Molecular carcinogenesis and genetic insights in leiomyosarcoma: involvement of PI3K/AKT/mTOR/MAPK/ERK pathway

One of the most common soft-tissue sarcomas is LMS, a highly aggressive mesenchymal malignancy. LMS is characterized by significant molecular and clinical heterogeneity, arising from diverse anatomical sites and exhibiting distinct genomic alterations across subtypes. Among the key oncogenic drivers, the PI3K/AKT/mTOR signaling pathway plays a central role in regulating cell growth, proliferation, and survival. Dysregulation of this pathway, often through PTEN loss or upstream receptor activation, has been increasingly implicated in the pathogenesis of LMS, making it a critical therapeutic target. The MAPK pathway is among other intracellular signaling pathways and is significant in processes such as cell proliferation, differentiation, apoptosis, angiogenesis, and tumor metastasis. The important MAPK cascades found in eukaryotic cells include ERK, JNK/stress-activated protein kinase, p38 MAPK, and ERK5 signaling pathways. As these pathways are critical, they are promising areas for cancer therapy. In short, attention is on translating PI3K/AKT inhibitors into clinical practice to provide patients with new targeted therapy. This review summarizes the molecular mechanisms underlying LMS pathogenesis and discusses emerging therapeutic strategies to improve clinical outcomes.