Extracellular vesicles (EVs) transport biomolecules that mediate intercellular communication. We previously showed that EVs contain DNA (EV-DNA) representing the entire genome. However, the mechanism of genomic EV-DNA packaging and its role in cancer remain elusive.
View Article and Find Full Text PDFAfter disease progression on endocrine therapy (ET) plus a CDK4/6 inhibitor, there is no standardized sequence for subsequent treatment lines for estrogen receptor positive (ER+) metastatic breast cancer (MBC). CDK4/6i retrial as a treatment strategy is commonplace in modern clinical practice; however, the available prospective data investigating this strategy have had inconclusive results. To frame this data in a real-world context, we performed a retrospective analysis assessing the efficacy of CDK4/6is in 195 patients who had previous exposure to CDK4/6i in a prior treatment line at our institution.
View Article and Find Full Text PDFBackground: Malignant wounds can present in up to 14.5% of patients with advanced cancer, significantly reducing quality of life (QoL). Management of malignant wounds is generally palliative, with the goal of improving or maintaining QoL.
View Article and Find Full Text PDFBreast Cancer Res Treat
December 2024
While CD40 agonism is an attractive approach for activating antigen-presenting cells and initiating antitumor responses, previous attempts have encountered limited clinical efficacy coupled with toxicity. We previously demonstrated that interactions between the antibody Fc domain and the inhibitory receptor FcγRIIB are critical for enhanced antitumor activity. Here, we present the results of a phase 1 study on intratumoral administration of an anti-CD40 agonistic antibody (2141-V11) Fc-engineered to enhance FcγRIIB binding.
View Article and Find Full Text PDFExtracellular vesicles and particles (EVPs) are pivotal mediators of pre-metastatic niche formation and cancer progression, including induction of vascular permeability, which facilitates tumor cell extravasation and metastasis. However, the mechanisms through which EVPs exert this effect remain poorly understood. Here, we elucidate a novel mechanism by which tumor EVPs enhance endothelial cell permeability, tumor extravasation, and lung metastasis to different degrees, depending on tumor type.
View Article and Find Full Text PDFAfter disease progression on endocrine therapy (ET) plus a CDK4/6 inhibitor, there is no standardized sequence for subsequent treatment lines for estrogen receptor positive (ER+) metastatic breast cancer (MBC). CDK4/6i retrial as a treatment strategy is commonplace in modern clinical practice; however, the available prospective data investigating this strategy have had inconclusive results. To frame this data in a real-world context, we performed a retrospective analysis assessing the efficacy of CDK4/6is in 195 patients who had previous exposure to CDK4/6i in a prior treatment line at our institution.
View Article and Find Full Text PDFRadioimmunoconjugates targeting human epidermal growth factor receptor 2 (HER2) have shown potential to noninvasively visualize HER2-positive tumors. However, the stochastic approach that has been traditionally used to radiolabel these antibodies yields poorly defined and heterogeneous products with suboptimal in vivo performance. Here, we describe a first-in-human PET study on patients with HER2-positive breast cancer evaluating the safety, biodistribution, and dosimetry of Zr-site-specific (ss)-pertuzumab PET, a site-specifically labeled radioimmunoconjugate designed to circumvent the limitations of random stochastic lysine labeling.
View Article and Find Full Text PDFCancer alters the function of multiple organs beyond those targeted by metastasis. Here we show that inflammation, fatty liver and dysregulated metabolism are hallmarks of systemically affected livers in mouse models and in patients with extrahepatic metastasis. We identified tumour-derived extracellular vesicles and particles (EVPs) as crucial mediators of cancer-induced hepatic reprogramming, which could be reversed by reducing tumour EVP secretion via depletion of Rab27a.
View Article and Find Full Text PDFCirculating IL-6, an activator of JAK/STAT signaling, is associated with poor prognosis and aromatase inhibitor (AI) resistance in hormone-receptor positive (HR+) breast cancer. Here we report the results of a phase 2 single-arm Simon 2-stage trial combining Ruxolitinib, an oral selective inhibitor of JAK1/2, with exemestane, a steroidal AI, in patients with HR+ metastatic breast cancer (MBC) after progression on non-steroidal AI (NSAI). Safety and efficacy were primary objectives, and analysis of inflammatory markers as predictors of response was a key secondary objective.
View Article and Find Full Text PDFEstrogen receptor alpha (ERα) drives mammary gland development and breast cancer (BC) growth through an evolutionarily conserved linkage of DNA binding and hormone activation functions. Therapeutic targeting of the hormone binding pocket is a widely utilized and successful strategy for breast cancer prevention and treatment. However, resistance to this endocrine therapy is frequently encountered and may occur through bypass or reactivation of ER-regulated transcriptional programs.
View Article and Find Full Text PDFPurpose: Chemotherapy with or without immunotherapy remains the mainstay of treatment for triple-negative breast cancer (TNBC). A subset of TNBCs express the androgen receptor (AR), representing a potential new therapeutic target. This study assessed the feasibility of adjuvant enzalutamide, an AR antagonist, in early-stage, AR-positive (AR +) TNBC.
View Article and Find Full Text PDFRecent studies suggest that Th2 cells play a key role in the pathology of secondary lymphedema by elaborating cytokines such as IL4 and IL13. The aim of this study was to test the efficacy of QBX258, a monoclonal IL4/IL13 neutralizing antibody, in women with breast cancer-related lymphedema (BCRL). We enrolled nine women with unilateral stage I/II BCRL and treated them once monthly with intravenous infusions of QBX258 for 4 months.
View Article and Find Full Text PDFPurpose: Epichaperome network maintenance is vital to survival of tumors that express it. PU-H71 is an epichaperome inhibitor that binds to the ATP-binding site of HSP90 and has demonstrated antitumor activity in breast cancer xenograft models and clinical safety in patients. PU-positron emission tomography (PET) is a theragnostic imaging tool that allows visualization of the epichaperome target.
View Article and Find Full Text PDFThere is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers.
View Article and Find Full Text PDFPurpose: To describe ablation of bone, liver, lung, and soft tissue tumors from oligometastatic breast cancer and to define predictors of local progression and progression-free survival (PFS).
Materials And Methods: A total of 33 women (mean age 52 ± 12 years old; range, 28-69 years), underwent 46 thermal ablations of liver (n = 35), lung (n = 7), and bone/soft tissue (n = 4) metastases. Mean tumor diameter was 18 ± 15 mm (range, 6-50 mm).
Purpose: Rash develops in approximately 50% of patients receiving alpelisib for breast cancer, often requiring dose modifications. Here, we describe the clinicopathologic, laboratory, and management characteristics of alpelisib-related dermatologic adverse events (dAEs).
Methods: A single center-retrospective analysis was conducted.
The development of effective therapies against brain metastasis is currently hindered by limitations in our understanding of the molecular mechanisms driving it. Here we define the contributions of tumour-secreted exosomes to brain metastatic colonization and demonstrate that pre-conditioning the brain microenvironment with exosomes from brain metastatic cells enhances cancer cell outgrowth. Proteomic analysis identified cell migration-inducing and hyaluronan-binding protein (CEMIP) as elevated in exosomes from brain metastatic but not lung or bone metastatic cells.
View Article and Find Full Text PDFJ Extracell Vesicles
November 2018
Purpose: To describe imaging response and survival after radioembolization for metastatic breast cancer and to delineate genetic predictors of imaging responses and outcomes.
Materials And Methods: This retrospective study included 31 women (average age, 52 y) with liver metastasis from invasive ductal carcinoma who underwent resin and glass radioembolization (average cumulative dose, 2.0 GBq ± 1.
Background: Overexpression and activation of tyrosine kinase Src has been linked to breast carcinogenesis and bone metastases. We showed the feasibility of combining the SRC inhibitor dasatinib with weekly paclitaxel in patients with metastatic breast cancer (MBC) and herein report the subsequent phase II trial.
Patients And Methods: Patients had received ≤ 2 chemotherapy regimens for measurable, HER2-negative MBC.
The heterogeneity of exosomal populations has hindered our understanding of their biogenesis, molecular composition, biodistribution and functions. By employing asymmetric flow field-flow fractionation (AF4), we identified two exosome subpopulations (large exosome vesicles, Exo-L, 90-120 nm; small exosome vesicles, Exo-S, 60-80 nm) and discovered an abundant population of non-membranous nanoparticles termed 'exomeres' (~35 nm). Exomere proteomic profiling revealed an enrichment in metabolic enzymes and hypoxia, microtubule and coagulation proteins as well as specific pathways, such as glycolysis and mTOR signalling.
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