Abstract 68P
Background
Chemoresistance remains a significant challenge in the treatment of gastric cancer, leading to poor prognosis and limited therapeutic options. The CCL5/CCR5 axis has been implicated in tumor progression and resistance to chemotherapeutics. Given the critical role of this axis in cancer progression, this study evaluated the potential of Maraviroc (MVC), a CCR5 antagonist, as an adjuvant to cisplatin (CDDP) to overcome chemoresistance in a murine model of gastric cancer.
Methods
A murine xenograft model using gastric tumor cells was employed. Tumoroids were formed from these cells and injected subcutaneously into immunocompromised BALB/c NOD/SCID mice. Animals were then randomized into four groups: a control group treated with saline, a group treated with maraviroc (MVC), a group treated with cisplatin (CDDP), and a group treated with a combination of MVC and CDDP. Tumor growth and survival were monitored for 21 days. Biochemical analyses were performed to assess the metabolic profile of the animals.
Results
The combination of MVC and CDDP did not induce a greater reduction in tumor volume compared to CDDP alone. However, the co-administration of MVC significantly improved the survival of treated animals (Figure 1). The combination MVC/CDDP attenuated the adverse effects of CDDP on biochemical parameters such as glucose, lactate, and creatinine levels.
Conclusions
The results suggest that MVC could act as a sensitizing agent, enhancing the efficacy of CDDP while reducing its toxicity. Although the exact mechanism of this synergy is not yet fully elucidated, it is hypothesized that blocking CCR5 could modulate the tumor immune response and reduce resistance to chemotherapy. These findings open new avenues for the development of combined therapeutic strategies for the treatment of gastric cancer. Future studies should delve deeper into the underlying molecular mechanisms and evaluate the efficacy of this combination in more complex preclinical models.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Agencia Nacional de Investigación y Desarrollo (ANID).
Disclosure
All authors have declared no conflicts of interest.