
Finding The Right Biomarker for Cancer Research
Cancer has a major impact on society around the world and biomarkers play a pivotal role in cancer research. Leinco technologies brings you numerous resources for validating biomarkers against different cancer types and stages, discovering new biomarkers to improve diagnostics and drug development, identifying the impact biomarkers have on disease progression, and more. Take a look at the following list of cancer types and associated antibodies and proteins reported in applications.
Programmed Death-1 (PD-1) & Programmed Death-1 Ligand (PD-L1)
PD-L1 is a transmembrane protein that interacts with PD-1 to suppress lymphocyte activation and function, promote regulatory T cell responses, and impair anti-tumor T cell immune responses. PD-L1 is upregulated in non-small cell lung cancer (NSCLC) and correlates to the degree of tumor cell differentiation and metastasis1, suggesting its potential as a prognostic biomarker. PD-L1 is also a predictive biomarker, and IHC assays measure levels on lung cancer tissue to determine responsiveness to checkpoint inhibitors that target PD-1 or PD-L1. Tumor-infiltrating CD8+ T cells have increased PD-1 expression in patients with NSCLC, associated with impaired immune function2.
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Chen YB, Mu CY, Huang JA. Clinical significance of programmed death-1 ligand-1 expression in patients with non-small cell lung cancer: a 5-year-follow-up study. Tumori. 2012 Nov;98(6):751-5. doi: 10.1700/1217.13499. PMID: 23389362.
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Zhang Y, Huang S, Gong D, Qin Y, Shen Q. Programmed death-1 upregulation is correlated with dysfunction of tumor-infiltrating CD8+ T lymphocytes in human non-small cell lung cancer. Cell Mol Immunol. 2010 Sep;7(5):389-95. doi: 10.1038/cmi.2010.28. Epub 2010 May 31. PMID: 20514052; PMCID: PMC4002677.
Cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4)
CTLA-4 is a checkpoint protein present on the surface of activated T cells that negatively regulates T cell proliferation and T cell-mediated immune responses. CTLA-4 is expressed in NSCLC but not normal bronchial tissues and has prognostic value1,2. CTLA-4 expression on tumor cells contributes to tumorigenesis by increasing PD-L1 expression and cancer cell proliferation via the EGFR pathway2. Although anti-CTLA-4 antibodies, such as ipilimumab, are not effective treatments for NSCLC on their own, combination treatment with PD-1/PD-L1 inhibitors shows promise in PD-L1 positive NSCLC patients3.
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Salvi S, Fontana V, Boccardo S, Merlo DF, Margallo E, Laurent S, Morabito A, Rijavec E, Dal Bello MG, Mora M, Ratto GB, Grossi F, Truini M, Pistillo MP. Evaluation of CTLA-4 expression and relevance as a novel prognostic factor in patients with non-small cell lung cancer. Cancer Immunol Immunother. 2012 Sep;61(9):1463-72. doi: 10.1007/s00262-012-1211-y. Epub 2012 Feb 9. PMID: 22318401.
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Zhang H, Dutta P, Liu J, et al. Tumour cell-intrinsic CTLA4 regulates PD-L1 expression in non-small cell lung cancer. J Cell Mol Med. 2019;23(1):535-542. doi:10.1111/jcmm.13956
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Puri S, Shafique M. Combination checkpoint inhibitors for treatment of non-small-cell lung cancer: an update on dual anti-CTLA-4 and anti-PD-1/PD-L1 therapies. Drugs Context. 2020;9:2019-9-2. Published 2020 Jan 13. doi:10.7573/dic.2019-9-2
Vascular Endothelial Growth Factor (VEGF)
VEGF is a homodimeric glycoprotein that promotes angiogenesis in both physiological and pathological contexts, such as cancer1. VEGF contributes to lung cancer tumorigenesis through autocrine signaling, promoting epithelial-mesenchymal transition and invasiveness2. VEGF levels may be a useful diagnostic and prognostic biomarker for lung cancer, with relatively high sensitivity and specificity for NSCLC3.
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Ahluwalia A, Jones MK, Tarnawski AS. et al. Key role of endothelial importin-ɑ in VEGF expression and gastric angiogenesis: novel insight into aging gastropathy. Am J Physiol Gastrointest Liver Physiol. 2014;306:G338–45.
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Desai S, Laskar S, Pandey BN. Autocrine IL-8 and VEGF mediate epithelial-mesenchymal transition and invasiveness via p38/JNK-ATF-2 signalling in A549 lung cancer cells. Cell Signal. 2013 Sep;25(9):1780-91. doi: 10.1016/j.cellsig.2013.05.025. Epub 2013 May 25. PMID: 23714383.