Biomarker Research

Our medical research library holds 6 studies published in Biomarker Research (2015–2026). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 6 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: BioMed Central
• Published: 2013 to the present, England
• Language: English
• ISSN: 2050-7771 (electronic)
• Its record in the NLM Catalog

2020s

• First-in-human phase Ia study of the covalent TEAD palmitoylation inhibitor BPI-460372 in patients with advanced solid tumors: pharmacokinetics, exposure-limited dosing, and early antitumor activity. H. Liang, Y. Xu, J. Zhao, et al. 2026;14(1). PubMed · Publisher · Free full text

  Abstract

  Background: The Hippo pathway is a critical regulator of tumor development and progression, dysregulation of the Hippo pathway drives tumorigenesis in multiple malignancies. BPI-460,372 is a first‑in‑class covalent irreversible inhibitor of transcriptional enhanced associated domain (TEAD) palmitoylation. This first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of BPI-460,372 in patients with advanced solid tumors.

  Methods: This open-label, multicenter, single-arm phase Ia dose-escalation study enrolled patients with advanced solid tumors who had progressed after standard therapies or lacked available standard treatment options. A modified 3 + 3 design with accelerated titration was used. BPI-460,372 was administered orally once daily under fasting conditions, with dose escalation from 10 mg to 240 mg daily. Additional cohorts evaluated twice-daily dosing (80 mg and 120 mg) and postprandial administration (80 mg and 160 mg) to characterize exposure optimization strategies. Primary endpoints were safety, tolerability, dose-limiting toxicities (DLTs), and the maximum tolerated dose (MTD). Secondary endpoints included pharmacokinetics (PK) and preliminary antitumor efficacy. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; modified criteria were applied for malignant pleural mesothelioma.

  Results: Between April 2023 and December 2024, 36 patients were screened, and 28 patients were enrolled and treated. No DLTs were observed, and the MTD was not reached. All patients experienced at least one treatment-emergent adverse event (TEAE). Treatment-related adverse events (TRAEs) occurred in 89.3% of patients, with grade ≥ 3 events occurring in 39.3%. Proteinuria was the most common TRAE (46.4%, including 10.7% grade ≥ 3). Three deaths occurred during the study, including one treatment-related death due to abdominal infection. Pharmacokinetic analyses demonstrated rapid absorption, dose-dependent increases in exposure, achievement of steady-state exposure after repeated dosing, and limited drug accumulation. Among 28 evaluable patients, one confirmed partial response (PR) was observed in the 120 mg twice-daily cohort. The objective response rate (ORR) and disease control rate (DCR) were 3.6% (95% CI: 0.1-18.4) and 64.3% (95% CI: 44.1-81.4), respectively. Median progression-free survival (PFS) was 5.6 months (95% CI: 2.4-7.0), and median overall survival (OS) was 13.2 months (95% CI: 7.4-15.1).

  Conclusion: BPI-460,372 demonstrated a distinct pharmacokinetic profile and showed preliminary antitumor activity in patients with advanced solid tumors. However, treatment-emergent toxicities and exposure limitations constrained further dose escalation and prevented definition of an optimal biologically active dose. These findings support further clinical evaluation of BPI-460,372 using optimized dosing strategies, particularly in tumors with Hippo pathway dependency.

  Trial Registration: ClinicalTrials.gov NCT05789602. Registered on 29 March 2023.

  © 2026. The Author(s).

• Anti-Mesothelin CAR T cell therapy for malignant mesothelioma. L. Castelletti, D. Yeo, N. van Zandwijk, et al. 2021;9(1):11. Review PubMed · Publisher · Free full text

  Abstract

  Malignant mesothelioma (MM) is a treatment-resistant tumor originating in the mesothelial lining of the pleura or the abdominal cavity with very limited treatment options. More effective therapeutic approaches are urgently needed to improve the poor prognosis of MM patients. Chimeric Antigen Receptor (CAR) T cell therapy has emerged as a novel potential treatment for this incurable solid tumor. The tumor-associated antigen mesothelin (MSLN) is an attractive target for cell therapy in MM, as this antigen is expressed at high levels in the diseased pleura or peritoneum in the majority of MM patients and not (or very modestly) present in healthy tissues. Clinical trials using anti-MSLN CAR T cells in MM have shown that this potential therapeutic is relatively safe. However, efficacy remains modest, likely due to the MM tumor microenvironment (TME), which creates strong immunosuppressive conditions and thus reduces anti-MSLN CAR T cell tumor infiltration, efficacy and persistence. Various approaches to overcome these challenges are reviewed here. They include local (intratumoral) delivery of anti-MSLN CAR T cells, improved CAR design and co-stimulation, and measures to avoid T cell exhaustion. Combination therapies with checkpoint inhibitors as well as oncolytic viruses are also discussed. Preclinical studies have confirmed that increased efficacy of anti-MSLN CAR T cells is within reach and offer hope that this form of cellular immunotherapy may soon improve the prognosis of MM patients.

• Circulating long non-coding RNA GAS5 (growth arrest-specific transcript 5) as a complement marker for the detection of malignant mesothelioma using liquid biopsies. D.G. Weber, S. Casjens, A. Brik, et al. 2020;8:15. PubMed · Publisher · Free full text

  Abstract

  Background: For the detection of malignant mesothelioma additional markers are needed besides the established panel consisting of calretinin and mesothelin. The aim of this study was the identification and verification of long non-coding RNAs (lncRNAs) as complementing circulating markers.

  Methods: Candidate lncRNAs were identified in silico using previously published RNA expression profiles and verified using quantitative PCR (qPCR) in mesothelioma cell lines as well as human plasma samples from mesothelioma patients and asbestos-exposed controls.

  Results: GAS5 (growth arrest-specific transcript 5) as a single marker is marked by a low sensitivity of 14%, but the combination of GAS5 with calretinin and mesothelin increased the panel's sensitivity from 64 to 73% at a predefined specificity of 97%. Circulating GAS5 is not affected by pleurectomy before blood collection, age, or smoking status.

  Conclusions: GAS5 is verified as an appropriate circulating marker for the supplement of calretinin and mesothelin to detect malignant mesothelioma. Although the sensitivity of GAS5 is too low for the use as a single marker, the addition of GAS5 as a third marker improves the performance of the established marker panel. The benefit of GAS5 for the detection of malignant mesothelioma at early stages needs to be validated in a prospective study.

  © The Author(s) 2020.

• LOX family and ZFPM2 as novel diagnostic biomarkers for malignant pleural mesothelioma. M.K. Kim, H.W. Kim, M. Jang, et al. 2020;8:1. PubMed · Publisher · Free full text

  Abstract

  Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer that develops in the pleural and outer layer of tissues surrounding the lungs. MPM is primarily caused by occupational exposure to asbestos and results in a poor prognosis. Effective therapeutics as well as early diagnostics for the MPM are still lacking. To identify potential diagnostic biomarkers for MPM, we performed bioinformatics analysis of public database.

  Methods: Utilizing databases from Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO), we identified several potential candidates that could act as MPM biomarkers. We carried out additional molecular analyses of these potential markers using MPM patient tissue samples via quantitative polymerase chain reaction.

  Results: We identified Lysyl oxidase (LOX), Lysyl oxidase homologs 1&2 (LOXL1& LOXL2) Zinc Finger Protein, FOG Family Member 2 (ZFPM2) as potential diagnostic biomarkers for MPM. In this study, we found that the LOX family and ZFPM2 showed comparable diagnostic ability to Fibulin-3 or mesothelin (MSLN) and would be better potential biomarkers than Sulfatase 1 (SULF1), Thrombospondin 2 (THBS2) and Cadherin 11 (CDH11).

  Conclusions: LOX family and ZPFM2 were identified as novel MPM diagnostic biomarkers which could strengthen MPM clinical diagnostic capabilities.

  © The Author(s). 2020.

2010s

• Absence of calretinin protein expression in malignant mesotheliomas from asbestos-exposed NF2+/- mice and mouse mesothelioma cell lines from various mouse strains. W. Blum, T. Henzi, H.E. Châtel-Soulet, et al. 2018;6:19. PubMed · Publisher · Free full text

  Abstract

  Background: Calretinin is the most widespread positive marker for the immunohistochemical identification of malignant mesothelioma (MM) and was proposed to serve as a blood-based biomarker. Functionally, evidence has accumulated that calretinin might be implicated in MM tumorigenesis. We aimed to identify calretinin (CR; Calb2) in murine MM and reactive mesothelial cells in granuloma from asbestos-exposed NF2+/- mice, a line heterozygous for the tumor suppressor merlin (NF2), used as a mouse MM model. Additionally, we sought to ascertain the presence of calretinin in MM cell lines from other mouse strains. We also intended to investigate the role of calretinin in mesotheliomagenesis by comparing the survival of asbestos-exposed NF2+/- and NF2+/-CR-/- mice.

  Methods: NF2+/- and NF2+/-CR-/- mice, both lines on a C57Bl/6J background, were exposed to asbestos following an established protocol. Tumor histology and asbestos-induced mortality were assessed. MM and granuloma from NF2+/- mice were analyzed with immunohistochemical methods for calretinin expression. Levels of Calb2 mRNA and calretinin expression in tumors and MM cell lines of various mouse strains were determined by RT-qPCR and Western blot analysis, respectively.

  Results: No expression of calretinin at the protein level was detected, neither in MM from NF2+/- mice, NF2+/- MM-derived cell lines nor immortalized mesothelial cells of mouse origin. At the mRNA level we detected Calb2 expression in MM cell lines from different mouse strains. Survival of NF2+/- and NF2+/-CR-/- mice exposed to asbestos showed no significant difference in a log-rank (Kaplan-Meier) comparison.

  Conclusions: The concomitant determination of calretinin and mesothelin blood levels has been proposed for early detection of human MM. Mouse MM models based on asbestos exposure are assumed to yield helpful information on the time course of appearance of mesothelin and calretinin in the blood of asbestos-treated mice determining the earliest time point for interventions. However, the observed absence of calretinin in MM from NF2+/- mice and derived cell lines, as well as from MM cells from Balb/c and C3H mice likely precludes the use of calretinin as a biomarker for mouse MM. The results also indicate possible species differences with respect to an involvement of calretinin in the formation of MM.

• BAP1 hereditary cancer predisposition syndrome: a case report and review of literature. S. Klebe, J. Driml, M. Nasu, et al. 2015;3:14. Case report PubMed · Publisher · Free full text

  Abstract

  A 72-year-old woman was diagnosed with uveal melanoma, peritoneal mesothelioma and a primary biliary tract adenocarcinoma. She had a strong family history of mesothelioma as well as other malignancies including renal cell carcinoma. The recently described BAP1 hereditary cancer predisposition syndrome was suspected, but immunohistochemical labeling was not conclusive. Genetic testing confirmed a novel and unusual germline mutation in the ubiquitin hydrolase domain of the BAP1 gene (p.Tyr173Cys) and the patient was diagnosed with the BAP1 hereditary cancer predisposition syndrome. This case demonstrates the importance of clinically recognizing this rare syndrome and its manifestations, some which are still being characterized. It also highlights the importance of genetic testing in cases where there is a high clinical suspicion, even when screening tests, such as immunohistochemistry, in this case, are inconclusive. The diagnosis of a germline BAP1 mutation may have important implications for both the patient and their families with regards to further genetic testing and active surveillance programs. Further research is needed to fully understand the extent and clinical implications of this rare cancer syndrome.

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