Progastrin: An Overview of Its Crucial Role in the Tumorigenesis of Gastrointestinal Cancers

TL;DR

This paper reviews progastrin's role in gastrointestinal cancer development and its potential as a biomarker for diagnosis and treatment.

Contribution

The paper provides a comprehensive overview of progastrin's molecular mechanisms and clinical relevance in gastrointestinal cancers.

Findings

Progastrin is a detectable circulating protein (hPG80) in cancer that may promote cell proliferation.

Progastrin's interaction with immune pathways could influence cancer progression and treatment outcomes.

Progastrin shows potential as a diagnostic and prognostic biomarker for gastrointestinal cancers.

Abstract

Defining predictive biomarkers for targeted therapies and optimizing anti-tumor immune response is a main challenge in ongoing investigations. Progastrin has been studied as a potential biomarker for detecting and diagnosing various malignancies, and its secretion has been associated with cell proliferation in the gastrointestinal tract that may promote tumorigenesis. Progastrin is a precursor molecule of gastrin, synthesized as pre-progastrin, converted to progastrin after cleavage, and transformed into amidated gastrin via biosynthetic intermediates. In cancer, progastrin does not maturate in gastrin and becomes a circulating and detectable protein (hPG80). The development of cancer is thought to be dependent on the progressive dysregulation of normal signaling pathways involved in cell proliferation, thus conferring a growth advantage to the cells. Understanding the interaction between progastrin and the immune system is essential for developing future cancer strategies. To that end, the present review will approach the interlink between gastrointestinal cancers and progastrin by exploring the underlying molecular steps involved in the initiation, evolution, and progression of gastrointestinal cancers. Finally, this review will focus on the clinical applications of progastrin and investigate its possible use as a diagnostic and prognostic tumor circulating biomarker for disease progression and treatment effectiveness, as well as its potential role as an innovative cancer target.

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