Mitochondrial Protease ClpP in Antitumor-Drug Development: Recent Advances and Challenges

Dear Colleagues,

Much of medicinal chemistry research on cancer focuses on targeted drugs that can specifically target tumor cells, sparing normal ones, thus having high potency and low toxicity. Particularly, small molecules as targeted drugs have advantages in pharmacokinetic properties, costs, patient compliance, and drug storage and transportation; thus, they are still undergoing significant development.

Cancer cells rely heavily on mitochondria to meet their high energy demands to fuel their rapid proliferation. Mitochondrial chaperone and protease proteins crucial for mitochondrial proteostasis are overexpressed in most tumor types, and are involved in metabolic reprogramming that allows for the evasion of apoptosis and increased survival.

Among the effectors of mitochondrial proteostasis, mitochondrial matrix serine proteases caseinolytic peptidase P (ClpP) is a key inducer of mitochondrial protein quality control for the clearance of misfolded or damaged proteins, which is necessary for maintaining mitochondrial functions. Elevated activities of ClpP are correlated with tumor development and progression. ClpP dysregulation has already been associated with many types of cancer localized in brain, breast, prostate, bladder, ovarian, gastric, colorectal, liver, lung, pancreatic and blood.

Small molecules that target ClpP by either inhibiting or dysregulating (activating) its function have been explored as potential anticancer drugs and could represent a novel approach in oncology.Authors are invited to submit original and review articles on the outcomes of their research that contribute to the understanding of ClpP as a potential therapeutic drug target in cancer. This Special Issue of Pharmaceuticals aims to bring together the research of experts working with ClpP to create a learning network that could increase knowledge on this mitochondrial serine protease, thus identifying future directions in cancer therapy. I look forward to your valuable contribution.

Dr. Maria Grazia Perrone
Dr. Morena Miciaccia
Guest Editors

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• caseinolytic peptidase P (ClpP)
• mitochondrial protein quality control
• small molecules as targeted drugs
• cancer therapy
• high-grade glioma
• breast cancer
• prostate adenocarcinoma
• hematological malignancies
• bladder cancer
• ovarian cancer