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Background Concurrent chemoradiotherapy has been the standard of care for locally advanced cervical cancer for over 20 years; however, 30–40% of treated patients have recurrence or progression within 5 years. Immune checkpoint inhibition has improved outcomes for patients with PD-L1 positive metastatic or recurrent cervical cancer. We assessed the benefit of adding durvalumab, a PD-L1 antibody, with

Background Stereotactic body radiotherapy (SBRT) has the potential to ablate localised pancreatic ductal adenocarcinoma. Selective dismutase mimetics sensitise tumours while reducing normal tissue toxicity. This trial was designed to establish the efficacy and toxicity afforded by the selective dismutase mimetic avasopasem manganese when combined with ablative SBRT for localised pancreatic ductal adenocarcinoma

Background Systemic therapies have improved the management of hepatocellular carcinoma, but there is still a need to further enhance overall survival in first-line advanced stages. This study aimed to evaluate the addition of pembrolizumab to lenvatinib versus lenvatinib plus placebo in the first-line setting for unresectable hepatocellular carcinoma. Methods In this global, randomised, double-blind

Recent clinical trials for H3K27-altered diffuse midline gliomas (DMGs) have shown much promise. We present a consensus roadmap and identify three major barriers: (1) refinement of experimental models to include immune and brain-specific components; (2) collaboration among researchers, clinicians, and industry to integrate patient-derived data through sharing, transparency, and regulatory considerations;

Enzymes that produce metabolites specifically required by cancer cells have become attractive targets for therapy. Recently, Doshi et al. highlighted the potential of targeting the detoxifying enzyme UXS1 in cancer.

Current research has demonstrated that extracellular vesicles (EVs) and circulating tumor cells (CTCs) are very closely related in the process of distant tumor metastasis. Primary tumors are shed and released into the bloodstream to form CTCs that are referred to as seeds to colonize and grow in soil-like distant target organs, while EVs of tumor and nontumor origin act as fertilizers in the process

Immune checkpoint inhibitors (ICIs) are a therapeutic strategy for various cancers although only a subset of patients respond to the therapy. Identifying patients more prone to respond to ICIs may increase the therapeutic benefit and allow studying new approaches for resistant patients. We analyzed the TCGA cohort of HNSCC patients in relation to their activation of 26 immune gene expression signatures

Despite major improvements in immunotherapeutic strategies, the immunosuppressive tumor microenvironment remains a major obstacle for the induction of efficient antitumor responses. In this study, we show that local delivery of a bispecific Clec9A-PD-L1 targeted type I interferon (AcTaferon, AFN) overcomes this hurdle by reshaping the tumor immune landscape. Treatment with the bispecific AFN resulted

Background Incorporating immune checkpoint blockade into perioperative cancer therapy has improved clinical outcomes. However, the safety of immune checkpoint blockade needs better evaluation, given the chances of more prolonged disease-free survival. We aimed to assess how adding immune checkpoint blockade to perioperative therapy affects treatment-related adverse events. Methods For this systematic

Triple-negative breast cancer (TNBC) is an aggressive subtype that exhibits a high incidence of distant metastases and lacks targeted therapeutic options. Here we explored how the epigenome contributes to matrix metalloprotease (MMP) dysregulation impacting tumor invasion, which is the first step of the metastatic process. We combined RNA expression and chromatin interaction data to identify insulator

The advent of iPSCs has brought about a significant transformation in stem cell research, opening up promising avenues for advancing cancer treatment. The formation of cancer is a multifaceted process influenced by genetic, epigenetic, and environmental factors. iPSCs offer a distinctive platform for investigating the origin of cancer, paving the way for novel approaches to cancer treatment, drug testing

The University of Kansas Cancer Center is a National Cancer Institute-designated comprehensive cancer center. It is the only such designated cancer center in the state of Kansas. The cancer center’s mission, through its innovative approach to drug discovery, delivery, and development, is to transform cancer research and clinical care delivered in Kansas and western Missouri. KU Cancer Center operates

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Microsatellite instability (MSI) is a tumor molecular phenotype that evolves from loss of function in the mismatch repair proteins through deleterious germline mutations, epigenetic inactivation or somatic bi-allelic mutations. This phenotype is characterized by genomic hyper-mutability, increased neoantigen expression, and a favorable, immune-rich tumor microenvironment (TME). These features confer

In a recent study published in Cancer Discovery, Hsu and colleagues employ an elegant combination of single-cell and bulk RNA-seq experiments from mouse and human colorectal cancer (CRC) samples, patient-derived organoids, 2D in vitro systems, and in vivo validation in genetically engineered CRC mouse models to investigate how mutant KRAS (KRAS*) impacts the tumor microenvironment. They identify a

Inherited germline and acquired somatic alterations can both promote human tumor development. Elucidating the cooperation between somatic and germline genetic alterations that drive tumorigenesis could help inform precision cancer prevention and treatment strategies. Here, leveraging genomic genotyping and sequencing data from 9,029 cancer patients with European, East Asian, and African ancestry, we

Background Studies of sleep and prostate cancer are almost entirely based on self-report, with limited research using actigraphy. Our goal was to evaluate actigraphy-measured sleep and prostate cancer and to expand on findings from prior studies of self-reported sleep. Methods We prospectively examined 34 260 men without a history of prostate cancer in the UK Biobank. Sleep characteristics were measured

Immunotherapies have revolutionized the treatment paradigms of various types of cancers. However, most of these immunomodulatory strategies focus on harnessing adaptive immunity, mainly by inhibiting immunosuppressive signaling with immune checkpoint blockade, or enhancing immunostimulatory signaling with bispecific T cell engager and chimeric antigen receptor (CAR)-T cell. Although these agents have

On May 25th, 2022, FDA approved a supplemental application for ivosidenib (Tibsovo; Servier) extending the indication in patients with newly-diagnosed IDH1-mutated acute myeloid leukemia (AML) in older adults or those with comorbidities to include the combination with azacitidine. The efficacy of ivosidenib in combination with azacitidine was evaluated in Study AG120-C-009, a phase 3, multicenter,

Purpose: Anastomotic leak (AL) is a major complication in colorectal cancer (CRC) surgery, and consists of the leakage of intestinal content through a poorly healed colonic wound. CRC recurrence after surgery is a major determinant of survival. We hypothesize that AL may allow cancer cells to escape the gut and lead to cancer recurrence, and that improving anastomotic healing may prevent local implantation

Background While animal experiments suggest beneficial effects of physical activity (PA) on anti-tumor immunity, little is known about the effects of PA on immune checkpoint inhibitor (ICI) toxicity and effectiveness in humans. We assessed the association of PA with immune-related adverse events (irAE) and survival in patients undergoing ICI. Methods Patients receiving ICI who completed the PA-SQUASH

Recent studies have uncovered various physiological functions of CDK5 in many nonneuronal tissues. Upregulation of CDK5 and/or its activator p35 in neurons promotes healthy neuronal functions, but their overexpression in nonneuronal tissues is causally linked to cancer of many origins. This review focuses on the molecular mechanisms by which CDK5 recruits diverse tissue-specific substrates to elicit

Vulnerable populations remain disproportionately at risk for inferior childhood cancer outcomes. Here, I outline the scope and magnitude of childhood cancer disparities worldwide and suggest multi-level clinical care and research opportunities to address cancer health inequities. Although childhood cancer survival rates have increased globally, there is a markedly inequitable distribution of these

New trial data confirm the potential of tertiary lymphoid structures to serve as a predictive biomarker of responsiveness to an immune checkpoint inhibitor–based drug regimen. According to study results presented at the Society for Immunotherapy of Cancer Annual Meeting, treatment with a PD-L1–targeted agent plus a multikinase inhibitor with anti-angiogenic activity yielded clinical responses in patients

Purpose: Endocrine-based therapy is the initial primary treatment option for HR+/HER2− mBC. However, patients eventually experience disease progression due to resistance to endocrine therapy. Molibresib (GSK525762) is a small-molecule inhibitor of BET family proteins (BRD2, BRD3, BRD4, and BRDT). Pre-clinical data suggested that the combination of molibresib with endocrine therapy might overcome endocrine

Purpose: Myeloproliferative neoplasms (MPN) dysregulate JAK2 signaling. Since clinical JAK2 inhibitors have limited disease-modifying effects, type II JAK2 inhibitors such as CHZ868 stabilizing inactive JAK2 and reducing MPN clones, gain interest. We studied whether MPN cells escape from type ll inhibition. Methods: MPN cells were continuously exposed to CHZ868. We used phosphoproteomic analyses and

Purpose: Combination of chemotherapy (CT) with programmed cell death (PD)-1 blockade is a front-line treatment for lung cancer. However, it remains unknown whether and how CT affects the response of exhausted CD8 T cells to PD-1 blockade. Experimental design: We used the well-established mouse model of T cell exhaustion with chronic lymphocytic choriomeningitis virus (LCMV) infection to assess the

Despite the immense success of immune checkpoint blockade (ICB) in cancer treatment, many tumors, including melanoma, exhibit innate or adaptive resistance. Tumor-intrinsic T-cell deficiency and T-cell dysfunction have been identified as essential factors in the emergence of ICB resistance. Here, we found that protein arginine methyl transferase 1 (PRMT1) expression was inversely correlated with the

Aberrant gene expression is a prominent feature of metastatic cancer. Translational initiation is a vital step in fine-tuning gene expression. Thus, exploring translation initiation regulators may identify therapeutic targets for preventing and treating metastasis. Herein, we identified that DHCR24 was overexpressed in lymph node (LN) metastatic bladder cancer (BCa) and correlated with poor prognosis

Although incarcerated adults are at elevated risk of dying from cancer, little is known about cancer screening in carceral settings. This study compared stage-specific incidence of screen-detectable cancers among incarcerated and recently released people with the general population, as a reflection of screening practices. We calculated the age- and sex-standardized incidence ratios (SIR) for early-

Vanderbilt University Medical Center's W. Kimryn Rathmell, MD, PhD, MMHC, will serve as the 17th director of the NCI, bringing her extensive research experience, clinical proficiency, institutional leadership, and a commitment to mentorship to the position.

When the cyclin kinase 4/6 inhibitor abemaciclib was sequenced with PD-1 blockade in mostly immunologically “cold” murine models, enhanced immune-mediated antitumor effects—including increased lifespan, recruitment of CD8 cells to tumor, reduction of Treg and immunosuppressive cytokines in tumor, increased tumor antigen presentation, and broadening of the TCR repertoire—were achieved in both cutaneous

MYC is a central regulator of gene transcription and is frequently dysregulated in human cancers. As targeting MYC directly is challenging, an alternative strategy is to identify specific proteins or processes required for MYC to function as a potent cancer driver that can be targeted to result in synthetic lethality. To identify potential targets in MYC-driven cancers, we performed a genome-wide CRISPR

Fulvestrant is used to treat patients with hormone receptor positive advanced breast cancer but acquired resistance is poorly understood. PlasmaMATCH Cohort A (NCT03182634) investigated the activity of fulvestrant in patients with activating ESR1 mutations in circulating tumor DNA (ctDNA). Baseline ESR1 mutations Y537S associated with poor, and Y537C with good outcome. Sequencing of baseline and EOT

In this CCR Translations, we discuss pharmacological ascorbate as a novel therapeutic for glioblastoma. Aberrant iron metabolism in glioblastoma can be assessed noninvasively by MRI and exploited to potentially improve the efficacy of chemoradiotherapy. We contextualize the study’s results and discuss the next steps to further develop this paradigm.

Purpose: Palbociclib, a CDK4/6 inhibitor, has shown radiosensitizing effects in preclinical studies. There is a strong rationale for adding palbociclib to cetuximab and radiotherapy in LA-HNSCC, especially in p16-negative HNSCC. Patients and Methods: We conducted a phase I dose escalation study (NCT03024489) using a classical 3+3 design to determine safety, tolerability, and maximum tolerated dose

Purpose: The safety, pharmacokinetics and efficacy of elraglusib, a GSK-3b small molecule inhibitor, as monotherapy or combined with chemotherapy, in patients with relapsed or refractory solid tumors or hematologic malignancies was studied. Patients and Methods: Elraglusib (intravenously twice weekly in three-week cycles) monotherapy dose-escalation was followed by dose-escalation with eight chemotherapy

Purpose: The integrated stress response (ISR) kinase PERK serves as a survival factor for both proliferative and dormant cancer cells. We aim to validate PERK inhibition as a new strategy to specifically eliminate solitary disseminated cancer cells (DCC) in secondary sites that eventually reawake and originate metastasis. Experimental Design: A novel clinical-grade PERK inhibitor (HC4) was tested in

Purpose: Patients with advanced soft-tissue sarcomas (STSs) exhibit a poor prognosis and have few therapeutic options. DNA-dependent protein kinase catalytic subunit (DNA-PK) is a multifunctional serine—threonine protein kinase that plays a crucial role in DNA double-strand damage repair via nonhomologous end joining (NHEJ). Experimental design: To investigate the therapeutic potential of DNA-PK targeting

Purpose: Cachexia is common in patients with advanced cancer and is associated with elevated serum growth differentiation factor 15 (GDF-15) concentrations. This first-in-patient (phase Ib), 24-week study assessed use of ponsegromab, a monoclonal antibody against GDF-15, in adults with advanced cancer, cachexia, and elevated GDF-15 serum concentration. Experimental Design: Participants (n = 10 received

Neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy with pelvic lymphadenectomy is the current standard therapy for cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC). A phase II trial testing treatment intensification by adding the immune-checkpoint inhibitor nivolumab to chemotherapy has yielded promising complete response rates, which suggests

Currently, only limited knowledge is available regarding the phenotypic association between fibroblast growth factor receptor 3 (FGFR3) alterations and the tumor microenvironment (TME) in bladder cancer (BLCA). A multi-omics analysis on 389 BLCA and 35 adjacent normal tissues from a cohort of OMPU-NCC Consortium Japan was retrospectively performed by integrating the whole-exome and RNA-sequence dataset

Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system. Angiogenesis is a main contributing factor for tumorigenesis. E74-like transcription factor 5 (ELF5) has been verified to participate in the progression of different cancers and can regulate angiogenesis. This study was aimed to explore the functions of ELF5 in RCC. Bioinformatics tools were used to predict the expression

Background Intratumor heterogeneity drives disease progression and treatment resistance, which can lead to poor patient outcomes. Here, we present a computational approach for quantification of cancer cell diversity in routine hematoxylin and eosin (H&E)-stained histopathology images. Methods We analyzed publicly available digitized whole slide H&E images for a total of 2000 patients. Four tumor types