Modeling Drug Responses and Evolutionary Dynamics using Patient-Derived Xenografts Reveals Precision Medicine Strategies for Triple Negative Breast Cancer.

The inter- and intra-tumor heterogeneity of triple negative breast cancers (TNBC), which is reflected in diverse drug responses, interplays with tumor evolution. Here, we developed a preclinical experimental and analytical framework using treatment-naive TNBC patient-derived tumor xenografts (PDTX) to test their predictive value in personalized cancer treatment approaches. Patients and their matched PDTX exhibited concordant drug responses to neoadjuvant therapy using two trial designs and dosing schedules.

Development and validation of a reliable DNA copy-number-based machine learning algorithm (CopyClust) for breast cancer integrative cluster classification.

The Integrative Cluster subtypes (IntClusts) provide a framework for the classification of breast cancer tumors into 10 distinct groups based on copy number and gene expression, each with unique biological drivers of disease and clinical prognoses. Gene expression data is often lacking, and accurate classification of samples into IntClusts with copy number data alone is essential. Current classification methods achieve low accuracy when gene expression data are absent, warranting the development of new approaches to IntClust classification.

Predictability of B cell clonal persistence and immunosurveillance in breast cancer.

B cells and T cells are important components of the adaptive immune system and mediate anticancer immunity. The T cell landscape in cancer is well characterized, but the contribution of B cells to anticancer immunosurveillance is less well explored. Here we show an integrative analysis of the B cell and T cell receptor repertoire from individuals with metastatic breast cancer and individuals with early breast cancer during neoadjuvant therapy.

Clustering of HR + /HER2- breast cancer in an Asian cohort is driven by immune phenotypes.

Breast cancer exhibits significant heterogeneity, manifesting in various subtypes that are critical in guiding treatment decisions. This study aimed to investigate the existence of distinct subtypes of breast cancer within the Asian population, by analysing the transcriptomic profiles of 934 breast cancer patients from a Malaysian cohort. Our findings reveal that the HR + /HER2- breast cancer samples display a distinct clustering pattern based on immune phenotypes, rather than conforming to the conventional luminal A-luminal B paradigm previously reported in breast cancers from women of European descent.

ψ(2S) Suppression in Pb-Pb Collisions at the LHC.

The production of the ψ(2S) charmonium state was measured with ALICE in Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV, in the dimuon decay channel. A significant signal was observed for the first time at LHC energies down to zero transverse momentum, at forward rapidity (2.

Vitamin B supports MYC oncogenic metabolism and tumor progression in breast cancer.

Tumors are intrinsically heterogeneous and it is well established that this directs their evolution, hinders their classification and frustrates therapy. Consequently, spatially resolved omics-level analyses are gaining traction. Despite considerable therapeutic interest, tumor metabolism has been lagging behind this development and there is a paucity of data regarding its spatial organization.

Measurement of the Lifetime and Λ Separation Energy of _{Λ}^{3}H.

The most precise measurements to date of the _{Λ}^{3}H lifetime τ and Λ separation energy B_{Λ} are obtained using the data sample of Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV collected by ALICE at the LHC. The _{Λ}^{3}H is reconstructed via its charged two-body mesonic decay channel (_{Λ}^{3}H→^{3}He+π^{-} and the charge-conjugate process).

Enhanced Deuteron Coalescence Probability in Jets.

The transverse-momentum (p_{T}) spectra and coalescence parameters B_{2} of (anti)deuterons are measured in p-p collisions at sqrt[s]=13  TeV for the first time in and out of jets. In this measurement, the direction of the leading particle with the highest p_{T} in the event (p_{T}^{lead}>5  GeV/c) is used as an approximation for the jet axis. The event is consequently divided into three azimuthal regions, and the jet signal is obtained as the difference between the toward region, that contains jet fragmentation products in addition to the underlying event (UE), and the transverse region, which is dominated by the UE.

Measurement of the J/ψ Polarization with Respect to the Event Plane in Pb-Pb Collisions at the LHC.

We study the polarization of inclusive J/ψ produced in Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV at the LHC in the dimuon channel, via the measurement of the angular distribution of its decay products. We perform the study in the rapidity region 2.

Comparison of tumor-informed and tumor-naïve sequencing assays for ctDNA detection in breast cancer.

Analysis of circulating tumor DNA (ctDNA) to monitor cancer dynamics and detect minimal residual disease has been an area of increasing interest. Multiple methods have been proposed but few studies have compared the performance of different approaches. Here, we compare detection of ctDNA in serial plasma samples from patients with breast cancer using different tumor-informed and tumor-naïve assays designed to detect structural variants (SVs), single nucleotide variants (SNVs), and/or somatic copy-number aberrations, by multiplex PCR, hybrid capture, and different depths of whole-genome sequencing.

Evaluation and comparison of different breast cancer prognosis scores based on gene expression data.

Background: Breast cancer is one of the three most common cancers worldwide and is the most common malignancy in women. Treatment approaches for breast cancer are diverse and varied. Clinicians must balance risks and benefits when deciding treatments, and models have been developed to support this decision-making.

Copy number heterogeneity identifies ER+ breast cancer patients that do not benefit from adjuvant endocrine therapy.

Background: Endocrine therapy forms the backbone of adjuvant treatment for oestrogen-receptor-positive (ER+) breast cancer. However, it remains unclear whether adjuvant treatment improves survival rates in low-risk patients. Low intra-tumour heterogeneity (ITH) has been shown to confer low risk for recurrent disease.

Hypertriton Production in p-Pb Collisions at sqrt[s_{NN}]=5.02 TeV.

The study of nuclei and antinuclei production has proven to be a powerful tool to investigate the formation mechanism of loosely bound states in high-energy hadronic collisions. The first measurement of the production of _{Λ}^{3}H in p-Pb collisions at sqrt[s_{NN}]=5.02  TeV is presented in this Letter.

Polarization of Λ and Λ[over ¯] Hyperons along the Beam Direction in Pb-Pb Collisions at sqrt[s]_{NN}=5.02 TeV.

The polarization of the Λ and Λ[over ¯] hyperons along the beam (z) direction, P_{z}, has been measured in Pb-Pb collisions at sqrt[s_{NN}]=5.02  TeV recorded with ALICE at the Large Hadron Collider (LHC). The main contribution to P_{z} comes from elliptic flow-induced vorticity and can be characterized by the second Fourier sine coefficient P_{z,s2}=⟨P_{z}sin(2φ-2Ψ_{2})⟩, where φ is the hyperon azimuthal emission angle and Ψ_{2} is the elliptic flow plane angle.

Breast tumor microenvironment structures are associated with genomic features and clinical outcome.

The functions of the tumor microenvironment (TME) are orchestrated by precise spatial organization of specialized cells, yet little is known about the multicellular structures that form within the TME. Here we systematically mapped TME structures in situ using imaging mass cytometry and multitiered spatial analysis of 693 breast tumors linked to genomic and clinical data. We identified ten recurrent TME structures that varied by vascular content, stromal quiescence versus activation, and leukocyte composition.

Nucleoporin-93 reveals a common feature of aggressive breast cancers: robust nucleocytoplasmic transport of transcription factors.

By establishing multi-omics pipelines, we uncover overexpression and gene copy-number alterations of nucleoporin-93 (NUP93), a nuclear pore component, in aggressive human mammary tumors. NUP93 overexpression enhances transendothelial migration and matrix invasion in vitro, along with tumor growth and metastasis in animal models. These findings are supported by analyses of two sets of naturally occurring mutations: rare oncogenic mutations and inactivating familial nephrotic syndrome mutations.

Measurement of Prompt D^{0}, Λ_{c}^{+}, and Σ_{c}^{0,++}(2455) Production in Proton-Proton Collisions at sqrt[s]=13 TeV.

The p_{T}-differential production cross sections of prompt D^{0}, Λ_{c}^{+}, and Σ_{c}^{0,++}(2455) charmed hadrons are measured at midrapidity (|y|<0.5) in pp collisions at sqrt[s]=13  TeV. This is the first measurement of Σ_{c}^{0,++} production in hadronic collisions.

Measurement of the Cross Sections of Ξ_{c}^{0} and Ξ_{c}^{+} Baryons and of the Branching-Fraction Ratio BR(Ξ_{c}^{0}→Ξ^{-}e^{+}ν_{e})/BR(Ξ_{c}^{0}→Ξ^{-}π^{+}) in pp Collisions at sqrt[s]=13 TeV.

The p_{T}-differential cross sections of prompt charm-strange baryons Ξ_{c}^{0} and Ξ_{c}^{+} were measured at midrapidity (|y|<0.5) in proton-proton (pp) collisions at a center-of-mass energy sqrt[s]=13  TeV with the ALICE detector at the LHC. The Ξ_{c}^{0} baryon was reconstructed via both the semileptonic decay (Ξ^{-}e^{+}ν_{e}) and the hadronic decay (Ξ^{-}π^{+}) channels.

Multi-omic machine learning predictor of breast cancer therapy response.

Breast cancers are complex ecosystems of malignant cells and the tumour microenvironment. The composition of these tumour ecosystems and interactions within them contribute to responses to cytotoxic therapy. Efforts to build response predictors have not incorporated this knowledge.

Λ_{c}^{+} Production and Baryon-to-Meson Ratios in pp and p-Pb Collisions at sqrt[s_{NN}]=5.02 TeV at the LHC.

The prompt production of the charm baryon Λ_{c}^{+} and the Λ_{c}^{+}/D^{0} production ratios were measured at midrapidity with the ALICE detector in pp and p-Pb collisions at sqrt[s_{NN}]=5.02  TeV. These new measurements show a clear decrease of the Λ_{c}^{+}/D^{0} ratio with increasing transverse momentum (p_{T}) in both collision systems in the range 2 View Article and Find Full Text PDF

Positive correlation between transcriptomic stemness and PI3K/AKT/mTOR signaling scores in breast cancer, and a counterintuitive relationship with PIK3CA genotype.

A PI3Kα-selective inhibitor has recently been approved for use in breast tumors harboring mutations in PIK3CA, the gene encoding p110α. Preclinical studies have suggested that the PI3K/AKT/mTOR signaling pathway influences stemness, a dedifferentiation-related cellular phenotype associated with aggressive cancer. However, to date, no direct evidence for such a correlation has been demonstrated in human tumors.