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Cancer or model
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Klotho intervention
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Main preclinical finding
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Evidence level
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|---|---|---|---|
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Breast cancer
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Increased α-Klotho expression or administered its KL1 domain
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Reduced cancer cell growth; administered KL1 slowed growth of MDA-MB-231 tumors implanted in mice.
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Cells and mouse tumors
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Pancreatic cancer
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α-Klotho or KL1 protein; gene delivery of a soluble Klotho form
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Reduced pancreatic cancer growth in cell and mouse models. A separate genetically engineered mouse study supported a tumor suppressor role for Klotho.
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Cells and multiple mouse models
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Colorectal cancer
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Soluble α-Klotho, KL1, or increased Klotho expression
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Reduced colony formation and tumor growth in mouse models. In another study, administered Klotho weakened the tumor promoting effect of senescent stromal cells.
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Cells and mouse tumors
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Lung cancer and metastasis
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Administered secreted α-Klotho; altered Klotho expression
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Secreted Klotho suppressed metastatic colonization in mice. Cell studies found reduced growth or movement and increased apoptosis; a separate study examined cisplatin sensitivity. These are different outcomes and should be reported separately.
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Cells and mouse metastasis model
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Liver cancer
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Increased α-Klotho expression or soluble protein
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Reduced hepatocellular carcinoma cell growth and tumor growth in mice, alongside changes in Wnt/β-catenin signaling.
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Cells and mouse tumors
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Osteosarcoma
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Increased α-Klotho expression in tumor cells
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Reduced primary tumor growth and pulmonary metastasis in a mouse model.
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Mouse tumors
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Diffuse large B-cell lymphoma
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Increased α-Klotho expression in lymphoma cells
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Reduced tumor volume in mice, with lower tumor proliferation markers; the study investigated IGF-1 receptor signaling.
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Cells and mouse tumors
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Papillary thyroid cancer with a RET fusion
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Increased α-Klotho expression
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Suppressed tumor growth and increased apoptosis in mice; the study investigated Wnt/β-catenin signaling.
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Cells and mouse tumors
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Melanoma
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Reduced α-Klotho expression
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Klotho loss increased xenograft growth. This supports a protective role in that model but does not test administered Klotho as therapy.
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Mouse tumor; loss-of-function
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Liver and non-small-cell lung cancer: β-Klotho
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Increased β-Klothoexpression
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Reduced tumor growth in the models studied. β-Klotho has different biology from α-Klotho, so these findings cannot be used as direct evidence for an α-Klotho product.
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Mouse tumors; different protein
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What the data support: α-Klotho has shown tumor suppressing activity across several cell and mouse models, with direct protein administration tested in some models. Preclinical studies support investigation of Klotho as a potential anticancer approach.

