Anticancer effects of PEP06 (TB01) in combination with Trifluridine/Tipiracil (TAS-102) in a xenograft model of human colorectal cancer

J Cancer Res Clin Oncol. 2024 Dec 26;151(1):22. doi: 10.1007/s00432-024-05984-z.

Abstract

Background: Colorectal cancer (CRC) is the third most common cancer globally, with advanced stages presenting significant treatment challenges. Recently years, drug combination therapy has become a promising strategy for cancer treatment.

Objective: To evaluate the therapeutic efficacy of the combination of the anti-angiogenic drug PEP06 (TB01) and the cytotoxic drug Trifluridine/Tipiracil (TAS-102) in human CRC HCT-116 xenograft mouse model. And quantitative assessment of the interaction between TB01 and TAS-102 in the treatment based on pharmacological effects.

Methods: This study utilized the human CRC HCT-116 xenograft nude mouse model to evaluate the antitumor effects of TAS-102 and TB01, both as mono-therapies and in combination therapies.

Results: The combination therapy not only demonstrated significantly inhibited tumor growth in a dose-dependent manner, but also seems to reduce the common toxicity associated with such treatments, as shown by the maintenance of body weights in the treated mice.

Conclusion: The synergistic effect observed from the combined use of TAS-102 and TB01 suggests a promising new treatment avenue for refractory CRC patients, meriting further investigation and potential clinical application.

Keywords: Colorectal cancer; Combination therapy; PEP06 (TB01); Synergistic effect; Trifluridine/Tipiracil (TAS-102).

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols* / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / pathology
  • Drug Combinations*
  • Drug Synergism
  • Female
  • HCT116 Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude*
  • Pyrrolidines* / administration & dosage
  • Pyrrolidines* / pharmacology
  • Pyrrolidines* / therapeutic use
  • Thymine* / pharmacology
  • Trifluridine* / administration & dosage
  • Trifluridine* / pharmacology
  • Trifluridine* / therapeutic use
  • Uracil* / analogs & derivatives
  • Uracil* / pharmacology
  • Uracil* / therapeutic use
  • Xenograft Model Antitumor Assays*

Substances

  • Trifluridine
  • Pyrrolidines
  • Thymine
  • trifluridine tipiracil drug combination
  • Drug Combinations
  • Uracil