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Dana-Farber Research Publication 7.1.2022

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July 1, 2022

This twice-monthly newsletter highlights the research endeavors at Dana-Farber Cancer Institute, noting recently published papers available from PubMed where Dana-Farber faculty are listed as first or senior authors. If you are a Dana-Farber faculty member and you think your paper is missing from Research News, please let us know at:

Cancer Cell

Bacterial Darth Vader: May the Force be with You

Polyak K

The microbiome has a major impact on tumor progression, yet the mechanisms are poorly defined. Fu et al. report in Cell that intracellular bacteria in a breast cancer model promote metastasis via reorganizing the cytoskeleton to enhance resistance to mechanical stress, thereby facilitating survival in the circulation during dissemination.

Journal of Clinical Oncology

Circulating Tumor DNA and Late Recurrence in High-Risk Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer

Lipsyc-Sharf M, Santos K, Patel A, Kirkner GJ, Hughes ME, Tolaney SM, Partridge AH, Krop IE, Winer EP, Lin NU, Parsons HA

PURPOSE: To examine the prevalence and dynamics of circulating tumor DNA (ctDNA) and its association with metastatic recurrence in patients with high-risk early-stage hormone receptor-positive breast cancer (HR+ BC) more than 5 years from diagnosis.
METHODS: We enrolled 103 patients with high-risk stage II-III HR+ BC diagnosed more than 5 years prior without clinical evidence of recurrence. We performed whole-exome sequencing (WES) on primary tumor tissue to identify somatic mutations tracked via a personalized, tumor-informed ctDNA test to detect minimal residual disease (MRD). We collected plasma at the time of consent and at routine visits every 6-12 months. Patients were followed for clinical recurrence.
RESULTS: In total, 85 of 103 patients had sufficient tumor tissue; of them, 83 of 85 (97.6%) patients had successful whole-exome sequencing. Personalized ctDNA assays were designed targeting a median of 36 variants to test 219 plasma samples. The median time from diagnosis to first sample was 8.4 years. The median follow-up was 10.4 years from diagnosis and 2.0 years from first sample. The median number of plasma samples per patient was two. Eight patients (10%) had positive MRD testing at any time point. Six patients (7.2%) developed distant metastatic recurrence, all of whom were MRD-positive before overt clinical recurrence, with median ctDNA lead time of 12.4 months. MRD was not identified in one patient (1.2%) with local recurrence. Two of eight MRD-positive patients had not had clinical recurrence at last follow-up.
CONCLUSION: In this prospective study, in patients with high-risk HR+ BC in the late adjuvant setting, ctDNA was identified a median of 1 year before all cases of distant metastasis. Future studies will determine if ctDNA-guided intervention in patients with HR+ BC can alter clinical outcomes.

Journal of Clinical Oncology

Impact of RxPONDER and monarchE on the Surgical Management of the Axilla in Patients with Breast Cancer

Mittendorf EA, King TA, Tolaney SM

Results of the RxPONDER and monarchE trials have informed systemic therapy recommendations for hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)–negative breast cancer. RxPONDER looked at the utility of the Oncotype DX Recurrence Score (RS) in determining chemotherapy benefit for patients with HR+ breast cancer and 1-3 positive nodes.1 The monarchE trial evaluated the cyclin-dependent kinase 4/6 inhibitor abemaciclib in the adjuvant setting for patients with high-risk early-stage HR+ disease.2 High-risk was defined as ≥ 4 pathologically positive axillary nodes or 1-3 positive nodes and at least one of the following: tumor size ≥ 5 cm, histologic grade 3 disease, or Ki‐67 ≥ 20%. Given the importance of the extent of nodal disease in these studies, surgical management of the axilla has resurfaced as a question asked at multidisciplinary tumor boards. Specifically, do these patients require axillary lymph node dissection (ALND) to determine total nodal burden to inform systemic therapy recommendations?

Journal of Clinical Oncology

Inequities in Alliance Acute Leukemia Clinical Trial and Biobank Participation: Defining Targets for Intervention

Hantel A, Stone RM, Lathan CS, DeAngelo DJ, Abel GA

PURPOSE: Representativeness in acute leukemia clinical research is essential for achieving health equity. The National Cancer Institute's mandate for Comprehensive Cancer Centers (CCCs) to define and assume responsibility for cancer control and treatment across a geographic catchment area provides an enforceable mechanism to target and potentially remediate participatory inequities.
METHODS: We examined enrollee characteristics across 15 Cancer and Leukemia Group B/Alliance cooperative group adult acute leukemia clinical trials (N = 3,734) from 1998 to 2013, including participation in optional companion biobanks. We determined enrollment odds by race-ethnicity for all participants adjusted for national incidence, and for those enrolled at CCCs adjusted for catchment area incidence. We modeled biobank participation by sociodemographics using logistic regression.
RESULTS: Non-Hispanic (NH)-White patients were more likely to be enrolled than NH-Black, NH-Asian, or Hispanic patients (odds ratio [OR] 0.75, 0.48, and 0.44, respectively; all P < .001), but less likely than NH-Native American patients (OR 1.91; P < .001), adjusted for national incidence. Enrollment odds were lower for NH-Black, NH-Asian, and Hispanic patients at CCCs adjusted for catchment area incidence (OR 0.57, 0.26, and 0.32, respectively; P < .001); differences were driven by overenrollment of NH-White patients from outside self-defined catchment areas (18.1% v 12.3%; χ2 P = .01) and by CCCs with less absolute enrollee diversity (rank sum P = .03). Among all enrollees, NH-White race-ethnicity and lower neighborhood deprivation correlated with biobank participation (OR 1.81 and 1.45, respectively; P = .01 and .03). For CCC enrollees, the correlation of race-ethnicity with biobank participation was attenuated by a measure accounting for their site's degree of enrollment disparity but not neighborhood deprivation.
CONCLUSION: Acute leukemia clinical research disparities are substantial and driven by structural trial enrollment barriers at CCCs. Real-time CCC access and enrollment monitoring is needed to better align research participation with local populations.

Journal of Clinical Oncology

Point/Counterpoint: Is It Time for Universal Germline Genetic Testing for all GI Cancers?

Yurgelun MB

Use of germline genetic testing among patients with cancer is increasing because of (1) the availability of multigene panel tests that include multiple cancer susceptibility genes in a single test, (2) decreased costs of these tests and improvements in insurance coverage, and (3) US Food and Drug Administration-approval of genotype-directed therapies such as poly(ADP-ribose) polymerase inhibitors for individuals with certain cancers and pathogenic germline variants in BRCA1 and BRCA2 (with possible benefits with other genes in the homologous repair deficiency pathway). In addition, National Comprehensive Cancer Network guidelines have already endorsed germline genetic testing for all patients with certain cancer types (epithelial ovarian cancer, exocrine pancreatic cancer, and high-grade/metastatic prostate cancer), regardless of age or personal/family history of cancer. Herein, we debate the pros and cons of offering germline multigene panel testing to all patients diagnosed with any GI cancer. The authors agree that it may just be a matter of time before germline multigene panel testing is offered to all patients with cancer; however, this article will highlight some of the benefits, risks, and limitations of this approach so that research can help fill some of the gaps to ensure that genetic medicine continues to be implemented in ways that improve real-world patient care and outcomes.

Journal of the National Cancer Institute

Overcoming Obstacles in Transitions of Cancer Survivor Care

Morgans AK, Partridge AH

The past several decades have witnessed a dramatic revolution in the approach to cancer survivorship care. In 2005, the Institute of Medicine’s (IOM’s) report From Cancer Patient to Cancer Survivor: Lost in Transition highlighted growing concerns that the unique needs of the cancer survivor population, at that time comprising more than 10 million individuals in the United States, were understudied by our research community and underrecognized by the care delivery system. Subsequently, there has been global recognition that the experience of having had cancer has become a chronic condition for many survivors who are living for years and sometimes decades with the combined consequences of the disease and its treatment. As therapeutic advances today continue to transform those afflicted with cancer into those living with cancer or a history of cancer, the population of cancer survivors continues to grow, with 26.1 million cancer survivors projected to be living in the United States alone in 2040. Attending to the medical demands of this burgeoning population requires addressing the clinical needs of people living after cancer diagnosis and treatment, adjusting care to meet evolving needs over time, and training a sufficiently sized and trained workforce to provide that care.

Lancet Oncology

Cancer in sub-Saharan Africa: A Lancet Oncology Commission

Ngwa W, Bih N, Rebbeck TR

In sub-Saharan Africa (SSA), urgent action is needed to curb a growing crisis in cancer incidence and mortality. Without rapid interventions, data estimates show a major increase in cancer mortality from 520‚Äâ348 in 2020 to about 1 million deaths per year by 2030. Here, we detail the state of cancer in SSA, recommend key actions on the basis of analysis, and highlight case studies and successful models that can be emulated, adapted, or improved across the region to reduce the growing cancer crises. Recommended actions begin with the need to develop or update national cancer control plans in each country. Plans must include childhood cancer plans, managing comorbidities such as HIV and malnutrition, a reliable and predictable supply of medication, and the provision of psychosocial, supportive, and palliative care. Plans should also engage traditional, complementary, and alternative medical practices employed by more than 80% of SSA populations and pathways to reduce missed diagnoses and late referrals. More substantial investment is needed in developing cancer registries and cancer diagnostics for core cancer tests. We show that investments in, and increased adoption of, some approaches used during the COVID-19 pandemic, such as hypofractionated radiotherapy and telehealth, can substantially increase access to cancer care in Africa, accelerate cancer prevention and control efforts, increase survival, and save billions of US dollars over the next decade. The involvement of African First Ladies in cancer prevention efforts represents one practical approach that should be amplified across SSA. Moreover, investments in workforce training are crucial to prevent millions of avoidable deaths by 2030. We present a framework that can be used to strategically plan cancer research enhancement in SSA, with investments in research that can produce a return on investment and help drive policy and effective collaborations. Expansion of universal health coverage to incorporate cancer into essential benefits packages is also vital. Implementation of the recommended actions in this Commission will be crucial for reducing the growing cancer crises in SSA and achieving political commitments to the UN Sustainable Development Goals to reduce premature mortality from non-communicable diseases by a third by 2030.

Lancet Oncology

Nivolumab Plus Cabozantinib Versus Sunitinib in First-Line Treatment for Advanced Renal Cell Carcinoma (CheckMate 9ER): Long-Term Follow-Up Results from an Open-Label, Randomised, Phase 3 Trial

Choueiri TK

BACKGROUND: In the primary analysis of CheckMate 9ER, nivolumab plus cabozantinib showed superior progression-free survival, overall survival, and objective response over sunitinib in patients with previously untreated advanced renal cell carcinoma (median follow-up of 18·1 months). Here, we report extended follow-up of overall survival and updated efficacy and safety.
METHODS: This open-label, randomised, phase 3 trial was done in 125 hospitals and cancer centres across 18 countries. We included patients aged 18 years or older with previously untreated advanced or metastatic clear-cell renal cell carcinoma, a Karnofsky performance status of 70% or higher, measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 assessed by the investigator, any International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk category, and available tumour tissue for PD-L1 testing. Patients were randomly assigned (1:1) to nivolumab (240 mg) intravenously every 2 weeks plus cabozantinib (40 mg) orally once daily or sunitinib (50 mg orally) once daily (4 weeks per 6-week cycle). Randomisation, stratified by IMDC risk status, tumour PD-L1 expression, and geographical region, was done by permuted block within each stratum using a block size of four, via an interactive response system. The primary endpoint was progression-free survival by blinded independent central review. Overall survival was a secondary endpoint (reported here as the preplanned final analysis according to the protocol). Efficacy was assessed in all randomly assigned patients; safety was assessed in all patients who received at least one dose of any study drug. This ongoing study, closed to recruitment, is registered with, NCT03141177.
FINDINGS: Between Sept 11, 2017, and May 14, 2019, 323 patients were randomly assigned to the nivolumab plus cabozantinib group and 328 to the sunitinib group. With an extended follow-up (data cutoff of June 24, 2021; median 32·9 months [IQR 30·4-35·9]), median overall survival was 37·7 months (95% CI 35·5-not estimable) in the nivolumab plus cabozantinib group and 34·3 months (29·0-not estimable) in the sunitinib group (hazard ratio [HR] 0·70 [95% CI 0·55-0·90], p=0·0043) and updated median progression-free survival was 16·6 months (12·8-19·8) versus 8·3 months (7·0-9·7; HR 0·56 [95% CI 0·46-0·68], p<0·0001). Grade 3-4 treatment-related adverse events occurred in 208 (65%) of 320 patients with nivolumab plus cabozantinib versus 172 (54%) of 320 with sunitinib. The most common grade 3-4 treatment-related adverse events were hypertension (40 [13%] of 320 patients in the nivolumab plus cabozantinib group vs 39 [12%] of 320 in the sunitinib group), palmar-plantar erythrodysaesthesia (25 [8%] vs 26 [8%]), and diarrhoea (22 [7%] vs 15 [5%]). Grade 3-4 treatment-related serious adverse events occurred in 70 (22%) of 320 patients in the nivolumab plus cabozantinib group and 31 (10%) of 320 in the cabozantinib group. One additional treatment-related death occurred with sunitinib (sudden death).
INTERPRETATION: With extended follow-up and preplanned final overall survival analysis per protocol, nivolumab plus cabozantinib demonstrated improved efficacy versus sunitinib, further supporting the combination in the first-line treatment of advanced renal cell carcinoma.
FUNDING: Bristol Myers Squibb and Ono Pharmaceutical.

Nature Communications

RNF43 G659fs is an Oncogenic Colorectal Cancer Mutation and Sensitizes Tumor Cells to PI3K/mTOR Inhibition

Fang L, Ford-Roshon D, Russo M, O'Brien C, Xiong X, Gurjao C, Grandclaudon M, Raghavan S, Corsello SM, Carr SA, Udeshi ND, Berstler J, Sicinska E, Ng K, Giannakis M

The RNF43_p.G659fs mutation occurs frequently in colorectal cancer, but its function remains poorly understood and there are no specific therapies directed against this alteration. In this study, we find that RNF43_p.G659fs promotes cell growth independent of Wnt signaling. We perform a drug repurposing library screen and discover that cells with RNF43_p.G659 mutations are selectively killed by inhibition of PI3K signaling. PI3K/mTOR inhibitors yield promising antitumor activity in RNF43659mut isogenic cell lines and xenograft models, as well as in patient-derived organoids harboring RNF43_p.G659fs mutations. We find that RNF43659mut binds p85 leading to increased PI3K signaling through p85 ubiquitination and degradation. Additionally, RNA-sequencing of RNF43659mut isogenic cells reveals decreased interferon response gene expression, that is reversed by PI3K/mTOR inhibition, suggesting that RNF43659mut may alter tumor immunity. Our findings suggest a therapeutic application for PI3K/mTOR inhibitors in treating RNF43_p.G659fs mutant cancers.

Nature Genetics

Allelic Imbalance of Chromatin Accessibility in Cancer Identifies Candidate Causal Risk Variants and Their Mechanisms

Grishin D, Gusev A

While many germline cancer risk variants have been identified through genome-wide association studies (GWAS), the mechanisms by which these variants operate remain largely unknown. Here we used 406 cancer ATAC-Seq samples across 23 cancer types to identify 7,262 germline allele-specific accessibility QTLs (as-aQTLs). Cancer as-aQTLs had stronger enrichment for cancer risk heritability (up to 145 fold) than any other functional annotation across seven cancer GWAS. Most cancer as-aQTLs directly altered transcription factor (TF) motifs and exhibited differential TF binding and gene expression in functional screens. To connect as-aQTLs to putative risk mechanisms, we introduced the regulome-wide associations study (RWAS). RWAS identified genetically associated accessible peaks at >70% of known breast and prostate loci and discovered new risk loci in all examined cancer types. Integrating as-aQTL discovery, motif analysis and RWAS identified candidate causal regulatory elements and their probable upstream regulators. Our work establishes cancer as-aQTLs and RWAS analysis as powerful tools to study the genetic architecture of cancer risk.

Nature Genetics

SMARCE1 Deficiency Generates a Targetable mSWI/SNF Dependency in Clear Cell Meningioma

St Pierre R, Collings CK, Samé Guerra DD, Widmer CJ, Bolonduro O, Mashtalir N, Sankar A, Liang Y, Bi WL, Ramesh V, Qi J, Meredith DM, Kadoch C

Mammalian SWI/SNF (mSWI/SNF) ATP-dependent chromatin remodeling complexes establish and maintain chromatin accessibility and gene expression, and are frequently perturbed in cancer. Clear cell meningioma (CCM), an aggressive tumor of the central nervous system, is uniformly driven by loss of SMARCE1, an integral subunit of the mSWI/SNF core. Here, we identify a structural role for SMARCE1 in selectively stabilizing the canonical BAF (cBAF) complex core-ATPase module interaction. In CCM, cBAF complexes fail to stabilize on chromatin, reducing enhancer accessibility, and residual core module components increase the formation of BRD9-containing non-canonical BAF (ncBAF) complexes. Combined attenuation of cBAF function and increased ncBAF complex activity generates the CCM-specific gene expression signature, which is distinct from that of NF2-mutated meningiomas. Importantly, SMARCE1-deficient cells exhibit heightened sensitivity to small-molecule inhibition of ncBAF complexes. These data inform the function of a previously elusive SWI/SNF subunit and suggest potential therapeutic approaches for intractable SMARCE1-deficient CCM tumors.

Nature Methods

Metagenome Assembly of High-Fidelity Long Reads with Hifiasm-Meta

Feng X, Cheng H, Li H

De novo assembly of metagenome samples is a common approach to the study of microbial communities. Current metagenome assemblers developed for short sequence reads or noisy long reads were not optimized for accurate long reads. We thus developed hifiasm-meta, a metagenome assembler that exploits the high accuracy of recent data. Evaluated on seven empirical datasets, hifiasm-meta reconstructed tens to hundreds of complete circular bacterial genomes per dataset, consistently outperforming other metagenome assemblers.

New England Journal of Medicine

Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRAS(G12C) Mutation

Jänne PA, Heist RS

BACKGROUND: Adagrasib, a KRASG12C inhibitor, irreversibly and selectively binds KRASG12C, locking it in its inactive state. Adagrasib showed clinical activity and had an acceptable adverse-event profile in the phase 1-1b part of the KRYSTAL-1 phase 1-2 study.
METHODS: In a registrational phase 2 cohort, we evaluated adagrasib (600 mg orally twice daily) in patients with KRASG12C -mutated non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy and anti-programmed death 1 or programmed death ligand 1 therapy. The primary end point was objective response assessed by blinded independent central review. Secondary end points included the duration of response, progression-free survival, overall survival, and safety.
RESULTS: As of October 15, 2021, a total of 116 patients with KRASG12C -mutated NSCLC had been treated (median follow-up, 12.9 months); 98.3% had previously received both chemotherapy and immunotherapy. Of 112 patients with measurable disease at baseline, 48 (42.9%) had a confirmed objective response. The median duration of response was 8.5 months (95% confidence interval [CI], 6.2 to 13.8), and the median progression-free survival was 6.5 months (95% CI, 4.7 to 8.4). As of January 15, 2022 (median follow-up, 15.6 months), the median overall survival was 12.6 months (95% CI, 9.2 to 19.2). Among 33 patients with previously treated, stable central nervous system metastases, the intracranial confirmed objective response rate was 33.3% (95% CI, 18.0 to 51.8). Treatment-related adverse events occurred in 97.4% of the patients - grade 1 or 2 in 52.6% and grade 3 or higher in 44.8% (including two grade 5 events) - and resulted in drug discontinuation in 6.9% of patients.
CONCLUSIONS: In patients with previously treated KRASG12C -mutated NSCLC, adagrasib showed clinical efficacy without new safety signals. (Funded by Mirati Therapeutics; number, NCT03785249.).

New England Journal of Medicine

Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma

Richardson PG, Jacobus SJ, Weller EA, Raje NS, Yee AJ, Fulciniti M, Hebert K, Samur MK, Masone K, Maglio ME, Zeytoonjian AA, Nadeem O, Schlossman RL, Laubach JP, Paba-Prada C, Ghobrial IM, Anderson KC, Munshi NC

BACKGROUND: In patients with newly diagnosed multiple myeloma, the effect of adding autologous stem-cell transplantation (ASCT) to triplet therapy (lenalidomide, bortezomib, and dexamethasone [RVD]), followed by lenalidomide maintenance therapy until disease progression, is unknown.
METHODS: In this phase 3 trial, adults (18 to 65 years of age) with symptomatic myeloma received one cycle of RVD. We randomly assigned these patients, in a 1:1 ratio, to receive two additional RVD cycles plus stem-cell mobilization, followed by either five additional RVD cycles (the RVD-alone group) or high-dose melphalan plus ASCT followed by two additional RVD cycles (the transplantation group). Both groups received lenalidomide until disease progression, unacceptable side effects, or both. The primary end point was progression-free survival.
RESULTS: Among 357 patients in the RVD-alone group and 365 in the transplantation group, at a median follow-up of 76.0 months, 328 events of disease progression or death occurred; the risk was 53% higher in the RVD-alone group than in the transplantation group (hazard ratio, 1.53; 95% confidence interval [CI], 1.23 to 1.91; P<0.001); median progression-free survival was 46.2 months and 67.5 months. The percentage of patients with a partial response or better was 95.0% in the RVD-alone group and 97.5% in the transplantation group (P = 0.55); 42.0% and 46.8%, respectively, had a complete response or better (P = 0.99). Treatment-related adverse events of grade 3 or higher occurred in 78.2% and 94.2%, respectively; 5-year survival was 79.2% and 80.7% (hazard ratio for death, 1.10; 95% CI, 0.73 to 1.65).
CONCLUSIONS: Among adults with multiple myeloma, RVD plus ASCT was associated with longer progression-free survival than RVD alone. No overall survival benefit was observed. (Funded by the National Heart, Lung, and Blood Institute and others; DETERMINATION number, NCT01208662.).

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

Memory-Like NK Cells Armed with a Neoepitope-specific CAR Exhibit Potent Activity Against NPM1 Mutated Acute Myeloid Leukemia

Dong H, Vergara J, Liang Y, Ali A, Tarannum M, Baginska J, Abdulhamid Y, Dinh K, Soiffer RJ, Ritz J, Glimcher LH, Romee R

Acute myeloid leukemia (AML) remains a therapeutic challenge, and a paucity of tumor-specific targets has significantly hampered the development of effective immune-based therapies. Recent paradigm-changing studies have shown that natural killer (NK) cells exhibit innate memory upon brief activation with IL-12 and IL-18, leading to cytokine-induced memory-like (CIML) NK cell differentiation. CIML NK cells have enhanced antitumor activity and have shown promising results in early phase clinical trials in patients with relapsed/refractory AML. Here, we show that arming CIML NK cells with a neoepitope-specific chimeric antigen receptor (CAR) significantly enhances their antitumor responses to nucleophosphmin-1 (NPM1)-mutated AML while avoiding off-target toxicity. CIML NK cells differentiated from peripheral blood NK cells were efficiently transduced to express a TCR-like CAR that specifically recognizes a neoepitope derived from the cytosolic oncogenic NPM1-mutated protein presented by HLA-A2. These CAR CIML NK cells displayed enhanced activity against NPM1-mutated AML cell lines and patient-derived leukemic blast cells. CAR CIML NK cells persisted in vivo and significantly improved AML outcomes in xenograft models. Single-cell RNA sequencing and mass cytometry analyses identified up-regulation of cell proliferation, protein folding, immune responses, and major metabolic pathways in CAR-transduced CIML NK cells, resulting in tumor-specific, CAR-dependent activation and function in response to AML target cells. Thus, efficient arming of CIML NK cells with an NPM1-mutation-specific TCR-like CAR substantially improves their innate antitumor responses against an otherwise intracellular mutant protein. These preclinical findings justify evaluating this approach in clinical trials in HLA-A2+ AML patients with NPM1c mutations.

American Journal of Clinical Nutrition

Sugar-Sweetened Beverage and Sugar Consumption and Colorectal Cancer Incidence and Mortality According to Anatomic Subsite

Yuan C, Joh HK, Wang QL, Zhang Y, Smith-Warner SA, Wang M, Song M, Zhang X, Zoltick ES, Hur J, Chan AT, Meyerhardt JA, Ogino S, Ng K, Giovannucci EL, Wu K

American Journal of Human Genetics

Germline Predisposition to Pediatric Ewing Sarcoma is Characterized by Inherited Pathogenic Variants in DNA Damage Repair Genes

Gillani R, Camp SY, Han S, Jones JK, Chu H, Gusev A, Kamihara J, Janeway KA, Crompton BD, AlDubayan SH, Van Allen EM

Annals of Surgical Oncology

How Often Does Retrieval of a Clipped Lymph Node Change Adjuvant Therapy Recommendations? A Prospective, Consecutive, Patient Cohort Study

Weiss A, King C, Grossmith S, Portnow L, Raza S, Nakhlis F, Dominici L, Barbie T, Minami C, Nimbkar S, Rhei E, Mittendorf EA, King TA

Blood Advances

A New Role for the SRC Family Kinase HCK as a Driver of SYK Activation in MYD88 Mutated Lymphomas

Munshi M, Liu X, Kofides A, Tsakmaklis N, Guerrera ML, Hunter ZR, Patterson CJ, Canning AG, Meid K, Gustine J, Branagan AR, Flynn CA, Sarosiek S, Castillo JJ, Wang J, Buhrlage SJ, Gray NS, Munshi NC, Anderson KC, Treon SP, Yang G

Breast Cancer Research and Treatment

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

Tolaney SM

Breast Cancer Research and Treatment

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

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

Breast Cancer Research and Treatment

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

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

Cancer Immunology Research

Activation of Tumor-Cell STING Primes NK-Cell Therapy

Knelson EH, Ivanova EV, Tarannum M, Campisi M, Lizotte PH, Booker MA, Ozgenc I, Noureddine M, Meisenheimer B, Chen M, Piel B, Spicer N, Obua B, Shannon E, Mahadevan NR, Schol PJ, Lee-Hassett AM, Zlota A, Vo HV, Ha M, Bertram AA, Han S, Thai TC, Gustafson CE, Haggerty TJ, Albertson TP, Hartley AV, Eser PO, Li ZH, Vivero M, De Rienzo A, Richards WG, Smith EL, Janne PA, Tolstorukov MY, Romee R, Paweletz CP, Bueno R, Barbie DA

Cancer Immunology Research

Insights into Immune Escape During Tumor Evolution and Response to Immunotherapy Using a Rat Model of Breast Cancer

Gil Del Alcazar CR, Trinh A, Alečković M, Rojas Jimenez E, Harper NW, Oliphant MUJ, Xie S, Krop ED, Lulseged B, Murphy KC, Keenan TE, Van Allen EM, Tolaney SM, Freeman GJ, Dillon DA, Muthuswamy SK, Polyak K

Cancer Medicine

Derivation and Validation of a Risk Classification Tree for Patients with Synovial Sarcoma

Neel DV, Collins NB, Hornick JL, Demetri GD, Shulman DS

Cancer Research

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

Zhang Z, Golomb L, Meyerson M

Clinical Cancer Research

A Phase I Study Investigating AZD8186, a Potent and Selective Inhibitor of PI3Kβ/δ, in Patients with Advanced Solid Tumors

Choudhury AD, Shapiro GI

Clinical Cancer Research

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

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

Clinical Cancer Research

Circulating Tumor DNA Is Associated with Response and Survival in Patients with Advanced Leiomyosarcoma

Madanat-Harjuoja LM, Klega K, Shulman DS, Thorner AR, Nag A, Tap WD, Diller L, George S, Crompton BD

Clinical Cancer Research

Facts and Hopes in the Relationship of EBV with Cancer Immunity and Immunotherapy

Zhang B

Clinical Cancer Research

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

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

Clinical Cancer Research

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

Sweeney CJ

Clinical Cancer Research

Preclinical Modeling of Leiomyosarcoma Identifies Susceptibility to Transcriptional CDK Inhibitors through Antagonism of E2F-Driven Oncogenic Gene Expression

Hemming ML, Bhola P, Loycano MA, Anderson JA, Taddei ML, Doyle LA, Lavrova E, Andersen JL, Klega KS, Benson MR, Crompton BD, Raut CP, George S, Letai A, Demetri GD, Sicinska E

Clinical Drug Investigation

Report of the First International Symposium on NUT Carcinoma

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

Clinical Cancer Research

Somatic and Germline Genomic Alterations in Very Young Women with Breast Cancer

Waks AG, Kim D, Jain E, Snow C, Kirkner GJ, Rosenberg SM, Oh C, Poorvu PD, Peppercorn J, Come SE, Brachtel EF, Collins LC, Partridge AH, Wagle N

Clinical Drug Investigation

Temporal Trends in Grade 3/4 Adverse Events and Associated Costs of Nivolumab Plus Cabozantinib Versus Sunitinib for Previously Untreated Advanced Renal Cell Carcinoma

Choueiri TK, McGregor B

Critical Reviews in Oncology Hematology

Exercise Oncology During and Beyond the COVID-19 Pandemic: Are Virtually Supervised Exercise Interventions a Sustainable Alternative?

Gonzalo-Encabo P, Wilson RL, Kang DW, Normann AJ, Dieli-Conwright CM

Current Opinion in Immunology

Editorial Overview: Vaccines: Reinvigorating Therapeutic Cancer Vaccines

Robles-Oteiza C, Wu CJ


Analysis of a SARS-CoV-2 Convalescent Cohort Identified a Common Strategy for Escape of Vaccine-Induced Anti-RBD Antibodies by Beta and Omicron Variants

Chang MR, Ke H, Coherd CD, Wang Y, Mashima K, Kastrunes GM, Marasco WA

EMBO Journal

Atossa: A Royal Link Between OXPHOS Metabolism and Macrophage Migration

Latorre-Muro P, Puigserver P

Future Oncology

A Phase II Clinical Trial of Neoadjuvant Sasanlimab and Stereotactic Body Radiation Therapy as an In Situ Vaccine for Cisplatin-Ineligible MIBC: the RAD VACCINE MIBC Trial

Sonpavde GP


Cardiovascular Adverse Events in Patients with Chronic Lymphocytic Leukemia Receiving Acalabrutinib Monotherapy: Pooled Analysis of 762 Patients

Brown JR

Head and Neck

Association Between Radiation Dose to Organs at Risk and Acute Patient Reported Outcome During Radiation Treatment for Head and Neck Cancers

Arbab M, Chen YH, Tishler RB, Gunasti L, Glass J, Fugazzotto JA, Killoran JH, Sethi R, Rettig E, Annino D, Goguen L, Uppaluri R, Hsu C, Burke E, Hanna GJ, Haddad RI, Margalit DN, Schoenfeld JD

Hematology/Oncology Clinics of North America

Colorectal Cancer: Advancing Science, Improving Access, and Refining Therapy

Schlechter BL, Ng K

Hematology/Oncology Clinics of North America

Impact of Diet and Exercise on Colorectal Cancer

Meyerhardt JA

Hematology/Oncology Clinics of North America

Management of Rectal Cancer

Schlechter BL


Multiple High-Grade and Rare Immune-Related Adverse Events in a Colon Cancer Patient with Genomic and Cytokine Profiling

Tyan K, Abu-Shawer O, Baginska J, Severgnini M, Manos M, Vaitkevicius H, Grover S, Hodi FS, Rahma OE

International Journal of Radiation Oncology, Biology, Physics

In Reply to Yilmaz et al

Bellon JR, Tolaney SM

Journal of Adolescent and Young Adult Oncology

The Effect of Pediatric Cancer on Identity in Young Adult Survivors: Results from Project REACH

Chevalier LL, Zwemer EK, Casey R, Recklitis CJ

Journal of the American Academy of Dermatology

Cutaneous Langerhans Cell Histiocytosis in Adults: A Retrospective Cohort Study of Adult Patients Presenting to a Single Academic Cancer Center Between 2003 and 2017

Bui AN, Larocca C, Giobbie-Hurder A, Jacobsen ED, LeBoeuf NR

Journal of the American Geriatrics Society

Geriatric Surgical Service Interventions in Older Emergency General Surgery Patients: Preliminary Results

Hu FY, O'Mara L, Tulebaev S, Orkaby AR, Cooper Z, Bernacki RE

Journal of Clinical Investigation

Expansion, Persistence, and Efficacy of Donor Memory-Like NK Cells Infused for Posttransplant Relapse

Shapiro RM, Birch GC, Vergara Cadavid J, Nikiforow S, Baginska J, Ali AK, Tarannum M, Sheffer M, Abdulhamid YZ, Rambaldi B, Arihara Y, Reynolds C, Halpern MS, Rodig SJ, Cullen N, Wolff JO,  Pfaff KL, Lane AA, Lindsley RC, Cutler CS, Antin JH, Ho VT, Koreth J, Gooptu M, Kim HT, Wu CJ, Soiffer RJ, Ritz J, Romee R

Journal of Medicinal Chemistry

The Dawn of Allosteric BCR-ABL1 Drugs: From a Phenotypic Screening Hit to an Approved Drug

Teng M, Luskin MR

Journal of Palliative Medicine

Cancer Patients' Experiences with and Perspectives on the Medicinal Cannabis "High"

Tung SC, Nayak MM, Chai PR, Tulsky J, Sannes TS, Yusufov M, Braun IM

Journal of Thoracic Oncology

Concurrent TP53 Mutations Facilitate Resistance Evolution in EGFR-Mutant Lung Adenocarcinoma

Chambers E, Nguyen T, Coolidge A, Lydon CA, Sholl L, Nishino M, Van Allen EM, Jänne PA

Journal of Thoracic Oncology

Reply to Kus and Aktas

Ricciuti B, Awad MM

JAMA Psychiatry

Effect of Culturally Tailored, Internet-Delivered Cognitive Behavioral Therapy for Insomnia in Black Women: A Randomized Clinical Trial

Zhou ES

JCO Oncology Practice

Breast Medical Oncologists' Perspectives of Telemedicine for Breast Cancer Care: A Survey Study

Stavrou E, Qiu J, Zafar A, Tramontano AC, Isakoff S, Winer E, Manz C

JMIR Medical Informatics

Associations Between Family Member Involvement and Outcomes of Patients Admitted to the Intensive Care Unit: Retrospective Cohort Study

Gray TF, Kwok A, Do KM, Zeng S, Moseley ET, Dbeis YM, Umeton R, Tulsky JA, El-Jawahri A, Lindvall 


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

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


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

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

Lung Cancer

Adjust, Don't Avoid: The Need for Risk-Based CT Screening in Nonsmoking Populations

Swami N, Chen TY, Duma N

Nature Reviews Cancer

Targeting CDK4 and CDK6 in Cancer

Bergholz JS, Zhao JJ


Liquid Biopsy in Gliomas: A RANO Review and Proposals for Clinical Applications

Warren KE, Wen PY

Nucleic Acids Research

The Metaphorical Swiss Army Knife: The Multitude and Diverse Roles of HEAT Domains in Eukaryotic Translation Initiation

Friedrich D, Arthanari H


Addiction of Merkel Cell Carcinoma to MUC1-C Identifies a Potential New Target for Treatment

Morimoto Y, Fushimi A, Yamashita N, Hagiwara M, Bhattacharya A, Cheng J, Frost TC, Ahmad R, Daimon T, Hata T, Takahashi H, Yamamoto M, Suzuki Y, DeCaprio JA, Kufe D

Pediatric Blood and Cancer

End-of-Life Care Quality for Children with Cancer Who Receive Palliative Care

Wolfe J

Pediatric Transplantation

Comparison of Toxicity Following Single Versus Tandem Autologous Transplant Regimens for Pediatric Medulloblastoma

Ma C, Al-Sayegh H, Shyr D, Lehmann LE, Chi SN


The Art of Saying Nothing

Mack JW


Radiomics-Based Cluster Groups to Predict Clinical-Pathologic and Genomic Characteristics of Stage I Lung Adenocarcinoma

Nishino M

Science Immunology

Selfish Antibodies Target Auto-Antigens in Cancer

Reyna ÁG, Griffin GK

Small Methods

A Robust Method for Perfusable Microvascular Network Formation In Vitro

Wan Z, Shelton SE, Lorch JH, Barbie DA

Statistics in Medicine

A Multivariate Parametric Empirical Bayes Screening Approach for Early Detection of Hepatocellular Carcinoma Using Multiple Longitudinal Biomarkers

Tayob N

World Neurosurgery

Incidence and Predictors of Neurologic Death in Patients with Brain Metastases

Lamba N, Catalano PJ, Cagney DN, Wen PY, Aizer AA