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Pure substances consist of only one type of matter. A pure substance can be an element or a compound. An element consists of only one type of atom, while a compound consists of two or more types of atoms held together by a chemical bond.
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Pure substances consist of only one type of matter. A pure substance can be an element or a compound. An element consists of only one type of atom, while a compound consists of two or more types of atoms held together by a chemical bond. Elements are classified as atomic or molecular based on the nature of their basic units.
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In most main group element compounds, the valence electrons of the isolated atoms combine to form chemical bonds that satisfy the octet rule. For instance, the four valence electrons of carbon overlap with electrons from four hydrogen atoms to form CH4. The one valence electron leaves sodium and adds to the seven valence electrons of chlorine to form the ionic formula unit NaCl (Figure 1a). Transition metals do not normally bond in this fashion. They primarily form coordinate covalent bonds, a...
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Compound Library Screening Identified Cladribine as a Novel Radiosensitizer for Prostate Cancer.

Toshiki Oka1, Koji Hatano1, Shohei Katsuki2

  • 1Department of Urology, The University of Osaka Graduate School of Medicine, Suita, Osaka, Japan.

Cancer Science
|January 20, 2026
PubMed
Summary

This study identified cladribine as a potent radiosensitizer for prostate cancer treatment. A high-throughput screening platform found cladribine enhances radiation therapy effectiveness by preventing DNA repair in cancer cells.

Keywords:
cladribinecompound library screeningprostate cancerradiationradiosensitizer

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Area of Science:

  • Oncology
  • Radiotherapy
  • Drug Discovery

Background:

  • Prostate cancer recurrence after radiation therapy necessitates improved treatment strategies.
  • Enhancing tumor radiosensitivity is crucial for overcoming treatment resistance.
  • Drug repurposing offers a pathway to identify novel radiosensitizers.

Purpose of the Study:

  • To develop and utilize a high-throughput drug repurposing platform to identify FDA-approved compounds that enhance radiosensitivity in prostate cancer.
  • To validate candidate radiosensitizers in vitro and in vivo.
  • To investigate the mechanism of action of identified radiosensitizers.

Main Methods:

  • A library of 1134 FDA-approved compounds was screened using a luciferase-based assay in LNCaP prostate cancer cells.
  • Primary and secondary screening identified candidate radiosensitizers at various drug concentrations and radiation doses.
  • In vitro efficacy was assessed in multiple prostate cancer cell lines, and in vivo efficacy was evaluated in xenograft models.

Main Results:

  • The screening platform identified several candidate radiosensitizers, with cladribine emerging as the most potent.
  • Cladribine significantly increased radiation-induced cytotoxicity in prostate cancer cell lines (22Rv1, DU145, PC3) with dose-modifying factors ranging from 1.43 to 1.55.
  • Cladribine inhibited the repair of radiation-induced DNA double-strand breaks, evidenced by increased γH2AX levels.
  • The radiosensitizing effect of cladribine was confirmed in vivo using prostate cancer xenograft models.

Conclusions:

  • A luciferase-based high-throughput drug repurposing platform effectively identifies clinically relevant radiosensitizers.
  • Cladribine demonstrates significant radiosensitizing potential in prostate cancer cells, both in vitro and in vivo.
  • Cladribine is a promising candidate for further translational research to improve prostate cancer radiotherapy outcomes.