Protein tyrosine phosphatase 1B in solid tumors: Unraveling its clinical significance

The protein tyrosine phosphatase 1B (PTP1B) participates in diseases such as cardiometabolic disorders and malignancies. We investigated in depth the expression and clinical significance of PTP1B in various solid tumors. The PTP1B clinical duality is evident. In HER2-positive breast cancer, gastric cancer, and non-small cell lung cancer, PTP1B often acts as an oncogene, which is linked to more advanced disease, more metastasis, and a worse prognosis. In breast cancer with ER+ and some kidney cancers, PTP1B works as a tumor suppressor, which is associated with better survival and a better response to treatment. This duality emphasizes that PTP1B's involvement in cancer is not specific and does determines specific clinical outcomes or therapeutic responses. We also analyzed how PTP1B can halt tumor growth by affecting pathways like PI3K/Akt and JAK/STAT, but it can also promote tumor growth by activating pathways like EGFR, RAS-MAPK, and Src signaling. We examined the existing landscape of PTP1B inhibitors, highlighting ongoing deficiencies in efficacy, selectivity, and bioavailability that have led to clinical failures. Ultimately, a better understanding of the mechanisms underlying PTP1B expression and its context-dependent influencing tumor behavior is crucial for advancing of cancer prevention and treatment, especially for patients with metabolic risk factors.