Cancer In Clinical Setting Research Articles

MRNA vaccines: A powerful tool in cancer treatment

As an emerging immunotherapy, cancer vaccine is a method of introducing tumor antigens, genes encoding tumor antigens, immune cells and molecules into the body to activate specific immune responses to kill tumors. In April 2010, the world's first related drug, previz, was approved for marketing in United States. The drug extracts peripheral blood mononuclear cells from patients' autoimmune cells, activates them in vitro and then infuses them back into the treatment of asymptomatic or mildly symptomatic hormone-refractory advanced prostate cancer. mRNA vaccines have attracted much attention because of their high efficacy, specificity, versatility, ability to develop rapidly on a large-scale, low-cost production potential and safety. The mRNA vaccines and nano-agent delivery technology are considered to have great potential in cancer immunotherapy. In recent years, developments in the design and delivery methods of mRNA vaccines have accelerated the development and use of mRNA vaccinations against cancer in clinical settings. This review introduces optimization strategies of mRNA vaccinations against cancer, including coding and non-coding region optimization, and emphasizes mRNA vaccine delivery systems. Multiple nanoparticle vectors have currently been developed to improve mRNA stability and administration efficiency. At the same time, we discuss the applications of cancer therapy with mRNA vaccinations, its limitations and future challenges.

Platinum-perovskite nanocomposite-based Exosensor for specific detection of prostate cancer in clinical settings.

Exosomes, extracellular vesicles (EVs) with an average size of 50-150nm, transfer various biomolecules and exchange signaling molecules between cells in a paracrine manner. Molecular investigations have revealed that EVs can reflect real-time metabolic changes in normal- and cancer-origin cells and thus harbor valid diagnostic biomarkers. Despite these advantages, the detection of low concentrations of cancer cell EVs in biological fluids is still a great challenge. Here, a new electrochemical Exosensor based on platinum-perovskite is developed for the direct detection of EVs using a biotinylated monoclonal CD63 antibody as a capture element. The label-free method exhibited higher sensitivity with a lower limit of quantification of 2000 EVs/µL with a dynamic linear range (LDR) of 2000 to 14,000 EVs/μL compared with other available methods. To enhance the selectivity of detection, EVs were simultaneously sandwiched between secondary antibodies of PSA (prostate-specific antigen), as an FDA-approved prostate cancer biomarker. Data indicated that this Exosensor can distinguish normal and cancer EVs in samples from healthy individuals and prostate cancer patients. Taken together, this technology offers a unique approach to label-free quantification of EVs and cancer detection in the early stages.

Leveraging cfDNA fragmentomic features in a stacked ensemble model for early detection of esophageal squamous cell carcinoma.

4054 Background: In this study, we developed a stacked ensemble model that leverages cell-free DNA (cfDNA) fragmentation for the early detection of esophageal squamous cell carcinoma (ESCC). The model combined four fragmentomics features obtained from whole genome sequencing (WGS) and employed four machine learning algorithms. We evaluated the model’s generalizability in an independent validation cohort and an external cohort collected at different center. Additionally, the model’s robustness and repeatability were assessed across low coverage and repeated measured samples. The results underscore the promising potential of our model as an effective strategy for early diagnosis and management of ESCC in clinical settings. Methods: 256 healthy individuals and 243 patients diagnosed with esophageal cancer were enrolled in this study, including 47 healthy participants and 44 patients in the external cohort. Plasma samples from all participants were profiled by whole-genome sequencing (WGS). Fragmentomic features encompassed copy number variation (CNV), fragmentation size coverage (FSC), fragmentation size distribution (FSD), and nucleosome positioning (NP) were incorporated alongside machine learning models to develop an optimized classification model. The model generated a cancer score ranging from 0 to 1 for each cancer and noncancer sample, with a score closer to 1 indicating a higher probability of cancer. The performance of this model was assessed using an independent validation cohort and an external cohort, and model’s robustness and reproducibility were examined. Results: A stacked ensemble model was developed by integrating four cfDNA features and four machine learning algorithms. This integrated model exhibiting remarkable sensitivity of 91.8% (89/97) and specificity of 98.1% (102/104), and AUC of 0.986 in the independent validation cohorts using the cut-off of 0.69 selected at a specificity level of 98% (105) in the training cohort. The external cohort demonstrated a sensitivity of 86.4% (38/44) and a specificity of 95.7% (45/47) with the same cut-off. The model's performance remained consistent even at low sequencing coverage depths of 0.5× (AUC 0.978), providing valuable insights into the resilience and stability of our methodology and ascertained its practical applicability in scenarios with limited sequencing resources or constraints. Furthermore, our model demonstrated sensitivity in identifying early pathological features, with a sensitivity of 94.1% (16/17) for stage I and 91.4% (53/58) for tumors smaller than 3 cm. Conclusions: A stacked ensemble model was implemented in this study, utilizing cfDNA fragmentomics features with exceptional sensitivity for early detection of esophageal squamous cell carcinoma. The anticipated impact of this model is the enhancement of early detection strategies for esophageal cancer in clinical setting.

Myricetin inhibits 4 T1 breast tumor growth in mice via induction of Nrf-2/GPX4 pathway-mediated Ferroptosis

Ferroptosis is a recently identified form of programmed cell death that is iron-dependent and closely involved in the pathogenesis of breast cancer. Past studies have identified myricetin as being able to inhibit breast cancer growth through its targeting of apoptotic mechanisms, but the precise mechanisms whereby it exerts its antitumoral effects in breast cancer remain to be characterized in detail. Here, the effects of myricetin on the induction of ferroptosis in breast cancer cells were investigated. It was found that myricetin was able to significantly inhibit 4 T1 tumor cell viability and colony forming activity, increasing the level of MDA, Fe2+, and ROS within these cells. From a mechanistic perspective, myricetin was found to induce ferroptotic 4 T1 cell death via downregulating Nrf-2 and GPX4. In vivo experimentation demonstrated that myricetin treatment was sufficient to reduce the growth of subcutaneous breast tumors in female mice as evidenced by decreases in tumor weight and volume, while significantly inhibiting Nrf-2 and GPX4 expression within the tumors of treated mice. Myricetin is capable of readily suppressing breast tumor growth in mice via the induction of ferroptotic activity through the Nrf-2/GPX4 pathway. Myricetin may thus offer utility as a therapeutic agent for the management of breast cancer in clinical settings.

Comparative evaluation of Anyplex II HPV28 and Allplex HPV28 molecular assays for human papillomavirus detection and genotyping in anogenital cancer screening.

Persistent infection with high-risk human papillomavirus (HPV) is recognized as the main cause for the development of anogenital cancers. This study prospectively evaluated the diagnostic performance of the novel Allplex-HPV28 assay with the Anyplex-II-HPV28 to detect and genotype HPV in 234 consecutive swabs and 32 biopsies of the anogenital tract from 265 patients with atypical findings in cytomorphological screening. Agreement in HPV-DNA detection between the Anyplex-II and Allplex-HPV28 assays was 99%. There was a notable diversity in the HPV-virome, with the most prevalent high-risk HPV types being 16, 53, 66, and 68. The agreement rates for detecting these genotypes exceeded 93% between the Anyplex-II and Allplex-HPV28 assays. Discrepancies in test results were solely noted for Anyplex-II-HPV28 results with a low signal intensity of "+", and for Allplex-HPV28 results with cycle thresholds of ≥36. The semi-quantitative analysis of HPV-DNA loads showed significant agreement between the Anyplex-II-HPV28 and Allplex-HPV28 assays (p < 0.001). Furthermore, HPV-DNA detection rates and mean HPV-DNA loads significantly correlated with the grade of abnormal changes identified in cytopathological assessment, being highest in cases of HSIL, condyloma accuminatum, and squamous cell carcinoma. Overall agreement rates for detecting specific HPV-types among the Anyplex-II and Allplex-HPV28 assays exceeded 99.5% in cases of atypical squamous cells, condyloma accuminatum, and squamous cell carcinoma. The novel Allplex-HPV28 assay shows good diagnostic performance in detecting and genotyping HPV commonly associated with anogenital cancers. Consequently, this assay could offer substantial potential for incorporation into future molecular screening programs for anogenital cancers in clinical settings.

A CARM1 Inhibitor Potently Suppresses Breast Cancer Both In Vitro and In Vivo.

CARM1, belonging to the protein arginine methyltransferase (PRMT) family, is intricately associated with the progression of cancer and is viewed as a promising target for both cancer diagnosis and therapy. However, the number of specific and potent CARM1 inhibitors is limited. We herein discovered a CARM1 inhibitor, iCARM1, that showed better specificity and activity toward CARM1 compared to the known CARM1 inhibitors, EZM2302 and TP-064. Similar to CARM1 knockdown, iCARM1 suppressed the expression of oncogenic estrogen/ERα-target genes, whereas activated type I interferon (IFN) and IFN-induced genes (ISGs) in breast cancer cells. Consequently, iCARM1 potently suppressed breast cancer cell growth both in vitro and in vivo. The combination of iCARM1 with either endocrine therapy drugs or etoposide demonstrated synergistic effects in inhibiting the growth of breast tumors. In summary, targeting CARM1 by iCARM1 effectively suppresses breast tumor growth, offering a promising therapeutic approach for managing breast cancers in clinical settings.

Abstract PO1-07-03: An Accurate Breast Cancer Diagnosis Method Using a Multi-Feature Fusion Neural Network on Contrast-Enhanced Spectral Mammography

Abstract Objectives: Our study aims to develop an accurate and comprehensive deep neural network capable of classifying CESM images to aid in the early detection and diagnosis of breast cancer in clinical settings. Methods: We enrolled diagnostic CESM examinations conducted between January 1, 2019 and January 17, 2021. We developed and tested the performance of a multi-feature fusion network for breast lesion classification by combining low-energy (LE) and dual-energy subtracted (DES) images, dual-view, and bilateral information using a large and diverse CESM dataset. We have evaluated the ability of the proposed network to generalize on external datasets and the results were reported using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Results: In the study period 1973CESMs were included. Mean age was 53 years ± 12 (standard deviation). In the internal test dataset, the model with CESM (LE +DES) inputs combined not only bilateral information (left and right breasts) but also dualview information (CC and MLO), achieved best diagnosis performance with AUC of 0.96 [95% confidence interval (CI): 0.95–0.97], accuracy of 0.9 [95% confidence interval (CI): 0.88–0.92], sensitivity of 0.84 [95% confidence interval (CI): 0.80–0.88] and specificity of 0.93 [95% confidence interval (CI): 0.91–0.95], while the model with LE inputs only got an AUC of 0.94 [95% (CI): 0.93–0.95], accuracy of 0.88 [95% confidence interval (CI): 0.86–0.90], sensitivity of 0.79 [95% confidence interval (CI): 0.74–0.83] and specificity of 0.93 [95% confidence interval (CI): 0.91–0.95] (external dataset: an AUC of 0.90 [95% (CI): 0.85–0.94], accuracy of 0.84 [95% confidence interval (CI): 0.78–0.89], sensitivity of 0.77 [95% confidence interval (CI): 0.61–0.88] and specificity of 0.87 [95% confidence interval (CI):0.80–0.92]). Conclusion: CESM is a promising technique in breast cancer diagnosis due to its high feasibility and potential. The results demonstrate that left-right breast fusion and dual-view fusion are helpful for accurate diagnosis on CESM images. Specifically, dual-energy subtracted (DES) images generated by CESM improve diagnostic accuracy when compared to low-energy (LE) images alone. Keywords: Contrast-enhanced spectral mammography; Deep neural network; Breast cancer diagnosis; Multi-feature fusion Citation Format: Yipeng Song, Wei Jiang. An Accurate Breast Cancer Diagnosis Method Using a Multi-Feature Fusion Neural Network on Contrast-Enhanced Spectral Mammography [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-07-03.

Abstract 5260: Combination activity of eribulin liposomal formulation and anti-PD-1 antibody after tumor regrowth during anti-PD-1 antibody treatment in mice

Abstract Eribulin (ERI) has been reported a microtubule dynamics inhibitor with unique tumor microenvironment modulations such as vascular remodeling activity. In the previous meeting (AACR2022, 2023), we reported that ERI and liposomal formulation of ERI (ERI-LF) also have immunomodulatory activity that induces CD8+ T cells via its vascular remodeling activity and ERI-LF showed more potent immune modulation and combination activities with anti-PD-1 antibody (PD-1 Ab) than ERI in syngeneic mice models and humanized mice models. Although immune-checkpoint inhibitors (ICI) are using as a key drug for various types of cancers in clinical setting, several clinical questions regarding suitable therapies after ICI therapy and efficacy of ICI rechallenge are remaining. In this study, we evaluated anti-tumor activities of combination of ERI-LF and PD-1 Ab in two syngeneic transplantation models using mouse non-small lung cancer cells, P-glycoprotein-knockout (Pgp-KO) KLN205 cells and Pgp-KO LL2 cells. As a result, combination of 1mg/kg ERI-LF (Q7D×2) with PD-1 Ab (200 ug/head, twice a week ×2 weeks) showed significant stronger antitumor activity compared with each monotherapy in only Pgp-KO KLN205 model, in which ERI-LF increased intratumoral microvascular density as a vascular remodeling activity, not in Pgp-KO LL2 model. We next conducted continuous treatment of PD-1 Ab in Pgp-KO KLN205 model to investigate tumor regrowth during treatment of PD-1 Ab. In this model, tumor growth was inhibited by PD-1 Ab until about two weeks after initiation of the treatment and then this inhibitory activity disappeared after two weeks even by continuous treatment of PD-1 Ab. We performed flow cytometry analysis (FCM) for tumor-infiltrating immune cells and RNAseq analysis using regrowing tumors compared with non-treatment tumors. Expressions of mRNA of several immune inhibitory receptors were upregulated in tumors with regrowth, although CD4+ cells and CD8+ cells were also increased in FCM using tumor samples. Furthermore, we investigated anti-tumor activity of combination of ERI-LF and PD-1 Ab against tumors which changed from inhibitory phase to regrowth phase during PD-1 Ab treatment in Pgp-KO KLN205 model. The combination of ERI-LF at 1mg/kg (Q7D×3) and PD-1 Ab (200 ug/head, twice a week ×3 weeks) also showed potent anti-tumor activity against tumors with regrowth by prior PD-1 Ab treatment as well as PD-1 Ab-naïve tumor, suggesting that this combination therapy might be effective after prior ICI therapy. Currently, Phase 1b/2 clinical trial of ERI-LF plus nivolumab in patients with selected solid cancers (NCT04078295) is underway. Patients with or without prior ICI therapy were enrolled in a small cell lung cancer cohort of this clinical study. Our preclinical results might provide a scientific rationale for a uniqueness of ERI-LF as a post ICI therapy. Citation Format: Moe Tamura, Yuki Niwa, Taro Semba. Combination activity of eribulin liposomal formulation and anti-PD-1 antibody after tumor regrowth during anti-PD-1 antibody treatment in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5260.

Adaptive Design of Nanovesicles Overcoming Immunotherapeutic Limitations of Chemotherapeutic Drugs through Poliovirus Receptor Blockade.

Chemotherapy is currently a widely used treatment for cancer in clinical settings. Some chemotherapeutic drugs such as oxaliplatin (OXA) can cause tumor immunogenic cell death (ICD), activate immunity, and realize chemoimmunotherapy for tumors. However, the low degree of accumulation and immunosuppressive microenvironment in tumors limit the immunotherapeutic efficacy of these drugs. T cell immunoreceptor with Ig and ITIM domains (TIGIT)/poliovirus receptor (PVR) is an inhibitory immune checkpoint pathway involved in mediating natural killer (NK) cell and T cell exhaustion in tumors. TIGIT expression is up-regulated in NK cells and CD8+ T cells during tumor development. Moreover, we first found that tumors upregulated PVR expression after OXA treatment in previous work. Here, we systematically analyzed the effects of OXA on the TIGIT/PVR pathway, further proving the effectiveness of the combination of OXA and TIGIT/PVR blocking combination. We developed engineered TIGIT-expressing cell membrane nanovesicles loaded with OXA (OXA@TIGIT MVs) for synergistic cancer therapy. OXA@TIGIT showed good efficacy in several cancer models, leading to tumor regression, effectively inhibiting tumor growth and prolonging mouse survival. Furthermore, the OXA@TIGIT MVs activate a strong tumor-specific immune response in the body, providing long-term (more than 2 months) protection from tumor reactivation in the B16F10 melanoma rechallenge mouse model.

An Outlook of the Structure Activity Relationship (SAR) of Naphthalimide Derivatives as Anticancer Agents.

The efficacy of drugs against cancer in clinical settings may be limited due to pharmacokinetic issues, side effects and the emergence of drug resistance. However, a class of anticancer drugs known as naphthalimides have proven to be very effective. These derivatives have demonstrated to be effective in treating different types of cancers and exhibit strong DNA binding affinity. The anticancer properties of the naphthalimide derivatives allow them to target a number of cancer cell lines. Researchers have investigated the anticancer activity of numerous naphthalimide derivatives, such as heterocyclic fused, non-fused substituted, metal-substituted and carboxamide derivatives. Surprisingly, some derivatives demonstrate greater activity than the reference norms, such as cisplatin, amonafide, mitonafide and others and are selective against many cell lines. The primary objective of this research is to comprehend the effects of various substitution patterns on the structure-activity relationship (SAR) of these derivatives and the instances in which they enhance or reduce this biological activity.

Aging-Associated ALKBH5-m6A Modification Exacerbates Doxorubicin-Induced Cardiomyocyte Apoptosis Via AT-Rich Interaction Domain 2.

Chemotherapy-induced cardiovascular disease is a growing concern in the elderly population who have survived cancer, yet the underlying mechanism remains poorly understood. We investigated the role of ALKBH5 (AlkB homolog 5), a primary N6-methyladenosine (m6A) demethylase, and its involvement in m6A methylation-mediated regulation of targets in aging-associated doxorubicin-induced cardiotoxicity. To validate the relationship between doxorubicin-induced cardiotoxicity and aging, we established young and old male mouse models. ALKBH5 expression was modulated through adeno-associated virus 9 (in vivo), Lentivirus, and siRNAs (in vitro) to examine its impact on cardiomyocyte m6A modification, doxorubicin-induced cardiac dysfunction, and remodeling. We performed mRNA sequencing, methylated RNA immunoprecipitation sequencing, and molecular assays to unravel the mechanism of ALKBH5-m6A modification in doxorubicin-induced cardiotoxicity. Our data revealed an age-dependent increase in doxorubicin-induced cardiac dysfunction, remodeling, and injury. ALKBH5 expression was elevated in aging mouse hearts, leading to reduced global m6A modification levels. Through mRNA sequencing and methylated RNA immunoprecipitation sequencing analyses, we identified ARID2 (AT-rich interaction domain 2) as the downstream effector of ALKBH5-m6A modulation in cardiomyocytes. Further investigations revealed that ARID2 modulates DNA damage response and enhances doxorubicin-induced cardiomyocyte apoptosis. Our findings provide insights into the role of ALKBH5-m6A modification in modulating doxorubicin-induced cardiac dysfunction, remodeling, and cardiomyocyte apoptosis in male mice. These results highlight the potential of ALKBH5-targeted treatments for elderly patients with cancer in clinical settings.

Inflammatory cell death induced by 5-aminolevulinic acid-photodynamic therapy initiates anticancer immunity.

Inflammatory cell death is a form of programmed cell death (PCD) that induces inflammatory mediators during the process. The production of inflammatory mediators during cell death is beneficial in standard cancer therapies as it can break the immune silence in cancers and induce anticancer immunity. Photodynamic therapy (PDT) is a cancer therapy with photosensitizer molecules and light sources to destroy cancer cells, which is currently used for treating different types of cancers in clinical settings. In this study, we investigated if PDT using 5-aminolevulinic (5-ALA-PDT) causes inflammatory cell death and, subsequently, increases the immunogenicity of cancer cells. Mouse breast cancer (4T1) and human colon cancer (DLD-1) cells were treated with 5-ALA for 4 hours and then irradiated with a light source. PCD induction was measured by western blot analysis and FACS. Morphological changes were determined by transmission electron microscopy (TEM). BALB/c mice were injected with cell-free media, supernatant of freeze/thaw cells or supernatant of PDT cells intramuscular every week for 4 weeks and then challenged with 4T1 cells at the right hind flank of BALB/c. Tumor growth was monitored for 12 days. We found that 5-ALA-PDT induces inflammatory cell death, but not apoptosis, in 4T1 cells and DLD-1 cells in vitro. Moreover, when mice were pretreated with 5-ALA-PDT culture supernatant, the growth of 4T1 tumors was significantly suppressed compared to those pretreated with freeze and thaw (F/T) 4T1 culture supernatant. These results indicate that 5-ALA-PDT induces inflammatory cell death which promotes anticancer immunity in vivo.

Carbon Dots as Advanced Drug-Delivery Nanoplatforms for Antiinflammatory, Antibacterial, and Anticancer Applications: A Review

Carbon dots (CDs), as rapidly developing nanomaterials, give new prospects for the treatment of various diseases. Their great biocompatibility and wide specific surface area make CDs excellent drug-delivery vehicles because they improve cellular uptake and absorption and allow for medications to bind more easily. CDs offer enormous potential as delivery systems for antiinflammatory medications. The activities of antiinflammatory drugs delivered by CDs are higher than those of free drugs. They also have controlled release, thus enhancing the cumulative effect at the inflammation site and improving pharmacokinetics. Compared with free small-molecule antibacterial medicines, CD-based drug-delivery systems have higher antibacterial efficacies, better targeting, increased cellular uptake and internalization efficiency, and decreased systemic side effects. The benefits of using CDs as anticancer drug carriers include high drug loading, increased targeting, lower drug dosage, regulated drug release, and synergistic photothermal therapy, which offers a novel approach to the diagnosis and treatment of cancer in clinical settings. However, it is important to consider the biosafety, toxicity, and impact of CDs on the immune system of an organism before using them as drug-delivery vehicles for clinical diagnosis and therapy. This review discusses the use of CDs in the delivery of antiinflammatory, antibacterial, and anticancer drugs and summarizes the current advantages and challenges of using CDs for drug delivery.

Abstract 3230: Tumor microenvironment modulation by immunotherapy sensitizes solid tumors to radiation

Abstract Radiation therapy (RT) has been prevalently implemented to treat cancer in clinical settings by inducing DNA damage in tumor cells. However, tumor microenvironmental factors such as severe hypoxic conditions and vascular anomalies attenuate the therapeutic efficacy of RT, thus resulting in unsatisfactory outcomes in solid tumors. Recently, Immune checkpoint blockade (ICB) has improved immune recognition to tumor cells and normalized tumor vasculature to diminish hypoxia in solid tumors. Herein, we suggest that RT combined with ICB synergistically alters tumor microenvironments, thus facilitating the recruitment of cytotoxic immune cells into tumors as well as sensitizing radiation effectiveness. RT in combination with ICB not only normalized tumor vasculature to reduce hypoxia, but also increased anti-tumor effects from immune-mediated toxicity and DNA damage-mediated apoptosis in several solid tumor-bearing mouse models to a greater extent than did either monotreatment of RT or ICB. This study will provide mechanistic insight into synergistic effects conferred by RT and ICB as well as a strong preclinical rationale for combining the two therapeutic modalities in human cancers. Citation Format: Minjeong Kang, DaeYong Lee, Yifan Wang, Betty Kim, Wen Jiang. Tumor microenvironment modulation by immunotherapy sensitizes solid tumors to radiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3230.

Diagnostic value of tumor-associated autoantibodies panel in combination with traditional tumor markers for lung cancer.

The diagnostic value of 7 tumor-associated autoantibodies (AABs) including p53, PGP9.5, SOX2, GAGE7, GBU4-5, MEGEA1, and CAGE for the detection of lung cancer has shown inconsistency in several studies. This study aimed to confirm the diagnostic value of 7AABs and to explore whether the diagnostic value would be improved by combining them with 7 traditional tumor-associated antigens (CEA, NSE, CA125, SCC, CA15-3, pro-GRP, and CYFRA21-1) in clinical settings. The plasma levels of 7-AABs were detected by enzyme-linked immunosorbent assay (ELISA) in 533 lung cancer cases and 454 controls. The 7 tumor antigens (7-TAs) were measured by Electrochemiluminescence immunoassay with Cobas 6000 (Roche, Basel, Switzerland). The positive rate of 7-AABs in the lung cancer group (64.00%) was significantly higher than that of healthy controls (47.90%). The 7-AABs panel was able to discriminate lung cancer from controls with a specificity of 51.50%. After combining the 7-AABs with 7-TAs, the sensitivity showed a significantly enhancement compared with 7AABs panel alone (92.09% vs 63.21%). In patients with resectable lung cancer, the combination of 7-AABs and 7-TAs improved the sensitivity from 63.52% to 97.42. In conclusion, our study found that the diagnostic value of 7-AABs was enhanced when combined with 7-TAs. This combined panel could be used as promising biomarker to detect resectable lung cancer in clinical settings.

Novel exosome-related risk signature as prognostic biomarkers in glioblastoma.

Exosomes are progressively being detected as an indicator for the diagnosis and prognosis of cancer in clinical settings. Many clinical trials have confirmed the impact of exosomes on tumor growth, particularly in anti-tumor immunity and immunosuppression of exosomes. Therefore, we developed a risk score based on genes found in glioblastoma-derived exosomes. In this study, we used the TCGA dataset as the training queue and GSE13041, GSE43378, GSE4412, and CGGA datasets as the external validation queue. Based on machine algorithms and bioinformatics methods, an exosome-generalized risk score was established. We found that the risk score could independently predict the prognosis of patients with glioma, and there were significant differences in the outcomes of patients in the high- and low-risk groups. Univariate and multivariate analyses showed that risk score is a valid predictive biomarker for gliomas. Two immunotherapy datasets, IMvigor210 and GSE78220, were obtained from previous studies. A high-risk score showed a significant association with multiple immunomodulators that could act on cancer immune evasion. The exosome-related risk score could predict the effectiveness of anti-PD-1 immunotherapy. Moreover, we compared the sensitivity of patients with high- and low-risk scores to various anti-cancer drugs and found that patients with high-risk scores had better responses to a variety of anti-cancer drugs. The risk-scoring model established in this study provides a useful tool to predict the total survival time of patients with glioma and guide immunotherapy.

Functionalized Nanoparticle Drug Delivery System Applied to the Diagnosis and Treatment of Tumor Cells

Chemotherapy is currently an important modality in the treatment of cancer and is widely used in the treatment of many cancers. However, the main problem with chemotherapy is the highly toxic side effects. How improve the efficacy of drugs and reduce their side effects has been a challenge for cancer treatment research. With the booming development of nanotechnology, functionalized nanomaterials are widely used for drug delivery and the treatment of tumors. Nanomaterials have unique physical, chemical, and optical properties, and the drug delivery system constructed by using multifunctional nanomaterials can not only precisely kill tumor cells to reduce damage to normal tissues, but also combine multiple therapeutic modalities simultaneously to improve the treatment effect of cancer. Therefore, the development of precise nano-targeted therapeutic techniques is of great importance for the treatment of cancer in clinical settings. In this thesis, we constructed various nano-drug delivery systems based on functionalized nanomaterials and applied them to drug delivery to tumors and multimodal therapy. These studies will help advance the development of nanomolecular drug delivery technologies to improve the therapeutic efficacy of drugs, reduce side effects and toxicity, and provide safer and more effective drug treatment options for clinical therapy.

Enhancing an Oxidative "Trojan Horse" Action of Vitamin C with Arsenic Trioxide for Effective Suppression of KRAS-Mutant Cancers: A Promising Path at the Bedside.

The turn-on mutations of the KRAS gene, coding a small GTPase coupling growth factor signaling, are contributing to nearly 25% of all human cancers, leading to highly malignant tumors with poor outcomes. Targeting of oncogenic KRAS remains a most challenging task in oncology. Recently, the specific G12C mutant KRAS inhibitors have been developed but with a limited clinical outcome because they acquire drug resistance. Alternatively, exploiting a metabolic breach of KRAS-mutant cancer cells related to a glucose-dependent sensitivity to oxidative stress is becoming a promising indirect cancer targeting approach. Here, we discuss the use of a vitamin C (VC) acting in high dose as an oxidative "Trojan horse" agent for KRAS-mutant cancer cells that can be potentiated with another oxidizing drug arsenic trioxide (ATO) to obtain a potent and selective cytotoxic impact. Moreover, we outline the advantages of VC's non-natural enantiomer, D-VC, because of its distinctive pharmacokinetics and lower toxicity. Thus, the D-VC and ATO combination shows a promising path to treat KRAS-mutant cancers in clinical settings.

Global Research Mapping of Psycho-Oncology Between 1980 and 2021: A Bibliometric Analysis.

Background and AimPsycho-oncology is a cross-disciplinary and collaborative sub-specialty of oncology that focuses on the psychological, behavioral, ethical, and social aspects of cancer in clinical settings. The aim of this bibliometric study was to analyze and characterize the research productivity and trends in psycho-oncology between 1980 and 2021.MethodologyIn May 2022, the Scopus® database was searched for psycho-oncology-related publications using predetermined search keywords with specific restrictions. Lotka’s law was applied to check the authors’ productivity, while Bradford’s law was used to assess the core journals in this field. The data was analyzed for different bibliometric indicators in the Biblioshiny package, an RStudio tool for bibliometric analysis.ResultsThe initial search resulted in a total of 2,906 publications. Of which, 1,832 publications were included in the final analysis, published between 1980 and 2021. The analyzed publications were written by 7,363 authors from 74 countries and published in 490 journals. There has been a significant increase in psycho-oncology-related publications after 2010. The most productive year was 2021 (n = 365). The annual scientific growth rate was found to be 13.9%. The most relevant leading author in terms of publications was Luigi Grassi from the University of Ferrara, Italy (n = 42). Lotka’s law found that the number of authors declined as the number of papers written increased. The core journals were Psycho-Oncology, Supportive Care in Cancer, and Journal of Psychosocial Oncology. The most frequently used author’s keywords other than searching keywords were cancer, oncology, quality of life, depression, and anxiety. Recent psycho-oncology-related topics included mental health, COVID-19 infection in humans, people, pandemic, and tumor. The University of Sydney was the top-ranked institution. The leading country in terms of publications, citations, corresponding author country, and international collaboration was the United States of America (United States). The United States had the strongest collaboration with Australia and Canada.ConclusionThe research hotspots include mental health conditions and interventions in cancer patients. We identified international collaboration and research expenditure to be strongly associated with psycho-oncology research productivity. Researchers’ collaboration, which is visible among developed countries, should be extended to low-income countries in order to expand psycho-oncology-related research and understanding.

Circulating Virus-Host Chimera DNAs in the Clinical Monitoring of Virus-Related Cancers.

Simple SummaryCell-free tumor DNA (ctDNA), the DNA released into circulation from tumors, is a promising tumor marker with versatile applications. The associations of the amount, somatic mutation frequency, and epigenetic modifications of ctDNA with the tumor burden, tumor behavior, and prognosis have been widely investigated in different types of tumors. However, there are still some challenging issues to be resolved before ctDNA can complement or even replace current serum tumor markers. We propose employing exogenous viral DNA integration that produces unique virus–host chimera DNA (vh-DNA) at junction sites. Cell-free vh-DNA may become a new biomarker because it overcomes background interference detection problems, takes advantage of virus tropism to localize the tumor, and acts as a universal marker for monitoring clonal expansion or tumor loads in tumors related to oncogenic viruses.The idea of using tumor-specific cell-free DNA (ctDNA) as a tumor biomarker has been widely tested and validated in various types of human cancers and different clinical settings. ctDNA can reflect the presence or size of tumors in a real-time manner and can enable longitudinal monitoring with minimal invasiveness, allowing it to be applied in treatment response assessment and recurrence monitoring for cancer therapies. However, tumor detection by ctDNA remains a great challenge due to the difficulty in enriching ctDNA from a large amount of homologous non-tumor cell-free DNA (cfDNA). Only ctDNA with nonhuman sequences (or rearrangements) can be selected from the background of cfDNA from nontumor DNAs. This is possible for several virus-related cancers, such as hepatitis B virus (HBV)-related HCC or human papillomavirus (HPV)-related cervical or head and neck cancers, which frequently harbor randomly integrated viral DNA. The junction fragments of the integrations, namely virus–host chimera DNA (vh-DNA), can represent the signatures of individual tumors and are released into the blood. Such ctDNA can be enriched by capture with virus-specific probes and therefore exploited as a circulating biomarker to track virus-related cancers in clinical settings. Here, we review virus integrations in virus-related cancers to evaluate the feasibility of vh-DNA as a cell-free tumor marker and update studies on the development of detection and applications. vh-DNA may be a solution to the development of specific markers to manage virus-related cancers in the future.