Targeting vulnerability in tumor therapy: Dihydroorotate dehydrogenase

Area of Science:

• Biochemistry
• Oncology
• Molecular Biology

Background:

• Dihydroorotate dehydrogenase (DHODH) is a critical enzyme in the de novo pyrimidine biosynthesis pathway.
• DHODH plays a significant role in regulating tumor metabolism, cell fate, and oncogenic signaling.
• It is increasingly recognized as a key therapeutic target in various cancer types.

Purpose of the Study:

• To review the multifaceted roles of DHODH in cancer, including its structural features, metabolic regulation, and involvement in oncogenic signaling.
• To analyze the efficacy and challenges of DHODH inhibitors in preclinical and clinical cancer studies.
• To propose future research directions for overcoming barriers in the clinical application of DHODH-targeted tumor therapies.

Main Methods:

• Literature review focusing on DHODH's role in tumor metabolism, signaling, and drug resistance.
• Analysis of preclinical data on DHODH inhibitors in various cancer models.
• Evaluation of clinical trial outcomes and challenges associated with DHODH inhibitors.

Main Results:

• DHODH's unique structure facilitates diverse biological functions, controlling tumor metabolism and cell fate.
• DHODH acts as a metabolic-signaling hub, activating oncogenic signals, promoting metastasis, and mediating drug resistance.
• DHODH inhibitors demonstrate significant efficacy in preclinical tumor models.

Conclusions:

• DHODH is a vital target in oncology due to its central role in tumor metabolism and signaling.
• Clinical translation of DHODH inhibitors is hindered by drug-related limitations and external constraints.
• Future research must address these challenges to establish a systematic framework for DHODH-targeted cancer therapy.