Monitoring changing patterns in HER2 addiction by liquid biopsy in advanced breast cancer patients.

Background: During targeted treatment, HER2-positive breast cancers invariably lose HER2 DNA amplification. In contrast, and interestingly, HER2 proteins may be either lost or gained. To longitudinally and systematically appreciate complex/discordant changes in HER2 DNA/protein stoichiometry, HER2 DNA copy numbers and soluble blood proteins (aHER2/sHER2) were tested in parallel, non-invasively (by liquid biopsy), and in two-dimensions, hence HER2-2D.

Combined TP53 status in tumor-free resection margins and circulating microRNA profiling predicts the risk of locoregional recurrence in head and neck cancer.

Locoregional recurrences represent a frequently unexpected problem in head and neck squamous cell carcinoma (HNSCC). Relapse often (10-30%) occurs in patients with histologically negative resection margins (RMs), probably due to residual tumor cells or hidden pre-cancerous lesions in normal mucosa, both missed by histopathological examination. Therefore, definition of a 'clean' or tumor-negative RM is controversial, demanding for novel approaches to be accurately explored.

Immunosignatures associated with TP53 status and co-mutations classify prognostically head and neck cancer patients.

Background: 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.

Methods: We analyzed the TCGA cohort of HNSCC patients in relation to their activation of 26 immune gene expression signatures, as well as their cell type composition, in order to define signaling pathways associated with resistance to ICIs.

Direct competitive assay for HER2 detection in human plasma using Bloch surface wave-based biosensors.

The overexpression and/or amplification of the HER2/neu oncogene has been proposed as a prognostic marker in breast cancer. The detection of the related peptide HER2 remains a grand challenge in cancer diagnosis and for therapeutic decision-making. Here, we used a biosensing device based on Bloch Surface Waves excited on a one-dimensional photonic crystal (1DPC) as valid alternative to standard techniques.

The Molecular Tumor Board of the Regina Elena National Cancer Institute: from accrual to treatment in real-world.

Background: Molecular Tumor Boards (MTB) operating in real-world have generated limited consensus on good practices for accrual, actionable alteration mapping, and outcome metrics. These topics are addressed herein in 124 MTB patients, all real-world accrued at progression, and lacking approved therapy options.

Methods: Actionable genomic alterations identified by tumor DNA (tDNA) and circulating tumor DNA (ctDNA) profiling were mapped by customized OncoKB criteria to reflect diagnostic/therapeutic indications as approved in Europe.

Unusual phylogenetic tree and circulating actionable ESR1 mutations in an aggressive luminal/HER2-low breast cancer: Case report.

Under therapeutic pressure aggressive tumors evolve rapidly. Herein, a luminal B/HER2-low breast cancer was tracked for >3 years during a total of 6 largely unsuccessful therapy lines, from adjuvant to advanced settings. Targeted next generation sequencing (NGS) of the primary lesion, two metastases and 14 blood drawings suggested a striking, unprecedented coexistence of three evolution modes: punctuated, branched and convergent.

Overexpression in metastatic breast cancer supports Syndecan-1 as a marker of invasiveness and poor prognosis.

Background: Metastasis is the main cause of breast cancer (BC) mortality. Increasing evidence points to a role of syndecan-1 (CD138) expression as a prognostic marker involved in BC tissue and leptomeningeal metastasis. Aim of this study was to investigate and compare syndecan-1 tissue expression and localization in primary and secondary BC, focusing on brain metastases.

Nuclear pores dilate and constrict in cellulo.

In eukaryotic cells, nuclear pore complexes (NPCs) fuse the inner and outer nuclear membranes and mediate nucleocytoplasmic exchange. They are made of 30 different nucleoporins and form a cylindrical architecture around an aqueous central channel. This architecture is highly dynamic in space and time.

[Corrigendum] TOOLBOX: Strep‑Tagged nano‑assemblies of antibody‑drug‑conjugates (ADC) for modular and conditional cancer drugging.

Following the publication of the above article, the authors have requested a change in the authorship on the paper, and the revised list of authors is presented above; essentially, the ninth intended author, Giuseppe Salvo (G.S.), was inadverently omitted from the author list.

TOOLBOX: Strep‑Tagged nano‑assemblies of antibody‑drug‑conjugates (ADC) for modular and conditional cancer drugging.

Herein, we describe TOOLBOX, a 3‑step modular nano‑assembly targeting system that permits the combinatorial exchange of antibody specificities and toxic payloads, introducing modularity in antibody‑drug conjugate (ADC) manufacturing. TOOLBOX integrates 3 building blocks: i) a recombinant antibody fragment (that in the selected setting targets the proto‑oncogene ERBB2) genetically fused to an 8 amino acid Strep‑Tag; ii) a multivalent protein adapter, called Strep‑Tactin; iii) two anticancer agents, e.g.

Detection of Tumor DNA in Human Plasma with a Functional PLL-Based Surface Layer and Plasmonic Biosensing.

Standard protocols for the analysis of circulating tumor DNA (ctDNA) include the isolation of DNA from the patient's plasma and its amplification and analysis in buffered solutions. The application of such protocols is hampered by several factors, including the complexity and time-constrained preanalytical procedures, risks for sample contamination, extended analysis time, and assay costs. A recently introduced nanoparticle-enhanced surface plasmon resonance imaging-based assay has been shown to simplify procedures for the direct detection of tumor DNA in the patient's plasma, greatly simplifying the cumbersome preanalytical phase.

Cone-shaped HIV-1 capsids are transported through intact nuclear pores.

Human immunodeficiency virus (HIV-1) remains a major health threat. Viral capsid uncoating and nuclear import of the viral genome are critical for productive infection. The size of the HIV-1 capsid is generally believed to exceed the diameter of the nuclear pore complex (NPC), indicating that capsid uncoating has to occur prior to nuclear import.

Direct plasmonic detection of circulating RAS mutated DNA in colorectal cancer patients.

RAS mutations in the blood of colorectal cancer (CRC) patients are emerging as biomarkers of acquired resistance to Epidermal Growth Factor Receptor therapy. Unfortunately, reliable assays granting fast, real-time monitoring of treatment response, capable of refining retrospective, tissue-based analysis, are still needed. Recently, several methods for detecting blood RAS mutations have been proposed, generally relying on multi-step and PCR-based, time-consuming and cost-ineffective procedures.

In-cell architecture of the nuclear pore and snapshots of its turnover.

Nuclear pore complexes (NPCs) fuse the inner and outer membranes of the nuclear envelope. They comprise hundreds of nucleoporins (Nups) that assemble into multiple subcomplexes and form large central channels for nucleocytoplasmic exchange. How this architecture facilitates messenger RNA export, NPC biogenesis and turnover remains poorly understood.

A Distinctive microRNA (miRNA) Signature in the Blood of Colorectal Cancer (CRC) Patients at Surgery.

Background: Liquid biopsy (LB) provides an examination of the peripheral blood of cancer patients for circulating tumor cells, cell-free nucleic acids and microRNAs (miRNAs) and is an established tool of precision medicine. Unlike most previous LB studies that focused on advanced metastatic colorectal cancer (CRC), we assessed miRNA dysregulation in blood samples obtained on the day of surgery from patients with primary CRC lesions but no clinical evidence of extra-colonic diffusion. In this study, plasma preparation included miRNAs associated to exosomes, but excluded large macrovesicles from the preparation.

Cryo-EM structures of holo condensin reveal a subunit flip-flop mechanism.

Complexes containing a pair of structural maintenance of chromosomes (SMC) family proteins are fundamental for the three-dimensional (3D) organization of genomes in all domains of life. The eukaryotic SMC complexes cohesin and condensin are thought to fold interphase and mitotic chromosomes, respectively, into large loop domains, although the underlying molecular mechanisms have remained unknown. We used cryo-EM to investigate the nucleotide-driven reaction cycle of condensin from the budding yeast Saccharomyces cerevisiae.

Cross-sectional analysis of circulating tumor DNA in primary colorectal cancer at surgery and during post-surgery follow-up by liquid biopsy.

Background: Liquid biopsy (LB) in early-stage, non-metastatic colorectal cancer (CRC) must be sensitive enough to detect extremely low circulating tumor DNA (ctDNA) levels. This challenge has been seldom and non-systematically investigated.

Methods: Next generation sequencing (NGS) and digital PCR (dPCR) were combined to test tumor DNAs (tDNAs) and paired ctDNAs collected at surgery from 39 patients, 12 of whom were also monitored during the immediate post-surgery follow up.

Bioassay engineering: a combined label-free and fluorescence approach to optimize HER2 detection in complex biological media.

We report on the combined label-free/fluorescence use of one-dimensional photonic crystals to optimize cancer biomarker detection in complex biological media. The optimization of the assay working parameters permits us to maximize the final response of the biosensor. The detection approach utilizes a sandwich assay, in which one-dimensional photonic crystals sustaining Bloch surface waves are modified with monoclonal antibodies in order to guarantee high specificity during biological recognition.

Selective autophagy degrades nuclear pore complexes.

Nuclear pore complexes (NPCs) are very large proteinaceous assemblies that consist of more than 500 individual proteins. NPCs are essential for nucleocytoplasmic transport of different cellular components, and disruption of the integrity of NPCs has been linked to aging, cancer and neurodegenerative diseases. However, the mechanism by which membrane-embedded NPCs are turned over is currently unknown.

An ESCRT-LEM protein surveillance system is poised to directly monitor the nuclear envelope and nuclear transport system.

The integrity of the nuclear membranes coupled to the selective barrier of nuclear pore complexes (NPCs) are essential for the segregation of nucleoplasm and cytoplasm. Mechanical membrane disruption or perturbation to NPC assembly triggers an ESCRT-dependent surveillance system that seals nuclear pores: how these pores are sensed and sealed is ill defined. Using a budding yeast model, we show that the ESCRT Chm7 and the integral inner nuclear membrane (INM) protein Heh1 are spatially segregated by nuclear transport, with Chm7 being actively exported by Xpo1/Crm1.