Klotho and cancer: preclinical study summary

Cancer or model Klotho intervention Main preclinical finding Evidence level Breast cancer Increased α-Klotho expression or administered its KL1 domain…
Lionheart health bioelectric cancer research
Cancer or model
Klotho intervention
Main preclinical finding
Evidence level
Breast cancer
Increased α-Klotho expression or administered its KL1 domain
Reduced cancer cell growth; administered KL1 slowed growth of MDA-MB-231 tumors implanted in mice.
Cells and mouse tumors
Pancreatic cancer
α-Klotho or KL1 protein; gene delivery of a soluble Klotho form
Reduced pancreatic cancer growth in cell and mouse models. A separate genetically engineered mouse study supported a tumor suppressor role for Klotho.
Cells and multiple mouse models
Colorectal cancer
Soluble α-Klotho, KL1, or increased Klotho expression
Reduced colony formation and tumor growth in mouse models. In another study, administered Klotho weakened the tumor promoting effect of senescent stromal cells.
Cells and mouse tumors
Lung cancer and metastasis
Administered secreted α-Klotho; altered Klotho expression
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.
Cells and mouse metastasis model
Liver cancer
Increased α-Klotho expression or soluble protein
Reduced hepatocellular carcinoma cell growth and tumor growth in mice, alongside changes in Wnt/β-catenin signaling.
Cells and mouse tumors
Osteosarcoma
Increased α-Klotho expression in tumor cells
Reduced primary tumor growth and pulmonary metastasis in a mouse model.
Mouse tumors
Diffuse large B-cell lymphoma
Increased α-Klotho expression in lymphoma cells
Reduced tumor volume in mice, with lower tumor proliferation markers; the study investigated IGF-1 receptor signaling.
Cells and mouse tumors
Papillary thyroid cancer with a RET fusion
Increased α-Klotho expression
Suppressed tumor growth and increased apoptosis in mice; the study investigated Wnt/β-catenin signaling.
Cells and mouse tumors
Melanoma
Reduced α-Klotho expression
Klotho loss increased xenograft growth. This supports a protective role in that model but does not test administered Klotho as therapy.
Mouse tumor; loss-of-function
Liver and non-small-cell lung cancer: β-Klotho
Increased β-Klothoexpression
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.
Mouse tumors; different protein
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.