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An Integrative Approach to Lung Cancer Therapy: Linking the TGF-β (+869 C/T) Polymorphism to a Structurally Validated

Nawar Bahaa Abdulsahib1, Mohammed A Hameed2, Ragheed Hussam Yousif1

  • 1Department of Biotechnology, College of Applied Sciences, University of Technology, Baghdad, Iraq.

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Summary

This study links the TGF-β pathway, its genetic polymorphism, and lung cancer risk in Iraq. Quercetin shows promise as an ALK5 inhibitor, offering potential new therapeutic avenues.

Keywords:
ALK5 / TGF-β Receptor 1Lung cancerMolecular dockingTGFB1 Polymorphism

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Area of Science:

  • Biochemistry and Molecular Biology
  • Genetics
  • Oncology

Background:

  • The transforming growth factor-beta (TGF-β) pathway plays a crucial role in cellular processes, and its dysregulation is implicated in various diseases, including cancer.
  • Genetic variations within the TGF-β pathway, such as the TGF-β1 (+869 C/T) polymorphism, may influence individual susceptibility to diseases like lung cancer.

Purpose of the Study:

  • To establish a genetic and clinical roadmap for the TGF-β pathway in an Iraqi population concerning lung cancer.
  • To identify potential therapeutic agents targeting the TGF-β pathway, specifically its receptor ALK5.

Main Methods:

  • Utilized a structure-guided approach to identify quercetin as a potential ALK5 inhibitor.
  • Assessed biochemical profiles by measuring serum TGF-β and IL-17 levels.
  • Genotyped the TGF-β1 (+869C/T) polymorphism using ARMS-PCR.
  • Performed molecular docking to study quercetin-ALK5 interactions.

Main Results:

  • Elevated serum TGF-β and IL-17 levels were observed in lung cancer patients compared to healthy controls (P < 0.05).
  • The TGF-β1 (+869 C/T) polymorphism showed a genetic predisposition, with the 'TT' genotype associated with higher lung cancer risk.
  • Molecular docking confirmed quercetin's binding to ALK5 via key hydrogen bonds with hinge residues.

Conclusions:

  • A significant association exists between TGF-β pathway activity, the +869C/T polymorphism, and lung cancer susceptibility in the Iraqi population.
  • Quercetin demonstrates potential as a natural inhibitor of ALK5, warranting further investigation for lung cancer treatment.