S-1 + oxaliplatin + olaparib

The combination of S-1, oxaliplatin, and olaparib represents a therapeutic approach that combines different mechanisms of action to target cancer cells. This combination includes a fluoropyrimidine antimetabolite (S-1), a platinum-based chemotherapy agent (oxaliplatin), and a PARP inhibitor (olaparib). ## Mechanism of Action This combination works through multiple pathways: 1. **Oxaliplatin** is a platinum-based chemotherapy agent that causes DNA damage through DNA crosslinking, particularly intrastrand and interstrand crosslinking[5]. It's commonly used to treat colorectal cancer and is typically administered in combination with fluorouracil and leucovorin (FOLFOX regimen)[5]. 2. **Olaparib** is a PARP (Poly ADP-ribose polymerase) inhibitor that blocks DNA repair mechanisms. Studies show that olaparib can increase the sensitivity of cancer cells to oxaliplatin by enhancing induced DNA double-strand breaks[2][3]. The combination of olaparib and oxaliplatin significantly increases cytotoxic effects compared to either agent alone[1][2]. 3. **S-1** is an oral fluoropyrimidine that combines tegafur (a prodrug of 5-fluorouracil) with two modulators. It's mentioned in the context of combination chemotherapy for advanced gastric cancer[1]. ## Research Findings Research has demonstrated that: - The combination of olaparib and oxaliplatin significantly reduces cell survival compared to oxaliplatin alone[1]. - This combination inhibits tumor cell proliferation by inducing cell cycle arrest and apoptosis, particularly in XRCC2-deficient colorectal cancer cells[2]. - The combined treatment increases DNA damage markers (γH2AX) compared to either drug alone[1][2][3]. - Olaparib changes the expression of PARP1 and enhances the sensitivity of cancer cells to oxaliplatin[1]. - The combination effectively inhibits the viability, size, cell count, and proliferation of organoids derived from oxaliplatin-resistant gastric cancers[3]. This triple combination represents a promising approach for treating various cancers, particularly those that have developed resistance to standard treatments.