Mesothelin as a biomarker for targeted therapy

Lv, Jiang

doi:10.1186/s40364-019-0169-8

Cited by 94 publications

(85 citation statements)

References 118 publications

(131 reference statements)

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“…antigen receptors (CAR) T cells have been developed and are believed to be promising therapeutics for patients with MSLN-expressing tumors (18). MSLN expression in immunohistochemistry is envisaged to be a suitable biomarker for predicting clinical response to these therapeutics, but its efficacy has never been fully evaluated.…”

Section: Diffuse Mesothelin Expression Leads To Worse Prognosis Throumentioning

confidence: 99%

“…Many anti-MSLN therapies such as a high-affinity chimeric monoclonal antibody (MORAb-009), recombinant immunotoxins (SS1P, RG7787/LMB-100), anti-MSLN antibody drug conjugates (anetumab ravtansine, DMOT4039A, BMS-986148), or adoptive T-cell immunotherapy using MSLN-specific CARs in autologous T lymphocytes are currently being investigated in phase I and II studies targeting advanced solid tumors including pancreatic cancer and malignant mesothelioma with high MSLN expression (18). In the present study, over half of the CRC patients showed tumor-specific MSLN expression.…”

Section: % CI -------------------------------------------------Varimentioning

confidence: 99%

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Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer

et al. 2020

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Mesothelin (MSLN) is a glycophosphatidylinositol (GPI)-linked cell surface protein that is highly expressed in several types of malignant tumor, including malignant pleural mesothelioma, ovarian cancer and pancreatic adenocarcinoma. Recently, a comprehensive immunohistochemical study using MN-1 monoclonal antibody identified a significant number of colorectal tumors in which MSLN was expressed. However, the clinicopathological profiles and survival of patients with MSLN-positive colorectal cancer have not been fully analyzed. In the current study, the expression of MSLN in 270 primary and 44 metastatic colorectal tumors was immunohistochemically analyzed to determine the clinical usefulness of MSLN immunohistochemistry and to identify potential candidates for future anti-MSLN therapy. In vitro experiments using colon cancer cell lines were performed to investigate the biological significance of MSLN expression in tumors. The results of univariate analyses identified a significant correlation between MSLN expression and females (P=0.0042). Furthermore, an inverse correlation between MSLN expression and solid/sheet-like proliferation (P= 0.014) was also revealed. Additionally, overall survival was significantly shorter in patients with diffuse luminal/membranous expression of MSLN (P=0.018). Multivariable Cox hazards regression analysis revealed diffuse MSLN expression (hazard ratio, 2.26; 95% confidence interval, 1.04-4.91; P= 0.039) as a potential risk factor. When comparing primary CRCs and the metastasis of each, a weakly positive correlation was identified for MSLN positivity (% positive cells; R=0.484; P<0.0001). The in vitro experiments revealed a positive role for MSLN in colon cancer cell proliferation. Thus, MSLN immunohistochemistry may be useful in the prognostication of patients with CRC. The results demonstrated that significant numbers of patients with MSLN-positive CRC exhibiting metastasis could be targeted by anti-MSLN therapies.

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Section: Diffuse Mesothelin Expression Leads To Worse Prognosis Throumentioning

confidence: 99%

Section: % CI -------------------------------------------------Varimentioning

confidence: 99%

Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer

et al. 2020

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“…MSLN is a glycoprotein expressed more on the cell surface of several tumors, including MPM cells, than in normal tissues (111). A phase II clinical trial (NCT00738582) testing amatuximab, a chimeric anti-MSLN mAb, plus standard CT compared to CT alone showed a promising OS of 14.8 months (112) that was not confirmed in the ARTEMIS trial (NCT02357147).…”

Section: Mesothelioma Targeting Antigensmentioning

confidence: 99%

Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future

et al. 2020

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Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the pleural surface associated with asbestos exposure. The median survival of MPM patients is a mere 8-14 months, and there are few biomarkers and no cure available. It is hoped that, eventually, the incidence of MPM will drop and remain low and constant, given that most nations have banned the use of asbestos, but in the meantime, the incidence in Europe is still growing. The exact molecular mechanisms that explain the carcinogenicity of asbestos are not known. Standard therapeutic strategies for MPM include surgery, often coupled with chemotherapy and/or radiotherapy, in a small percentage of eligible patients and chemotherapy in tumors considered unresectable with or without adjuvant radiotherapy. In recent years, several new therapeutic avenues are being explored. These include angiogenesis inhibitors, synthetic lethal treatment, miRNA replacement, oncoviral therapies, and the fast-growing field of immunotherapy alone or in combination with chemotherapy. Of particular promise are the multiple options offered by immunotherapy: immune checkpoint inhibitors, tumor vaccines, and therapies taking advantage of tumor-specific antigens, such as specific therapeutic antibodies or advanced cell-based therapies exemplified by the CART cells. This review comprehensively presents both old and new therapeutic options in MPM, focusing on the results of the numerous recent and ongoing clinical trials in the field, including the latest data presented at international meetings (AACR, ASCO, and ESMO) this year, and concludes that more work has to be done in the framework of tailored therapies to identify reliable targets and novel biomarkers to impact MPM management.

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“…A more detailed overview of anti-MSLN antibody-based drugs and vaccines can be found in a recent review by Lv J. & Li P [68].…”

Section: Anti-msln Cancer Vaccinesmentioning

confidence: 99%

Mesothelin-targeted CAR-T cell therapy for solid tumors

Klampatsa

Dimou

Albelda

2020

Expert Opinion on Biological Therapy

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Mesothelin as a biomarker for targeted therapy

Cited by 94 publications

References 118 publications

Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer

Diffuse mesothelin expression leads to worse prognosis through enhanced cellular proliferation in colorectal cancer

Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future

Mesothelin-targeted CAR-T cell therapy for solid tumors

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