Bruton’s Tyrosine Kinase: A Double-Edged Sword in Cancer and Aging

Bruton’s tyrosine kinase (BTK) is a key signaling molecule involved in both hematological malignancies and solid tumors. In B-cell malignancies such as chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), BTK mediates B-cell receptor signaling, promoting tumor survival and proliferation, leading to the development of BTK inhibitors like ibrutinib that improve patient outcomes. In solid tumors, BTK isoforms, particularly p65BTK, contribute to tumor growth and therapy resistance, with inhibition showing promise in cancers like colorectal, ovarian, and non-small cell lung cancer. BTK also influences the tumor microenvironment by modulating immune cells such as myeloid-derived suppressor cells and tumor-associated macrophages, aiding immune evasion. BTK inhibition can enhance anti-tumor immunity and reduce inflammation-driven tumor progression. Additionally, BTK contributes to tumor angiogenesis, with inhibitors like ibrutinib showing anti-angiogenic effects. Beyond cancer, BTK is linked to aging, where its modulation may reduce senescent cell accumulation and preserve cognitive function. This review explores BTK’s dual role, focusing on its oncogenic effects and potential impact on aging processes. We also discuss the use of BTK inhibitors in cancer treatment and their potential to address age-related concerns, providing a deeper understanding of BTK as a therapeutic target and mediator in the complex relationship between cancer and aging.