1,582 results match your criteria: "Dana-Farber Cancer Institute and Harvard Medical School[Affiliation]"

Article Synopsis
  • Bruton tyrosine kinase inhibitors (BTKi) have significantly improved treatment for B-cell malignancies, but many patients stop using them due to side effects, with cardiac issues being the most common reason for discontinuation.* -
  • The BRUIN study tested pirtobrutinib, a new non-covalent BTKi, on 127 patients who were intolerant to previous BTKi treatments, finding that many experienced fewer or no cardiac issues while showing a high overall response rate.* -
  • Results indicated pirtobrutinib had a median time on treatment of 15.3 months, with notable side effects like fatigue and neutropenia; overall, it proved to be a safe and effective alternative for
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The Epigenetic Hallmarks of Cancer.

Cancer Discov

October 2024

Department of Epigenetics, Van Andel Institute, Grand Rapids, Michigan.

Article Synopsis
  • Cancer is a complex disease influenced by various molecular and cellular processes, now including "nonmutational epigenetic reprogramming" as a new hallmark.
  • The text explores how epigenetic modifications like DNA methylation and histone changes play critical roles in cancer initiation, progression, and adaptation to challenges.
  • Understanding these epigenetic changes is essential because they provide cancer cells with a flexible way to survive and evolve in hostile environments and resist treatment.
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Article Synopsis
  • Men of African descent experience the highest rates of prostate cancer, but the genetic factors behind this have not been thoroughly explored.
  • Researchers analyzed genetic data from nearly 4,000 prostate cancer cases and over 3,500 controls across several African countries to identify specific genetic associations related to the disease.
  • The study found 15 significant genetic associations, including four new ones, highlighting that genetic variation in prostate cancer is influenced by unique African alleles, suggesting that more research in diverse populations is crucial for understanding cancer genetics.
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Background: Peripheral neuropathy can affect balance and increase fall risk. Tai Chi is known to activate neuromuscular systems and may help improve balance and postural control. We conducted a scoping review of clinical studies that evaluated the impact of Tai Chi on balance and related neurobiological outcomes among individuals with peripheral neuropathy.

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Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease.

N Engl J Med

September 2024

From University Hospital Regensburg, Regensburg, Germany (D.W.); Dana-Farber Cancer Institute and Harvard Medical School (C.C.) and Massachusetts General Hospital (Z.D.), Boston, and Syndax Pharmaceuticals, Waltham (V.R., T.O., P.O.) - all in Massachusetts; Fred Hutchinson Cancer Center, Seattle (S.J.L.); Washington University School of Medicine, St. Louis (I.P.); Centre Hospitalier Universitaire Sainte-Justine, Montreal (H.B.), and the University of British Columbia, Vancouver General Hospital, Vancouver (J.W.) - both in Canada; the Medical College of Wisconsin, Milwaukee (M.H., S.C.); Stanford Health Care, Stanford (S.A.), and City of Hope Medical Center, Duarte (A.S.) - both in California; Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBiS), CSIC, Universidad de Sevilla, Seville (J.A.P.-S.), Hospital General Universitario Gregorio Marañón, Instituto de Investigación Biomédica Gregorio Marañón, and Universidad Complutense de Madrid, Madrid (M.K.), and Hospital Universitario Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander (A.B.) - all in Spain; the M.D. Anderson Cancer Center, Houston (A.A.); the James Cancer Hospital and Solove Research Institute and Ohio State University Wexner Medical Center, Columbus (H.C.); Seoul National University College of Internal Medicine, Seoul, South Korea (I.K.); Hôpital Saint-Louis and University Paris Cité, Paris (G.S.); Incyte Corporation, Wilmington, DE (C.T.); and Vanderbilt University Medical Center, Nashville (C.L.K.).

Article Synopsis
  • The study investigates the effectiveness of axatilimab, a CSF1R-blocking antibody, for treating chronic graft-versus-host disease (GVHD) in patients post-hematopoietic stem-cell transplantation.
  • In a phase 2 trial involving 241 participants, different doses of axatilimab were tested, with overall response rates of 74%, 67%, and 50% across three dose groups.
  • Alongside substantial improvement in GVHD symptoms measured by patient-reported outcomes, the most frequent side effects were temporary lab abnormalities linked to the treatment.
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Article Synopsis
  • The study aims to uncover genetic changes linked to prolactinomas, ultimately identifying a mutation (ESR1Y537S) in an aggressive case of this tumor type at Brigham and Women's Hospital.
  • A group of twenty patients was analyzed using advanced sequencing techniques, revealing the ESR1Y537S mutation in a post-menopausal woman, which is known to enhance estrogen receptor activity without needing a hormone trigger.
  • The discovery of this mutation allowed for targeted treatment with elacestrant, in combination with radiotherapy, effectively managing tumor growth and significantly lowering prolactin levels in the patient.
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Article Synopsis
  • * When used in combination with the PD-1 inhibitor pembrolizumab, vibostolimab has demonstrated promising antitumor activity, suggesting its potential as a therapeutic option.
  • * The KEYVIBE program includes nine trials to assess the safety and efficacy of vibostolimab alone and in combination treatments for various advanced cancers, providing valuable insights for future therapies.*
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Importance: Immune checkpoint inhibitors (ICIs) have revolutionized cancer care; however, accompanying immune-related adverse events (irAEs) confer substantial morbidity and occasional mortality. Life-threatening irAEs may require permanent cessation of ICI, even in patients with positive tumor response. Therefore, it is imperative to comprehensively define the spectrum of irAEs to aid individualized decision-making around the initiation of ICI therapy.

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Autoimmune diseases, among the most common disorders of young adults, are mediated by genetic and environmental factors. Although CD4FOXP3 regulatory T cells (T) play a central role in preventing autoimmunity, the molecular mechanism underlying their dysfunction is unknown. Here, we performed comprehensive transcriptomic and epigenomic profiling of T in the autoimmune disease multiple sclerosis (MS) to identify critical transcriptional programs regulating human autoimmunity.

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Progressive decline of the adaptive immune system with increasing age coincides with a sharp increase in cancer incidence. In this study, we set out to understand whether deficits in antitumor immunity with advanced age promote tumor progression and/or drive resistance to immunotherapy. We found that multiple syngeneic cancers grew more rapidly in aged versus young adult mice, driven by dysfunctional CD8+ T-cell responses.

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The MCL1 gene is frequently amplified in cancer and codes for the antiapoptotic protein myeloid cell leukemia 1 (MCL1), which confers resistance to the current standard of care. Therefore, MCL1 is an attractive anticancer target. Here we describe BRD-810 as a potent and selective MCL1 inhibitor and its key design principle of rapid systemic clearance to potentially minimize area under the curve-driven toxicities associated with MCL1 inhibition.

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Background And Objective: Until recently, the standard first-line treatment for advanced urothelial carcinoma (UC) was platinum-based combination chemotherapy followed by avelumab maintenance therapy for patients without progressive disease (PD). For patients with advanced UC who experience PD or recurrence, standard-of-care treatment is pembrolizumab monotherapy based on the phase 3 KEYNOTE-045 study. This post hoc analysis of the KEYNOTE-045 study evaluated the efficacy of pembrolizumab compared with chemotherapy by the best response to prior platinum-based chemotherapy.

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Dual therapeutic targeting of MYC and JUNB transcriptional programs for enhanced anti-myeloma activity.

Blood Cancer J

August 2024

Division of Molecular Oncology and Hematology, Department of Basic and Translational Oncology, Karl Landsteiner University of Health Sciences, Krems an der Donau, Austria.

Article Synopsis
  • Deregulated transcription factors (TFs) like MYC and JUNB are key players in the growth of multiple myeloma (MM) but their specific roles and interactions within tumor cells are not well understood.
  • This study reveals that MYC and JUNB operate through separate transcriptional programs, showing that changes in one do not affect the other, highlighting their independent regulation in MM cells.
  • Targeting both MYC and JUNB simultaneously with new therapeutic strategies improves the effectiveness of treatment and could lead to better outcomes for MM patients.
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Importance: Adjuvant ovarian function suppression (OFS) with oral endocrine therapy improves outcomes for premenopausal patients with hormone receptor-positive (HR+) breast cancer but adds adverse effects. A genomic biomarker for selecting patients most likely to benefit from OFS-based treatment is lacking.

Objective: To assess the predictive and prognostic performance of the Breast Cancer Index (BCI) for OFS benefit in premenopausal women with HR+ breast cancer.

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New promises and challenges in the treatment of advanced non-small-cell lung cancer.

Lancet

August 2024

Center for Thoracic Oncology, Tisch Cancer Institute, Mount Sinai Health System, New York City, NY, USA. Electronic address:

Targeted therapies and immunotherapies have radically improved treatment for advanced non-small-cell lung cancer (NSCLC). Tyrosine kinase inhibitors targeting oncogenic driver mutations continue to evolve over multiple generations to enhance effectiveness and tackle drug resistance. Immune checkpoint inhibitors remain integral for the treatment of NSCLCs that do not have specific actionable genetic mutations.

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Article Synopsis
  • Chemotherapy often leads to side effects that can negatively affect treatment outcomes, while exercise during treatment has shown benefits for physical functioning and mental health, but its impact on clinical outcomes like chemotherapy dose intensity is uncertain.
  • The ENICTO Consortium, funded by the National Cancer Institute, aims to fill this knowledge gap by exploring how exercise and nutrition may improve chemotherapy-related outcomes and detailing distinct research projects within their framework.
  • The findings from ENICTO could change oncology care practices, making exercise and nutrition support a standard part of cancer treatment alongside chemotherapy to enhance overall effectiveness and patient outcomes.
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According to the new WHO classification of 2021, gliomas are a heterogeneous group of tumors with very different histology, molecular genetics, and prognoses. In addition to glioblastomas, the most common gliomas, there are also numerous less common gliomas, some of which have a very favorable prognosis. Targeted radionuclide therapy is a therapeutic option that can be attractive if a tumor can be targeted based on its molecular characteristics.

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Background: Yoga interventions need fidelity monitoring to standardize the trial process and ensure adherence. We examined fidelity measures of current yoga trials and developed a fidelity assurance process in a phase III randomized clinical trial addressing chemotherapy-induced peripheral neuropathy among cancer survivors.

Methods: We qualitatively analyzed the fidelity monitoring components in published clinical trials on yoga therapy for chemotherapy-induced peripheral neuropathy through a literature search in PubMed from inception to February 2023.

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Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer.

Cancer Cell

August 2024

Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

Small cell lung cancers (SCLCs) are composed of heterogeneous subtypes marked by lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. POU2F3-positive SCLCs, ∼12% of all cases, are uniquely dependent on POU2F3 itself; as such, approaches to attenuate POU2F3 expression may represent new therapeutic opportunities. Here using genome-scale screens for regulators of POU2F3 expression and SCLC proliferation, we define mSWI/SNF complexes as top dependencies specific to POU2F3-positive SCLC.

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RANO 2.0 criteria: concepts applicable to the neuroradiologist's clinical practice.

Curr Opin Oncol

November 2024

UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, University of California Los Angeles, Los Angeles, California, USA.

Purpose Of Review: The Response Assessment in Neuro-Oncology (RANO) 2.0 criteria aim at improving the standardization and reliability of treatment response assessment in clinical trials studying central nervous system (CNS) gliomas. This review presents the evidence supporting RANO 2.

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Background: The rationale for ethnic differences in bladder cancer (BCa) susceptibility is an important open question. In this study, we raised the hypothesis that the APOBEC3-rs1014971 variant associated with BCa risk and APOBEC-mutagenesis probably contribute to ethnic differences.

Methods: We calculated the ethnicity-stratified 5-year age-adjusted incidence rates of BCa using the US SEER database.

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Article Synopsis
  • The study investigates the effects of blocking IL1β in combination with PD1 blockade and chemotherapy on myeloid immunosuppression and T-cell responses in patients with advanced pancreatic cancer.
  • Results showed a slight increase in activated CD8+ T cells and a reduction in myeloid-derived suppressor cells (MDSCs) in the blood of trial patients compared to those receiving standard chemotherapy.
  • However, changes in the tumor microenvironment were minimal, suggesting that larger studies are needed to fully understand the impacts of these treatments on tumor immunity.
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