiority was established, the superiority of zanubrutinib was assessed and claimed if the two-sided P value was less than 0.05.
RESULTS: At a median follow-up of 29.6 months, zanubrutinib was found to be superior to ibrutinib with respect to progression-free survival among 652 patients (hazard ratio for disease progression or death, 0.65; 95% confidence interval, [CI], 0.49 to 0.86; P‚Äâ=‚Äâ0.002), as assessed by the investigators; the results were similar to those as assessed by an independent-review committee. At 24 months, the investigator-assessed rates of progression-free survival were 78.4% in the zanubrutinib group and 65.9% in the ibrutinib group. Among patients with a 17p deletion, a TP53 mutation, or both, those who received zanubrutinib had longer progression-free survival than those who received ibrutinib (hazard ratio for disease progression or death, 0.53; 95% CI, 0.31 to 0.88); progression-free survival across other major subgroups consistently favored zanubrutinib. The percentage of patients with an overall response was higher in the zanubrutinib group than in the ibrutinib group. The safety profile of zanubrutinib was better than that of ibrutinib, with fewer adverse events leading to treatment discontinuation and fewer cardiac events, including fewer cardiac events leading to treatment discontinuation or death.
CONCLUSIONS: In patients with relapsed or refractory CLL or SLL, progression-free survival was significantly longer among patients who received zanubrutinib than among those who received ibrutinib, and zanubrutinib was associated with fewer cardiac adverse events. (Funded by BeiGene; ALPINE ClinicalTrials.gov number, NCT03734016.).
Proceedings of the National Academy of Sciences of the U.S.A.
CCAR2 Functions Downstream of the Shieldin Complex to Promote Double-Strand Break End-Joining
Iyer DR, Harada N, Clairmont C, Jiang L, Martignetti D, Nguyen H, He YJ, Chowdhury D, D'Andrea AD
The 53BP1-RIF1 pathway restricts the resection of DNA double-strand breaks (DSBs) and promotes blunt end-ligation by non-homologous end joining (NHEJ) repair. The Shieldin complex is a downstream effector of the 53BP1-RIF1 pathway. Here, we identify a component of this pathway, CCAR2/DBC1, which is also required for restriction of DNA end-resection. CCAR2 co-immunoprecipitates with the Shieldin complex, and knockout of CCAR2 in a BRCA1-deficient cell line results in elevated DSB end-resection, RAD51 loading, and PARP inhibitor (PARPi) resistance. Knockout of CCAR2 is epistatic with knockout of other Shieldin proteins. The S1-like RNA-binding domain of CCAR2 is required for its interaction with the Shieldin complex and for suppression of DSB end-resection. CCAR2 functions downstream of the Shieldin complex, and CCAR2 knockout cells have delayed resolution of Shieldin complex foci. Forkhead-associated (FHA)-dependent targeting of CCAR2 to DSB sites re-sensitized BRCA1-/-SHLD2-/- cells to PARPi. Taken together, CCAR2 is a functional component of the 53BP1-RIF1 pathway, promotes the refill of resected DSBs, and suppresses homologous recombination.
American Journal of Dermatopathology
Larocca C, Shanmugam V, Zemmour D, Antin JH, Lane AA
American Journal of Hematology
Follicular Lymphoma: 2023 Update on Diagnosis and Management
Jacobsen E
Annals of Applied Statistics
Loewinger G, Parmigiani G
Annals of Surgical Oncology
Tesch ME, Collins LC, Wong JS, Dominici L, Come SE, Partridge AH
Annals of Surgical Oncology
Tesch ME, Collins LC, Wong JS, Dominici L, Come SE, Partridge AH
Annals of Surgical Oncology
Kantor O, Burstein HJ, King TA, Winer EP, Mittendorf EA
Best Practice and Research Clinical Haematology
Consolidation Chemotherapy in AML: Are We Playing with a Full Deck of Cards?
Stone RM
Blood Advances
Liu Y, Valtis YK, Paolino JD, Place AE, Brunner AM, Weeks LD, Silverman LB, Vrooman LM,
Neuberg D, Stone RM, DeAngelo DJ, Luskin MR
Blood Cancer Discovery
Ten Hacken E, Sewastianik T, Yin S, Brunsting Hoffmann G, Clement K, Penter L, Redd RA, Ruthen N, Fell G, Parry EM, Lucas F, Baranowski K, Southard J, Joyal H, Billington L, Regis FFD, Witten E, Uduman M, Knisbacher BA, Li S, Lyu H, Davids MS, Getz G, Livak KJ, Neuberg DS, Carrasco RD, Wu CJ
Breast Cancer Research and Treatment
Breast Cancer Knowledge and Understanding Treatment Rationales Among Diverse Breast Cancer Survivors
Freedman RA, Lederman RI, Gagnon H, Gundersen DA, Revette AC, Odai-Afotey A, Kantor O, Keating NL
British Journal of Cancer
Shulman DS, Nag A, Thorner AR, Lessnick SL, Stegmaier K, Janeway KA, DuBois SG, Church AJ, Crompton BD
Cancer
Warren LEG, Niman SM, Remolano MC, Landry JM, Nakhlis F, Bellon JR, Aizer AA, Lin NU, Tolaney SM, Regan MM, Overmoyer BA, Lynce F
Cancer Immunology Research
Hippo Signaling Pathway Regulates Cancer Cell-Intrinsic MHC-II Expression
Zeng Z, Gu SS, Ouardaoui N, Tymm C, Yang L, Wong CJ, Li D, Zhang W, Wang X, Weirather JL,
Rodig SJ, Hodi FS, Brown M, Liu XS
Cancer Nursing
Translation of Evidence-Based Interventions Into Oncology Care Settings: An Integrative Review
Cooley ME, Hammer MJ
Cancer Research
Mitochondrial DNA Mutations as Natural Barcodes for Lineage Tracing of Murine Tumor Models
Penter L, Ten Hacken E, Southard J, Li S, Neuberg DS, Livak KJ, Wu CJ
Cancer Research
Williams HL, Dias Costa A, Zhang J, Raghavan S, Kapner KS, Ginebaugh SP, Väyrynen SA, Yuan C, Wang J, Yang A, Bosse TL, Kalekar RL, Lowder KE, Lau MC, Elganainy D, Morales-Oyarvide V, Rubinson DA, Singh H, Perez K, Cleary JM, Clancy TE, Wang J, Mancias JD, Brais LK, Hill ER,
Hahn WC, Aguirre AJ, Nowak JA, Wolpin BM
Clinical Advances in Hematology and Oncology
Energy Balance in Advanced Breast Cancer: Extending Beyond the Curative Setting
Ligibel JA
Clinical Cancer Research
Tsuji J, Li T, Grinshpun A, Coorens T, Russo D, Anderson L, Rees R, Nardone A, Patterson C,
Lennon NJ, Cibulskis C, Leshchiner I, Tayob N, Tolaney SM, Tung N, Krop IE, Winer EP, Stewart C, Getz G, Jeselsohn R
Clinical Cancer Research
Dias Costa A, Väyrynen SA, Zhang J, Väyrynen JP, Lau MC, Williams HL, Yuan C,
Morales-Oyarvide V, Elganainy D, Singh H, Cleary JM, Perez K, Ng K, Freed-Pastor W, Mancias JD, Dougan SK, Wang J, Rubinson DA, Brais L, Reilly E, Clancy T, Aguirre AJ, Wolpin BM, Nowak JA
Clinical Genitourinary Cancer
Mossanen M, Nassar AH, Stokes SM, Martinez-Chanza N, Kumar V, Nuzzo PV, Kwiatkowski DJ, Garber JE, Curran C, Freeman D, Preston M, Mouw KW, Kibel A, Choueiri TK, Sonpavde G, Rana HQ
Current Hematologic Malignancy Reports
Molecular Pathogenesis of Myeloproliferative Neoplasms
Rolles B, Mullally A
Current Opinion in Neurology
Immunotherapy Approaches for Adult Glioma: Knowledge Gained from Recent Clinical Trials
Andersen BM, Reardon DA
European Journal of Cancer
Choueiri TK
European Urology Oncology
Towards a Better Understanding of Antibody-Drug Conjugates in Urothelial Carcinoma
Labaki C, Bakouny Z, Sonpavde G, Choueiri TK, Van Allen EM
Genomics, Proteomics, and Bioinformatics
Zhang W, Roy Burman SS, Chen J, Donovan KA, Shu C, Zhang B, Zeng Z, Gu S, Zhang Y, Li D, Fischer ES, Tokheim C, Shirley Liu X
Gynecologic Oncology
Matulonis UA
Haematologica
Shimony S, Stone RM, DeAngelo DJ, Stahl M
Hematology, ASH Education Program
Selecting Initial Therapy in CLL
Ahn IE, Brown JR
Hematology, ASH Education Program
Sequencing Therapy in Relapsed DLBCL
Odejide OO
Hematology, ASH Education Program
Transplant for TP53-Mutated MDS and AML: Because We Can or Because We Should?
Lindsley RC
International Journal of Cancer
An International Report on Bacterial Communities in Esophageal Squamous Cell Carcinoma
Nomburg J, DeCaprio JA, Meyerson M
International Journal of Radiation Oncology, Biology, Physics
Yang DD, Huynh E, Williams CL, Han Z, Ampofo N, Vastola ME, Sangal P, Mak RH, Leeman JE,
Huynh MA
JAMA Otolaryngology – Head and Neck Surgery
Rettig EM, Wang AA, Tran NA, Carey E, Dey T, Schoenfeld JD, Sehgal K, Guenette JP, Margalit DN, Sethi R, Uppaluri R, Tishler RB, Annino DJ, Goguen LA, Jo VY, Haddad RI, Hanna GJ
JCO Oncology Practice
Roberts TJ, Sellars MC, Sands JM, Jacobson JO
JCO Oncology Practice
Jacobson JO, Peppercorn J
Journal of Cancer Education
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