Quantum computing (QC) is emerging as a transformative tool for solving complex optimization problems across various fields, including biomedical applications. While classical optimization methods are well-established, they frequently face limitations when applied to complex and large-scale problems in radiotherapy planning.

This study aims to explore the implementation and evaluate the effectiveness of quantum optimization methods, specifically quantum annealing and the quantum approximate optimization algorithm (QAOA), in radiotherapy planning. In particular, we employ an Ising Hamiltonian formulation of the cost function, empirically implementing it on annealing-based quantum hardware and for the first time on circuit-based one.

We formulated a simplified radiotherapy optimization problem and solved it using quantum annealing on a D-Wave quantum annealer. Subsequently, we adapted this optimization problem for the QAOA framework and implemented it on IBM Quantum circuit-model hardware. Comparative analyses were conducted between classical and quantum methods and implementations, highlighting QC's potential advantages and limitations in specific optimization contexts. To demonstrate that the Hamiltonian formulation is valid and practically usable, we first tested it in simplified proof-of-principle examples and then extended it to a more clinically relevant bilateral prostate proton plan. In this new example, dose parameters were extracted directly from a commercial treatment planning system (RayStation) and incorporated into the Hamiltonian optimization workflow. Both one-qubit-per-voxel and two-qubits-per-voxel encodings were evaluated to illustrate scalability. Additionally, we discussed scalability considerations, practical challenges, and future research directions necessary for integrating quantum algorithms into routine clinical radiation therapy practices.

To our knowledge, this study presents the first demonstration of using QC circuit-model hardware for radiotherapy planning optimization. The quantum annealing approach successfully determined the optimal solution. Convergence was achieved after 20 iterations on a quantum simulator (noise free) and after 100 iterations on actual quantum hardware (due to inherent hardware noise). In the bilateral prostate proton plan derived from realistic data, the Hamiltonian-based optimization assigned higher dose to the prostate relative to surrounding organs-at-risk, confirming the feasibility of applying QC optimization directly to clinically sourced parameters.

Quantum optimization techniques demonstrate potential advantages over classical methods, particularly in complex optimization scenarios relevant to radiation therapy. The formulation of a Hamiltonian cost function, its validation on real quantum hardware, and its application to realistic data collectively represent a first concrete step toward QC-based treatment planning optimization in medical physics. Future research should focus on addressing scalability, overcoming practical implementation challenges, and advancing the development of scalable, fault-tolerant quantum systems suitable for clinical integration.

Carbonyl reductase 1 (CBR1), a member of the short-chain dehydrogenase/reductase (SDR) superfamily, is implicated in tumor progression and treatment resistance. However, its role in non-small cell lung cancer (NSCLC) remains unclear. This study examined CBR1 expression in NSCLC tissues and cell lines, using gene interference and pharmacological inhibition to assess its impact on stemness, chemosensitivity, and quiescence, and to explore underlying mechanisms. Our findings indicate that CBR1 expression is elevated in NSCLC tissues and cell lines, and further increases in the presence of cisplatin (CDDP). Gene interference reducing CBR1 expression significantly decreased the percentage of cluster of differentiation 133 (CD133)-positive cells and the expression of octamer-binding transcription factor 4 (OCT4) and SRY (sex determining region Y)-box 2 (SOX2), while enhancing CDDP chemosensitivity. The CBR1-specific inhibitor hydroxy-PP-Me (PP-Me) markedly increased CDDP cytotoxicity and reduced stemness. Additionally, CBR1 inhibition via short hairpin RNA (shRNA) CBR1 (sh-CBR1) or PP-Me disrupted NSCLC cell quiescence, as shown by a decrease in G0 phase cells and p27 expression, alongside an increase in cyclin D1 and phospho-retinoblastoma (pRb) expression. Furthermore, SET domain-containing protein 4 (SETD4), which mediates stemness, chemosensitivity, and quiescence in NSCLC cells, was downregulated by sh-CBR1 or PP-Me treatment. The overexpression of SETD4 counteracted the enhanced chemosensitivity resulting from CBR1 inhibition. In A549 xenografts, combined PP-Me and CDDP therapy significantly inhibited tumor growth compared to either treatment alone. In conclusion, CBR1 inhibition enhances CDDP chemosensitivity by suppressing stemness and quiescence in NSCLC.

To identify pyroptosis, apoptosis, and necroptosis (PANoptosis)-related genes (PRGs) in clear cell renal cell carcinoma (ccRCC) for patient stratification and prognosis prediction.

We used differential expression analysis and weighted gene co-expression network analysis (WGCNA) to identify ccRCC-specific PRGs. A prognostic model, the PANoptosis-index (PANI), was constructed using least absolute shrinkage and selection operator (LASSO) and Cox regression. The PANI model, comprising PRGs, was validated through single-cell RNA-sequencing (scRNA-seq), immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Patient cohorts were categorized into high- and low-PANI groups, and the model's performance was appraised using various metrics. External validation was performed with the E-MTAB-1980 dataset. Functional and gene set enrichment analyses distinguished biological differences between groups. Mutational landscapes and tumor immune microenvironments were compared. Sensitivity to immunotherapy and antineoplastic drugs was also predicted using PANI. The effects of Z-DNA-binding protein 1 (ZBP1) on cell proliferation and migration were assessed by cell counting kit-8 (CCK-8) and Transwell assays.

We identified five PRGs (ZBP1, tumor necrosis factor superfamily protein 14 (TNFSF14), cyclin-dependent kinase inhibitor 3 (CDKN3), parathyroid hormone-like hormone (PTHLH),and heme-oxygenase 1 (HMOX1)) constituting PANI, independently associated with ccRCC patient prognosis. The PANI-based nomogram, integrated with clinical factors, demonstrated high predictive accuracy for prognosis. High-PANI patients exhibited distinct co-mutation patterns in ccRCC driver genes and lower survival probabilities, with an enriched immune-related functional profile, indicating an activated immune environment. These patients also showed increased sensitivity to immunotherapy and antineoplastic drugs. The knockdown of ZBP1, a key PRG in the PANI, significantly reduced ccRCC cell proliferation and migration.

PANI provides precise prognosis and immunotherapy response predictions for ccRCC patients, facilitating individualized treatment strategies.

CSF3 exerts a significant function in the progression of colorectal cancer (CRC). N6-methyladenosine (m6A) modification is now considered the main driving factor of RNA influence for maintaining homeostasis in cancer cells. Nevertheless, how m6A mediates the role of CSF3 and its influence in pathogenesis of CRC is still elusive. After neutrophil isolation from bone marrow, the purity and survival rate of neutrophils were assessed. Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) was employed to construct the CRC mice model. Both loss-of-function and gain-of-function experiments were conducted to explore the influence of CSF3 on NETosis and tumorigenesis of CRC in vitro and in vivo. The purity and survival rate of neutrophils were 88.07% and 94.84%, respectively. Overexpression of CSF3 (oe-CSF3) markedly enhanced NETosis, while CSF3 knockdown (sh-CSF3) suppressed it. Intriguingly, CSF3 expression positively correlated with relaxin-2 (RLN2) levels in CRC cells, and RLN2 supplementation rescued tumorigenesis and NETosis after sh-CSF3 treatment. Mechanistically, fat mass and obesity-associated protein (FTO)-mediated m6A demethylation of CSF3 mRNA suppressed CRC tumorigenesis in vivo. CSF3 upregulation counteracted the tumor-suppressive effects of FTO overexpression, restoring NETosis and tumor growth. Consistent with this, FTO overexpression in CRC mice alleviated disease severity, as evidenced by improved body weight, reduced tumor burden, and diminished NETosis. Collectively, our findings establish a novel regulatory axis in which FTO-dependent m6A demethylation of CSF3 suppresses NETosis by inhibiting RLN2 expression, offering new insights into therapeutic targeting of the m6A-CSF3-RLN2 pathway in CRC.

circRNAs play pivotal roles in cancer initiation and progression. To explore the metastasis-related circRNA-miRNA-mRNA network in ESCC for novel biomarkers and therapeutic targets, differentially expressed circRNAs, miRNAs, and mRNAs were obtained from GEO datasets. A metastasis-associated circRNA-miRNA-mRNA ceRNA network in ESCC was constructed using Cytoscape software. The STRING database and Cytoscape were utilized for protein-protein interaction (PPI) interaction generation. The GEPIA2 database was used to obtain the expression of downstream targets and their prognostic value. The GO and KEGG enrichment analyzes were performed using the DAVID database. A dual-luciferase reporter assay was utilized to validate the target interaction among hsa_circ_0007551, miR-493-5p, and CXCL8/BMP2. Six metastasis-related DEcircRNAs overlapped from the GSE131969 and GSE150476 datasets. The ceRNA network was constructed containing six circRNAs, 15 miRNAs, and 86 mRNAs. In the ceRNA network, CXCL8 and BMP2, which were significantly associated with overall survival in ESCC patients, were chosen for further subnetwork construction. Then, a metastatic and survival-related ceRNA network containing hsa_circ_0007551, miR-493-5p, and two DEGs (CXCL8 and BMP2) was identified. hsa_circ_0007551 was upregulated in ESCC tissues and cells. In conclusion, this study identified novel circRNA-mediated ceRNA networks in ESCC metastasis, highlighting hsa_circ_0007551 and the CXCL8/BMP2 axis as potential biomarkers and therapeutic targets.

MED12 exon 2 mutation is the most frequent mutation associated with uterine leiomyomas. MED12 wild-type leiomyomas have a higher growth potential than mutant leiomyomas, suggesting that the mutation limits leiomyoma growth. MED12 forms a complex with CDK8 and is involved in the phosphorylation of RNA polymerase II, playing a role in transcriptional regulation. However, its mechanism of action in leiomyoma growth is not clear. We aimed to clarify the relationship between MED12 mutation status, response to gonadotropin-releasing hormone (GnRH) agonist treatment, and CDK8 activity in leiomyomas. We also examined the effects of CDK8 inhibitors on primary cultured uterine leiomyoma cells. We classified 44 surgically removed uterine leiomyomas into four groups according to GnRH agonist use and MED12 mutation status. CDK8 was co-immunoprecipitated from leiomyoma tissue extracts using MED12 antibody to test its kinase activity in vitro, and the amount of phosphorylated substrate was measured. Cell proliferation and apoptosis of primary cultured MED12 wild-type leiomyoma cells were evaluated in the presence of a CDK8 inhibitor and sex steroid hormones. Of the 44 leiomyomas tested, 11 MED12 wild-type leiomyomas without preoperative GnRH agonist treatment had significantly higher CDK8 activity than nine GnRH agonist-treated MED12 wild-type leiomyomas and 15 leiomyomas with MED12 mutations without GnRH agonist treatment. Treatment of primary cultured MED12 wild-type cells with CDK8 inhibitors significantly inhibited cell growth and increased apoptosis. MED12 wild-type leiomyoma cells without GnRH agonist treatment showed high CDK8 activity, and inhibition of CDK8 activity suppressed cell growth in vitro.

Dysregulated epigenetic control and DNA-repair defects are hallmarks of many cancers and neurodevelopmental disorders. ZMYM3, a chromatin-associated zinc-finger protein, orchestrates histone deacetylation, BRCA1-dependent homologous recombination (HR), and cytoskeletal organisation, yet the post-translational mechanisms that govern its activity remain largely unknown. Here we integrate global phosphoproteomics data to define the regulatory landscape of ZMYM3, with a focus on the highly recurrent phosphosite S464 located in its zinc-finger domain. S464 is detected in > 50% of curated human-cell-line datasets and is co-regulated with four upstream kinases (CDK13, HIPK1, CDK9, CLK3) and 15 binary interactors including BRCA1, HDAC6, and SWI/SNF components. Positively co-phosphorylated networks are enriched for chromatin remodelling, mitotic segregation, DNA-damage response, and cytoskeletal dynamics. cProSite analysis of patient tumours reveals striking S464 hyper-phosphorylation in breast and ovarian cancers, correlating with HR-deficiency signatures. ZMYM3 S464 emerges as a phospho-regulatory hub that coordinates epigenetic silencing, HR repair, and mitotic fidelity. Its cancer-type-specific upregulation offers a novel biomarker for HR-deficiency stratification and a therapeutic entry point for modulating BRCA1 function or epigenetic drug sensitivity; functional validation in HR-deficient models is now warranted.

Renal cell carcinoma (RCC) is a radiation-resistant tumor. Eg5, a spindle motor protein, plays a crucial role in centrosome separation and bipolar spindle formation during mitosis. We explored whether Eg5 is an important therapeutic target for treating RCC.

We selected radiation-resistant 786-O renal carcinoma cells and divided them into four groups: Control, 10 Gy irradiation, Eg5 inhibitor, and 10 Gy + Eg5 inhibitor. The proliferative ability of the tumor cells was assessed using the cell counting kit-8 assay; A transwell assay was employed to evaluate their invasive capacity. A clonogenic assay was performed to assess clonogenic survival. We divided the 786-O renal carcinoma cells into 10 Gy irradiation and 10 Gy + Eg5 inhibitor groups. Flow cytometry, cell cycle analysis, polymerase chain reaction (PCR), and western blotting were conducted to compare radiosensitivity between the two groups and to investigate potential underlying mechanisms.

The levels of cell proliferation, clonogenic survival, and migration in the 10 Gy + Eg5 inhibitor group (0.395 ± 0.007, 119.3 ± 7.513, 24.33 ± 2.333, respectively) were significantly lower than those in the control (0.772 ± 0.005, 294.3 ± 10.710, 83.00 ± 3.786, respectively) and 10 Gy groups (0.667 ± 0.006, 211.7 ± 9.528, 54.33 ± 2.728, respectively) (p < 0.05). Flow cytometry showed that the level of apoptosis in the 10 Gy + Eg5 inhibitor group (16.87 ± 2.476, 17.0%) was significantly higher than in the 10 Gy group (6.319 ± 0.380, 6.0%) (p < 0.05). Flow cytometry analysis further revealed that the proportion of cells in the G1 phase in the 10 Gy + Eg5 inhibitor group (10.037 ± 1.434) was lower than in the 10 Gy group (24.327 ± 2.252) (p < 0.05). PCR results showed that the messenger ribonucleic acid (mRNA) levels of H2AX, TP53BP1, XRCC1, and CDKN1A in the 10 Gy + Eg5 inhibitor group were significantly higher than those in the 10 Gy group (p < 0.05).

Eg5 inhibitors specifically bind to the Eg5 protein and disrupt mitosis, thereby improving the radiosensitivity of RCC by regulating the cell cycle. An Eg5 inhibitor combined with radiotherapy may represent an effective adjuvant therapy for RCC.

Exosomes derived from mesenchymal stem cells (MSC-exo) have the potential to regulate cancer progression by delivering various molecules, including long noncoding RNAs (lncRNAs). This study aimed to investigate the functional role and underlying mechanism of exosomal LINC00900, derived from human adipose-derived mesenchymal stem cells (MSCs), in thyroid cancer (TC). MSC-exo was isolated from conditioned medium using differential ultracentrifugation, observed under transmission electron microscopy, and identified through western blotting and an uptake assay. Cell viability, apoptosis, cell cycle progression, and invasion were evaluated by cell counting kit-8 (CCK-8) assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, flow cytometry, and transwell invasion assay, respectively. RNA-pull down and RNA immunoprecipitation assays were conducted to evaluate the interaction between LINC00900 and polypyrimidine tract binding protein 1 (PTBP1). A mouse model with subcutaneous xenografts of the TC cell line TPC-1 was used to assess tumor growth in vivo. The isolated MSC-exo exhibited classic exosome characteristics and could effectively be delivered to TPC-1 cells. MSC-exo significantly inhibited the proliferation of TPC-1 cells and promoted their apoptosis, as evidenced by a decreased optical density value and an increased percentage of apoptotic cells. Following incubation with MSC-exo, LINC00900 expression was markedly increased in TPC-1 cells. Overexpression of LINC00900 or inhibition of PTBP1 suppressed cell proliferation, elevated G0/G1 ratio, and promoted cell apoptosis. Additionally, LINC00900 expression was reduced, while PTBP1 protein levels were increased, in cancer tissues from TC patients. Furthermore, PTBP1 was identified as a target of LINC00900 and was negatively regulated by it. LINC00900 was also confirmed to inhibit cell autophagy by downregulating PTBP1. In vivo, MSC-exo inhibited tumor growth and autophagy while promoting apoptosis in TPC-1 cell xenografts. In conclusion, MSC-Exo carrying LINC00900 can effectively inhibit tumor cell growth in TC via suppression of PTBP1.

MZB1 is an endoplasmic reticulum (ER)-resident chaperone that facilitates immunoglobulin assembly and secretion, particularly polymeric IgM and dimeric IgA. Accumulating evidence links MZB1 to the regulation of intracellular Ca²⁺ signaling, integrin activation, and ER stress responses, which could influence innate-like B-cell functions and the maintenance of immune homeostasis. Aberrant expression of MZB1 has been implicated in the development of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), as well as in tumor progression, including hepatocellular carcinoma and multiple myeloma. In certain cancer, MZB1 expression is associated alterations in the tumor microenvironment that may be permissive for tumor progression. Conversely, its ability to enhance antibody responses suggests potential applications in immunotherapy. This review integrates current insights into MZB1 biology, summarizes its role in disease pathogenesis, and discusses future directions for therapeutic targeting.