Abstract

Dysregulation of cellular signaling pathways leads to changes in proliferation, differentiation, and apoptosis, leading to cancer. This review aims to provide insight into the major three signaling pathways implicated in cancer development and progression: the Hedgehog (Hh), Phosphoinositide 3-kinase (PI3K), and Notch pathways. Abnormal activation of the Hedgehog pathway, which has been linked to several malignancies, including medulloblastoma and basal cell carcinoma, is primarily responsible for controlling the phases of embryonic development and tissue homeostasis. The intricate involvement of Hh signaling in cancer stem cell maintenance, epithelial-mesenchymal transition, and tumor microenvironment modulation underscores its significance as a therapeutic target. Similarly, dysregulation of the PI3K pathway, a crucial mediator of cell growth, survival, and metabolism, is prevalent across multiple cancer types. Mutations in PI3K pathway components lead to uncontrolled cell proliferation and evasion of apoptosis, highlighting its potential as a therapeutic avenue. Various inhibitors targeting PI3K and its downstream effectors have shown promise in preclinical and clinical settings. Additionally, the Notch signaling pathway, crucial for cell fate determination and tissue patterning during development, exhibits dysregulated activity in numerous cancers. Notch pathway alterations contribute to tumor initiation, progression, and metastasis, presenting opportunities for targeted therapies. The review discusses current therapeutic strategies targeting these pathways, including small-molecule inhibitors, monoclonal antibodies, and combination therapies. Challenges, such as drug resistance and toxicity are addressed, along with emerging therapeutic approaches to enhance treatment efficacy. In conclusion, understanding the intricate crosstalk and dysregulation of signaling pathways in cancer provides valuable insights into disease mechanisms and therapeutic avenues, paving the way for more effective and personalized cancer treatments.

Keywords: Cancer, hedgehog pathway, mutation, phosphoinositide 3-kinase, notch pathway, combination therapy, apoptosis.