Cancer Research

Abstract TRPV6, a calcium channel, is an oncochannel that is overexpressed in epithelial cancers, especially prostate cancer. We have observed that concomitant TRPV6 and AR inhibition is synergistic in prostate cancer cells resulting in a strong anti-proliferative effect. Our preclinical candidate QED-203 inhibits TRPV6-mediated calcium influx (FLIPR and electrophysiology) and NFAT activity (NFAT…

Abstract Background: Coordinated metabolic alterations and epigenetic remodeling are known to critically influence T cell fate decisions and functional states. However, the specific extrinsic metabolic signals that guide CD8+ T cell memory differentiation remain to be fully elucidated. Methods: Naïve CD45.1+ OT-I CD8+ T cells were adoptively transferred into Listeria monocytogenes-infected CD45.2…

Abstract Background: The Gambia, the smallest country within mainland Africa, is estimated to have one of the lowest cancer survival rates of countries in Africa, Asia, and Central America. Although poor access to healthcare contributes to low breast cancer survival rates in The Gambia, little is known about patient experiences across multiple healthcare access domains. The purpose of this study …

Abstract Prostate cancer (PCa) is the most common malignancy among men in developed countries, and its increasing incidence is closely associated with the rising prevalence of obesity and metabolic syndrome. Our previous studies demonstrated that the Tanshinone analog (TA) enhances ATF3 expression, inhibits adipogenesis and lipogenesis, and promotes adipocyte browning. Although both native Tanshi…

Abstract Septins are a conserved family of GTP-binding cytoskeletal proteins which form oligomeric filamentous structures that play important roles in a wide variety of dynamic cellular processes, including cytokinesis, membrane remodeling and cell migration. Expression of Septins is dysregulated in different tumors, with some isoforms being either upregulated or downregulated, and prior evidence…

Abstract Background: MiPEP133 is a microprotein encoded by the miR-34a precursor. In normal cells, it functions as a tumor suppressor and is expressed in colon, stomach, ovary, uterus, and pharynx, but its levels are markedly reduced in cancer. Localized in the mitochondria, miPEP133 regulates mitochondrial homeostasis through interactions with mitochondrial chaperones and has been reported to in…

Abstract B7-H3 (B7 homolog 3 protein), also known as CD276 (cluster of differentiation 276), is a cell surface protein that is over-expressed across multiple solid tumors. B7-H3 suppresses T-cell function (e.g. proliferation, activation, and cytokine release) to promote tumorigenesis. Due to its tumor-promoting functions and broad expression profile on a range of malignancies, B7-H3 is an attract…

Abstract Even though most women with estrogen receptor positive (ER+) breast tumors can benefit from endocrine therapy (ET), up to 40% of these patients will eventually experience relapse. Moreover, when these tumors recur, they tend to be more metastatic and therapy-resistant, resulting in disease progression and fatalities. One contributing factor to ET failure and recurrence is intratumoral he…

Abstract Tumor-associated macrophages (TAMs) are considered key determinants of breast cancer progression, yet the molecular mechanisms shaping their immunosuppressive phenotypes remain incompletely understood. The NOX2 enzyme of myeloid cells generates antimicrobial reactive oxygen species (ROS) in myeloid cells, but its potential contribution to macrophage programming within the tumor microenvi…

Abstract Desmosomes are specialized adhesive junctions that link adjacent cells and provide structural integrity in tissues exposed to significant mechanical stress, such as the skin and heart. Disruption of the desmosome adhesion complex is observed in a range of different cutaneous syndromes and during tumor progression. Dysregulation of desmosomal proteins has been associated with enhanced can…

Abstract Background & significance — applications HiBiT is an 11-aa tag that complements LgBiT to reconstitute NanoLuc, delivering a bright, linear bioluminescent readout that scales with target protein abundance. Compared with Western blot-centric workflows, endogenous HiBiT knock-ins enable real-time, quantitative kinetics under native regulation, accelerating mechanism confirmation, potenc…

Abstract Background: High-risk neuroblastoma (NBL), driven by MYCN amplification, remains fatal for many children. Our previous work demonstrated that pharmacologic PP2A reactivation decreases NBL in vivo tumor growth through suppression of MYCN expression and stability by reducing MYCN phosphorylation and promoter acetylation, concurrent with BRD4 and RNA Pol II dephosphorylation. The current st…

Abstract Cancer therapeutics such as CAR T, Radioligand , ADC, and Bispecifics are all reliant on targeting cancer-selective surface proteins. A major limitation to these tethered killing strategies is the lack of targets that are exclusively expressed on tumor cells and not healthy tissues. Most cancer surface targets exhibit “lineage” expression properties, in which expression is shared by both…

Abstract Chromosome 8 (chr8) gain, particularly the gain of its long arm 8q, represents one of the most frequent chromosomal abnormalities across multiple human cancers. In Ewing sarcoma, approximately 50% of cases exhibit chr8 gain while in prostate cancer, high level amplification of 8q occurs in about 24% of primary cases with much higher frequencies in metastatic cases. Across both diseases, …

Abstract Background: Spatial transcriptomics (ST) technology maps gene expression within tissue structures, offering unprecedented insights into tissue organization and cellular interactions. Analyzing these complex datasets, however, remains a significant bottleneck. Current workflows demand specialized, multi-domain expertise and rely on heavy manual intervention, an expertise barrier that hind…

Abstract Clear-cell renal-cell carcinoma (ccRCC) accounts for 70-80% of kidney cancers, with increasing incidence driven by improved imaging, aging populations, and rising obesity rates. No routine diagnostic tests currently predict which small renal masses will progress to large, aggressive tumors, leaving a fundamental clinical question unresolved: do lethal tumors arise with inherently aggress…

Abstract Mesothelioma is a highly aggressive malignancy of the serosal membranes. Alterations in regulatory mechanisms controlling tumor suppressor gene expression play a critical role in Mesothelioma and other malignancies. Although tumor suppressor genes are central to cancer biology, the upstream regulation networks governing their activity remain poorly defined. Here, we identify a novel mole…

Abstract Background: Conventional IgG-based antibody-drug conjugates (ADCs) face major limitations, including heterogeneous drug-to-antibody ratios (DAR), variable pharmacokinetics, limited tumor penetration, and linker instability that can lead to off-target toxicity. To overcome these challenges, Sonnet has developed a non-IgG peptide drug conjugate (PDC) platform that enables precise drug load…

Abstract Purpose: Tissue-of-origin prediction and tumor subtyping enable more precise treatment selection, especially for cancers of unknown primary (CUP) or without a defined subtype, though these remain a challenge in liquid biopsy applications. Current genomic approaches include methylation profiling or whole-genome sequencing, which require additional laboratory workflows on top of comprehens…

Abstract Background: Progressive immune remodeling is a hallmark of early lung adenocarcinoma (LUAD) evolution, yet the integrated transcriptional and clonal trajectories underlying this process remain poorly defined. Methods: Single-cell RNA sequencing (scRNA-seq) data from GSE189357 and HDAC000630 were analyzed across 33 lung samples, spanning normal to invasive adenocarcinoma. After quality co…