Target In Cancer Research Articles

New Insights in ATP Synthesis as Therapeutic Target in Cancer and Angiogenic Ocular Diseases.

Lactate and ATP formation by aerobic glycolysis, the Warburg effect, is considered a hallmark of cancer. During angiogenesis in non-cancerous tissue, proliferating stalk endothelial cells (ECs) also produce lactate and ATP by aerobic glycolysis. In fact, all proliferating cells, both non-cancer and cancer cells, need lactate for the biosynthesis of building blocks for cell growth and tissue expansion. Moreover, both non-proliferating cancer stem cells in tumors and leader tip ECs during angiogenesis rely on glycolysis for pyruvate production, which is used for ATP synthesis in mitochondria through oxidative phosphorylation (OXPHOS). Therefore, aerobic glycolysis is not a specific hallmark of cancer but rather a hallmark of proliferating cells and limits its utility in cancer therapy. However, local treatment of angiogenic eye conditions with inhibitors of glycolysis may be a safe therapeutic option that warrants experimental investigation. Most types of cells in the eye such as photoreceptors and pericytes use OXPHOS for ATP production, whereas proliferating angiogenic stalk ECs rely on glycolysis for lactate and ATP production. (J Histochem Cytochem XX.XXX-XXX, XXXX).

Phospholipid-Anchored Ligand Conjugation on Extracellular Vesicles for Enhanced Cancer Targeting.

Extracellular vesicles (EVs) are recognized as potential candidates for next-generation drug delivery systems. However, the inherent cancer-targeting efficiency is unsatisfactory, necessitating surface modification to attach cell-binding ligands. By utilizing phospholipase D from Streptomyces in combination with maleimide-containing primary alcohol, the authors successfully anchored ligands onto milk-derived EVs (mEVs), overcoming the issues of ligand leakage or functional alteration seen in traditional methods. Quantitative nano-flow cytometry demonstrated that over 90% of mEVs are effectively modified with hundreds to thousands of ligands. The resulting mEV formulations exhibited remarkable long-term stability in conjugation proportion, ligand number, size distribution, and particle concentration, even after months of storage. It is further shown that conjugating transferrin onto mEVs significantly enhanced cellular uptake and induced pronounced cytotoxic effects when loaded with paclitaxel. Overall, this study presents a highly efficient, stable, cost-effective, and scalable ligand conjugation approach, offering a promising strategy for targeted drug delivery of EVs.

MicroRNA-875-5p inhibits the growth and metastasis of cervical cancer cells by promoting autophagy and apoptosis and inhibiting the epithelial-mesenchymal transition

IntroductionMicroRNA-875-5p (miR-875-5p) is a cancer-related microRNA. It has been demonstrated that miR−875−5p participates in the development of various types of cancer such as hepatocellular carcinoma, gastric carcinoma, prostate and bladder cancer. Previous research suggested that miR-875 is implicated in the development of cervical cancer cells. However, the exact role and function of miR−875−5p in cervical cancer remain unexplored. It is important to examine the role and function of miR-875-5p and the associated signaling pathway, as the findings may have diagnostic and therapeutic significance. Thus, in this study, we investigated the effect of miR-875-5p on the growth and metastasis of cervical cancer cells and the possible underlying mechanisms.MethodsReverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-875-5p in cervical cancer cells and normal cervical epithelium. After overexpression or co-expression of miR-875-5p in cells, the changes in cell function were analyzed. Western blot was used to detect the expression changes of epithelial-mesenchymal transition (EMT) -related proteins and autophagy-related proteins.ResultsFunctional studies demonstrated that miR-875-5p overexpression significantly inhibited the proliferation, migration, invasion, and EMT, and promotes apoptosis and autophagy of cervical cancer cells., while miR-875-5p knockdown promoted the proliferation, migration, invasion, and EMT, and inhibited apoptosis and autophagy cervical cancer cells. Furthermore, Western blot results showed that overexpression of miR-875-5p downregulated the expressions of N-cadherin, Snail, Vimentin and microtubule-associated protein 1 light chain 3B I (LC3B I). Conversely, miR-875-5p upregulated the expression of E-cadherin.ConclusionIn conclusion, our findings suggest that miR-875-5p functions as a tumor inhibitor suppressing the growth and metastasis of cervical cancer. Overexpression of miR-875-5p inhibits malignant behavior and promotes autophagy and apoptosis in cervical cancer cells. These findings advance our understanding of the role and function of miR-875-5p in cervical cancer and could facilitate the development of early genetic markers or biomarkers and therapeutic targets for cervical cancer.

The m6A reader HNRNPC predicts adverse prognosis and promotes the progression of colorectal cancer.

As a critical m6A RNA methylation regulator, HNRNPC has been revealed to serve as potential biomarkers in various human cancers. The specific expression and significance of HNRNPC in colorectal cancer remain unknown. This study aimed to confirm HNRNPC expression level and evaluate its function in colorectal cancer progression. 101 paired tissue samples were collected from colorectal cancer patients. HNRNPC levels in colorectal cancer were detected using PCR. CCK8 and transwell assays were conducted to estimate the effect of HNRNPC on cell growth and metastasis with the regulation of HNRNPC by cell transfection. Upregulated HNRNPC was observed in colorectal cancer compared with normal tissues and cells. The higher HNRNPC levels in tumor tissues were associated with the advanced TNM stage and positive lymph node metastasis. Meanwhile, HNRNPC upregulation could indicate adverse outcomes of colorectal cancer patients. In vitro, the knockdown of HNRNPC significantly suppressed the proliferation, migration, and invasion of colorectal cancer cells. Upregulated HNRNPC served as a biomarker for the prognosis and development of colorectal cancer, which provides a novel therapeutic target for colorectal cancer.

Potential clinical applications of extracellular vesicles in pancreatic cancer: exploring untapped opportunities from biomarkers to novel therapeutic approaches

Pancreatic cancer is a highly lethal and metastatic malignancy, mainly because it often remains undetected until advanced stages due to the limitations of current diagnostic methods, rendering currently available therapies ineffective. Therefore, it is imperative to identify useful biomarkers for early diagnosis and new therapeutic targets for pancreatic cancer. Recently, extracellular vesicles have emerged as promising biomarkers for the diagnosis and prognosis of pancreatic cancer. Given their presence in various bodily fluids, extracellular vesicles offer a non-invasive approach through liquid biopsy to detect and monitor cancer progression. In this review, we comprehensively examine the multifaceted roles of extracellular vesicles in the progression of cancer, while also exploring their potential as diagnostic, prognostic, and therapeutic biomarkers in the context of pancreatic cancer.

Claudin-18 status and its correlation with HER2 and PD-L1 expression in gastric cancer with peritoneal dissemination

Abstract Background Gastric cancer with peritoneal dissemination (PD) has a dismal prognosis, and current treatments have shown little efficacy. CLDN18.2-targeted therapies have shown promising efficacy against gastric cancers that express high levels of CLDN18. Because of the limited information regarding CLDN18.2 status in PD, we analyzed PD-positive gastric cancers for CLDN18 status in both primary and PD, along with HER2 and PD-L1 combined positive score (CPS). Methods Immunohistochemical analyses were performed on 84 gastric cancer cases using paired primary and PD tissue samples. Results At 40% cut-off, CLDN18 was positive in 57% (48/84) primary tumors and in 44% (37/84) PDs. At 75% cut-off, 28.6% (24/84) primary tumors and 20.2% (17/84) PDs were CLDN18-positive. The concordance rate between primary tumors and PD was 79.8% at 40% cut-off and 75% at 75% cut-off. When comparing biopsy and surgical specimens, the concordance rates were 87.5% at 40% cut-off and 81.3% at 75% cut-off. Within a tumor, the superficial area tended to have a higher CLDN18-positive rate than the invasive front (P = 0.001). Although HER2 -positivity was only 11.9% in this cohort, CLDN18 positivity in HER2-negative tumors (n = 74) was relatively high: 60.8% at 40% cut-off and 28.4% at 75% cut-off. Among double-negative (HER2 − and PD-L1 CPS < 1) tumors, CLDN18 positivity was 67.6% at 40% cut-off and 26.5% at 75% cut-off. Conclusions CLDN18 expression is generally maintained in PD and is relatively high even in double-negative tumors, making it a promising therapeutic target for PD-positive gastric cancer.

Molecular Targeting in Non-Small Cell Lung Cancer: Advances in EGFR, ROS1, ALK, and MET Pathways

Molecular Targeting in Non-Small Cell Lung Cancer: Advances in EGFR, ROS1, ALK, and MET Pathways

The heparin-binding domain of VEGF165 directly binds to integrin αvβ3 and VEGFR2/KDR D1: a potential mechanism of negative regulation of VEGF165 signaling by αvβ3

VEGF-A is a key cytokine in tumor angiogenesis and a major therapeutic target for cancer. VEGF165 is the predominant isoform of VEGF-A, and it is the most potent angiogenesis stimulant. VEGFR2/KDR domains 2 and 3 (D2D3) bind to the N-terminal domain (NTD, residues 1–110) of VEGF165. Since removal of the heparin-binding domain (HBD, residues 111–165) markedly reduced the mitogenic activity of the growth factor, it has been proposed that the HBD plays a critical role in the mitogenicity of VEGF165. Here, we report that αvβ3 specifically bound to the isolated VEGF165 HBD but not to VEGF165 NTD. Based on docking simulation and mutagenesis, we identified several critical amino acid residues within the VEGF165 HBD required for αvβ3 binding, i.e., Arg123, Arg124, Lys125, Lys140, Arg145, and Arg149. We discovered that VEGF165 HBD binds to the KDR domain 1 (D1) and identified that Arg123 and Arg124 are critical for KDR D1 binding by mutagenesis, indicating that the KDR D1-binding and αvβ3-binding sites overlap in the HBD. Full-length VEGF165 mutant (R123A/R124A/K125A/K140A/R145A/R149A) defective in αvβ3 and KDR D1 binding failed to induce ERK1/2 phosphorylation, integrin β3 phosphorylation, and KDR phosphorylation and did not support proliferation of endothelial cells, although the mutation did not affect the KDR D2D3 interaction with VEGF165. Since β3-knockout mice are known to show enhanced VEGF165 signaling, we propose that the binding of KDR D1 to the VEGF165 HBD and KDR D2D3 binding to the VEGF165 NTD are critically involved in the potent mitogenicity of VEGF165. We propose that binding competition between KDR and αvβ3 to the VEGF165 HBD endows integrin αvβ3 with regulatory properties to act as a negative regulator of VEGF165 signaling.

Degradation of TRIM32 is induced by RTA for Kaposi's sarcoma-associated herpesvirus lytic replication.

TRIM32 is associated with many cancers and viral infections; however, the role of TRIM32 in viral oncogenesis remains largely unknown. In this study, we found that the expression of TRIM32 is elevated by Kaposi's sarcoma-associated herpesvirus (KSHV) in latency, and RTA (the master regulator of lytic replication) induces TRIM32 for proteasome degradation upon viral lytic reactivation. This finding provides a potential therapeutic target for KSHV-associated cancers.

CD163+ macrophages in the triple-negative breast tumor microenvironment are associated with improved survival in the Women’s Circle of Health Study and the Women’s Circle of Health Follow-Up Study

BackgroundTumor-associated macrophages (TAMs) are a prominent immune subpopulation in the tumor microenvironment that could potentially serve as therapeutic targets for breast cancer. Thus, it is important to characterize this cell population across different tumor subtypes including patterns of association with demographic and prognostic factors, and breast cancer outcomes.MethodsWe investigated CD163+ macrophages in relation to clinicopathologic variables and breast cancer outcomes in the Women’s Circle of Health Study and Women’s Circle of Health Follow-up Study populations of predominantly Black women with breast cancer. We evaluated 611 invasive breast tumor samples (507 from Black women, 104 from White women) with immunohistochemical staining of tissue microarray slides followed by digital image analysis. Multivariable Cox proportional hazards models were used to estimate hazard ratios for overall survival (OS) and breast cancer-specific survival (BCSS) for 546 cases with available survival data (median follow-up time 9.68 years (IQR: 7.43–12.33).ResultsWomen with triple-negative breast cancer showed significantly improved OS in relation to increased levels of tumor-infiltrating CD163+ macrophages in age-adjusted (Q3 vs. Q1: HR = 0.36; 95% CI 0.16–0.83) and fully adjusted models (Q3 vs. Q1: HR = 0.30; 95% CI 0.12–0.73). A similar, but non-statistically significant, association was observed for BCSS. Macrophage infiltration in luminal and HER2+ tumors was not associated with OS or BCSS. In a multivariate regression model that adjusted for age, subtype, grade, and tumor size, there was no significant difference in CD163+ macrophage density between Black and White women (RR = 0.88; 95% CI 0.71–1.10).ConclusionsIn contrast to previous studies, we observed that higher densities of CD163+ macrophages are independently associated with improved OS and BCSS in women with invasive triple-negative breast cancer.Trial registrationNot applicable.

The use of photodynamic therapy in medical practice

Cancer therapy, especially for tumors near sensitive areas, demands precise treatment. This review explores photodynamic therapy (PDT), a method leveraging photosensitizers (PS), specific wavelength light, and oxygen to target cancer effectively. Recent advancements affirm PDT’s efficacy, utilizing ROS generation to induce cancer cell death. With a history spanning over decades, PDT’s dynamic evolution has expanded its application across dermatology, oncology, and dentistry. This review aims to dissect PDT’s principles, from its inception to contemporary medical applications, highlighting its role in modern cancer treatment strategies.

HER2 mutation as an emerging target in advanced breast cancer.

HER2 activating mutations have emerged as oncogenic drivers and therapeutic targets in a variety of human tumors. In breast cancer, these deregulations occur at low frequency, and are mostly detected in HER2-nonamplified, metastatic disease. Preclinical evidence has clarified the role of hotspot mutations in HER2 constitutive activation, defining them as an alternative mechanism to HER2 gene amplification. Furthermore, recent clinical studies have indicated the emergence of newly acquired HER2 deregulations in significant proportions of breast cancer patients who experience disease progression following both endocrine and HER2-targeted therapies. As the involvement of HER2 mutation in therapy resistance may profoundly impact patient outcomes on successive therapies, several clinical trials are currently investigating the efficacy of various HER2-targeted drugs in HER2-mutant breast cancer. In this review, we firstly summarize the structural organization of the HER2 oncogene and its historical impact on breast cancer prognosis and therapeutic advancement. Then, we provide an overview of the frequencies and functional relevance of clinically recurrent HER2 mutations in breast cancer with a special focus on their role in therapeutic resistance. Finally, we provide a collection of the clinical trials that are currently exploring novel therapeutic approaches for this patient subset and discuss the related perspectives and challenges.

GJB3: a comprehensive biomarker in pan-cancer prognosis and immunotherapy prediction.

A wide range of connexins are situated between normal-normal cells, cancer-cancer cells, and cancer-normal cells. Abnormalities in connexin expression are typically accompanied by cancer development; however, no systematic studies have examined the role of Gap Junction Protein Beta 3 (GJB3) in the context of tumor progression and immunity, especially when considering a broad range of cancer types. In this study, data on GJB3 expression were gathered from Genotype-Tissue Expression, Cancer Cell Line Encyclopedia, and The Cancer Genome Atlas databases. Then, we analyzed the relationship between GJB3 expression and tumor characteristics. In vitro experiments using colony formation, EdU, CCK8, transwell migration assays, immunohistochemistry and western blot were performed to investigate the function of GJB3 in tumor progression of various cell lines. A drug sensitivity analysis of GJB3 was performed using the Genomics of Drug Sensitivity in Cancer database. Our findings demonstrate that GJB3 is widely expressed in various cancers and correlates significantly with disease stages, patient survival, immunotherapy response, and pharmaceutical guidance. Additionally, GJB3 plays a role in different cancer pathways, as well as in different immune and molecular subtypes of cancer. Co-expression of GJB3 with immune checkpoint genes was observed. Further experiments showed that knockdown of GJB3 inhibited the PI3K/AKT pathway and resulted in reduced proliferation, migration, and viability of different cancer cells. Overall, GJB3 shows potential as a molecular biomarker and therapeutic target for various cancers, particularly lung adenocarcinomas, mesothelioma, pancreatic adenocarcinoma. Thus, GJB3 may represent a new therapeutic target for a wide range of cancers.

Mineral composition and heavy metal risk assesment of selected geophagic soils from Tanzania

Geophagy or Pica is the unintentional traditional behavior of eating soil by indigenous people in different countries. practiced in many countries due to nausea among pregnant women and mineral deficiencies without knowing the associated health risks. In this study the mineral composition of geophagic soil and its associated health risk among consumers was determined. Dry soil sticks consumed by women were obtained from open markets in Morogoro, Njombe and Mwanza regions in Tanzania. The elemental concentration of geophagic soil was analyzed using Flame Atomic Absorption spectrophotometer. Health risk assessment methods were used to obtain health information after chronic exposure to geophagic soils. The tests used were Target Hazard Quotients (THQ), Total Target Hazard Quotients (TTHQ) and Cancer Risks (CR). The concentration range of metals in samples obtained from three different regions were 16,335.7–47,773.7 mg/kg for Fe, 46.2–1073.5 mg/kg for Ca, 155.3–514.9 mg/kg for K, 44.5–112.4 mg/kg for Zn, 40.7–95.1 mg/kg for Na, 2.4–66.7 mg/kg for Cu, 109.5–572.6 mg/kg for Mn, 3.8–6.85 mg/kg for Pb, 3.1–93 mg/kg for Ni, 62.7–638.6 mg/kg for Cr and 0.4 mg/kg for Cd. The Provisional Daily Intake (PDI), THQ, TTHQ and CR ranged between 3.0 × 10−3 –34.12 mg/kg/day bw, 0.043–48.75, 34.52–77.36 and 2.55×10−5- 0.23 respectively. The TTHQ>1 was evident for metals in all sampling sites which is indicative of non-carcinogenic health effects. Prolonged exposure to Pb at low concentrations in samples from all the sites can cause pathological effects. The cancer risk values for Pb, Ni, Cr and Cd were <1 in which the consumer is likely not to develop cancer in a life time. Essential minerals – Fe, Ca, Zn, Na, K and toxic metals Pb, Cr, Ni and Cu were detected in all the samples. Cd occurred only in samples from Mwanza region that was below the tolerable daily intake. According to WHO/FAO expert’s joint committee any amount of Pb consumption is not permitted. Given the presence of essential minerals in the geophagic soils which are however accompanied by toxic minerals in some cases which might have carcinogenic effects, prolonged consumption should be discouraged to avoid risks of serious adverse effects to the health of the general population.

Unlocking the functional potential of Nitraria schoberi extracts using chemical fingerprinting, biological efficiencies, in silico and network pharmacological approaches

The objective of this investigation was to assess the cytotoxic, antioxidant, and enzyme inhibitory properties of the aerial portions of Nitraria schoberi (family Nitrariaceae). Extracts were prepared by sequential maceration in hexane, dichloromethane (DCM), ethyl acetate and methanol (MeOH) and water extract was prepared by infusion. DCM and MeOH extracts accumulated the highest amount of metabolites where the former was characterized by the presence of octadecyl ferulate (16.96 mg/100 mg), methoxyluteolin (8.48 mg/100 mg) and isorhamnetin (5.35 mg/100 mg) and the alkaloids perlolyrine (5.03 mg/100 mg), (+)-5a-hydroxylemannine (2.43 mg/100 mg) and matrine (2.40 mg/100 mg). Results of antioxidant activity showed that the MeOH extract exerted the highest anti-2,2-diphenyl-1-picrylhydrazyl (DPPH) (28.13 mg Trolox equivalent (TE)/g) and Fe+++ (54.38 mg TE/g) reducing capacity. All extracts exerted significant acetylcholinesterase (3.71–4.37 mg galantamine equivalent (GALAE)/g) and tyrosinase (86.40–109.63 mg kojic acid equivalent (KAE)/g) inhibition activity. The best α-amylase and α-glucosidase inhibition was exhibited by the DCM (0.81 mmol ACAE/g) and MeOH (1.34 mmol ACAE/g) extracts respectively. The highest cytotoxic effect was exerted against the breast adenocarcinoma (MDA-MB-231) (IC50: 26.71 μg/mL) and cervix adenocarcinoma (HELA) (IC50: 29.10 μg/mL) cell lines by the MeOH and DCM extracts respectively. In addition, we performed molecular docking analysis to understand the interaction between chemical components and tested enzymes and cellular targets for cancer. Chrysoeriol-3-O-rutinoside bound strongly to AChE. Furthermore, a good interaction between vascular endothelial growth factor receptor 2 (VEGFR2) and isovitexin-2″-O-arabinoside was observed. We employed network pharmacology to understand the role of N. schoberi's compounds in neurological disorder like Alzheimer and multiple sclerosis. Therefore, the results of this study indicate that N. schoberi may serve as a viable starting point for the future creation of phytopharmaceuticals that target particular diseases associated with oxidative stress, such as diabetes and certain neurological disorders.

AN UPDATED REVIEW OF STEALTH LIPOSOMES AND ITS ABILITY TO EVADE THE IMMUNE SYSTEM: A NEW FRONTIER IN CANCER CHEMOTHERAPY

Liposomes have been the delivery of choice for the cancer targeting therapy for the last few decades. Since the 1990s, the development of sterically stabilized (stealth) liposomes has garnered interest for their long circulating half-life. PEGylated (Polyethylene Glycol) liposomes are most extensively studied for delivering cancer therapeutics in a sustained manner. Stealth liposomes are having a less intrinsic toxicity with higher efficacy in cancer treatment. There are numerous clinical trials on the liposomes in tackling cancer is evident for the better outcome of the delivery system. Stealth liposomes are extensively studied for their improved circulation time and better pharmacokinetic profile in cancer treatment. The steric hindrance of the stealth liposomes bypasses the reticuloendothelial system clearance. Further the ligands conjugation in the surface of the liposomes able to achieve better target to the cancer cells. The vascularization nature of the cancerous cells is readily making the liposomal delivery of the cancer drugs accumulate in the cancerous cells rather than healthy cells. There is an utmost need to understand the possible mechanism of stealth liposomes and the basic science behind the development of liposomal delivery system in advancing the cancer treatment with less toxicity. The present review addresses the various modalities of the liposomal development, liposome characterization, mechanism of PEGylated liposomes, the advancements and results of the liposomes in the treatment of various diseases, and the clinical trials and regulatory considerations of liposomal drug delivery system.

The Inflammasome molecular machinery as a novel source of diagnostic, prognostic, and therapeutic targets in endocrine-related cancers

The Inflammasome molecular machinery as a novel source of diagnostic, prognostic, and therapeutic targets in endocrine-related cancers

Protease-activated receptor 2: a promising therapeutic target for women's cancers.

Cancers affecting women, such as breast, uterine, ovarian, endometrial and cervical cancers, have become increasingly prevalent. The growing incidence and death rates associated with these cancers warrant the development of innovative and alternative approaches to current treatments. This article investigates the association of women's cancers with a molecular target known as protease-activated receptor 2 (PAR2), a G-protein coupled receptor that is expressed on the surface of cancer cells. Expression levels of the PAR2 gene were curated from publicly available databases and were found to be significantly overexpressed in tissues from patients with breast, uterine, ovarian, endometrial or cervical cancer compared to normal tissues. PAR2 overexpression has been previously linked to tumor progression and, in some cases, tumor growth. Activation of PAR2 by either endogenous proteases or synthetic agonists triggers certain downstream intracellular signaling pathways that have been associated with tumor progression, cell migration and invasion, angiogenesis and apoptosis of cancer cells. While recent advances have led to the identification of several PAR2 antagonists, none has yet been developed for human use. Additionally, PAR2 inhibition has been shown also to increase the efficacy of chemotherapeutic drugs, allowing them to be potentially used at less toxic doses in combination therapies for cancer. The present work briefly summarizes the current status of PAR2 as a potential therapeutic target for treating women's cancers. Significance Statement This article highlights potential roles for PAR2 in cancers affecting women. Overexpression of the PAR2 gene in women's cancers is associated with various oncogenic processes such as tumor progression, cell migration and invasion, ultimately contributing to poorer patient prognoses. Given the increasing incidence of women's cancers, there is an urgent need to develop novel therapeutic drugs and PAR2 represents a promising target for developing new treatments.

Prognostic Value of B7H4 Expression in Patients with Solid Cancers: A Systematic Review and Meta-Analysis.

V-set domain-containing T-cell activation inhibitor 1 (aliases VTCN1, B7H4) participates in tumour immune escape by delivering inhibitory signals to T cells. The purpose of this article was to assess the B7H4 prognostic value in solid cancers. Three databases were searched for relevant articles. The main endpoints were overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS). Appropriate hazard ratios (HRs) were pooled. The R studio software (version 4.0.3) was used for data analysis. Thirty-one studies met the inclusion criteria. High expression of B7H4 was associated with worse OS (HR = 1.52, 95% CI: 1.37-1.68) but not with DSS (HR = 1.14, 95% CI: 0.49-2.63), RFS (HR = 1.77, 95% CI: 0.75-4.18), DFS (HR = 1.29, 95% CI: 0.8-2.09), or PFS (HR = 1.71, 95% CI: 0.91-3.2) in patients with solid cancers. High expression of B7H4 is associated with a poorer prognosis in patients with solid cancers. B7H4 is a promising prognostic biomarker and immunotherapeutic target for various solid cancers because of its activity in cancer immunity and tumourigenesis.

Expression of Potential Antibody-Drug Conjugate Targets in Cervical Cancer.

(1) Background: There is a huge unmet clinical need for novel treatment strategies in advanced and recurrent cervical cancer. Several cell membrane-bound molecules are up-regulated in cancer cells as compared to normal tissue and have revived interest with the introduction of antibody-drug conjugates (ADCs). (2) Methods: In this study, we characterize the expression of 10 potential ADC targets, TROP2, mesotheline, CEACAM5, DLL3, folate receptor alpha, guanylatcyclase, glycoprotein NMB, CD56, CD70 and CD138, on the gene expression level. Of these, the three ADC targets TROP2, CEACAM5 and CD138 were further analyzed on the protein level. (3) Results: TROP2 shows expression in 98.5% (66/67) of cervical cancer samples. CEACAM5 shows a stable gene expression profile and overall, 68.7% (46/67) of cervical cancer samples are CEACAM-positive with 34.3% (23/67) of cervical cancer samples showing at least moderate or high expression. Overall, 73.1% (49/67) of cervical cancer samples are CD138-positive with 38.8% (26/67) of cervical cancer samples showing at least moderate or high expression. (4) Conclusions: TROP2, CEACAM5 or CD138 do seem suitable for further clinical research and the data presented here might be used to guide further clinical trials with ADCs in advanced and recurrent cervical cancer patients.