Emerging Protein Therapeutics as a Strategy for Cervical Cancer Treatment.

Cervical cancer continues to be a critical public health concern globally, with increasing mortality rates, particularly in Low- and Middle-Income Countries (LMICs) where healthcare resources remain limited. With more than 300,000 fatalities each year, it is the fourth most frequent cancer in women globally. Long-term infection with carcinogenic Human Papillomavirus (HPV) variants, which cause cancer through viral proteins including E5, E6, and E7, is the leading cause of cervical cancer. These proteins interfere with host cellular functions, which promote the development and spread of cancer. Conventional treatment strategies, including chemotherapeutics and immunotherapies, have achieved varying degrees of success. However, protein-based therapeutics have recently emerged as a promising class of agents in oncology due to their ability to modulate specific molecular targets with high precision and specificity. These biologics interact with cell surface receptors and orchestrate essential signalling cascades, such as the NF-κB, MAPK, and PI3K/AKT pathways. Notably, new classes of protein therapeutics, such as toxin-based agents and Bromodomain and Extra-Terminal (BET) domain inhibitors, have shown effectiveness in disrupting tumor-promoting pathways. In addition to their direct antitumor activities, protein therapeutics also modify the tumor microenvironment, affecting stromal elements and lymphatic architecture, and ultimately promoting apoptosis. This review critically examines the landscape of protein-based therapeutic approaches for cervical cancer, delineating their mechanisms of action and highlighting their role in targeting inflammatory pathways-such as inflammasomes and cytokine networks-that contribute to tumor progression and immune modulation.