oxaliplatin

Overview

Oxaliplatin is a platinum-based chemotherapeutic agent used primarily in the treatment of gastrointestinal malignancies, especially colorectal and gastric cancers. It is a third-generation platinum compound and is structurally distinct from cisplatin and carboplatin, with a broader clinical role in combination regimens such as fluorouracil/leucovorin-based therapy, capecitabine plus oxaliplatin (CapeOX or XELOX), and oxaliplatin-containing multi-drug protocols.

Biologically, oxaliplatin exerts antitumor activity through platinum-DNA adduct formation, leading to DNA damage, replication stress, and cell death. In recent research, it has also been studied in relation to resistance mechanisms, immunogenic cell death, ferroptosis, autophagy, and tumor microenvironment remodeling. These studies reflect its continuing importance not only as a standard cytotoxic drug, but also as a reference compound in investigations of combination therapy, drug delivery systems, and mechanisms of chemotherapy resistance.

Focus of Latest Publications

Recent publications on oxaliplatin have focused on its role in combination therapy, resistance biology, and mechanisms of action across gastrointestinal cancers. In colorectal cancer models, oxaliplatin was shown to induce nucleolar stress, suppress nascent rRNA synthesis, and activate p53 signaling, with these responses reduced in oxaliplatin-resistant cells. Related work also reported that oxaliplatin can induce both genotoxic damage and reactive oxygen species production in HCT116 colorectal cancer cells, with similar effects observed in TP53 wild-type and TP53-null cells under the tested non-cytotoxic conditions. Together, these studies reinforce oxaliplatin’s ability to trigger stress-response pathways linked to DNA damage, oxidative stress, and ribosome biogenesis disruption.

Several studies examined strategies to overcome oxaliplatin resistance or enhance its antitumor activity. Artesunate was reported to reverse oxaliplatin resistance in colorectal cancer by inducing ferroptosis through inhibition of the CDK5/Nrf2/GPX4 pathway, and RAD1 was identified as a promoter of oxaliplatin resistance in gastric cancer by reinforcing NRF2-driven antioxidant defense and DNA damage response checkpoint signaling. In gastric cancer, oxaliplatin was also incorporated into biomimetic adhesive hydrogel microspheres with polydopamine and nitric oxide donors for combined photothermal therapy, gas therapy, and chemotherapy, producing strong antitumor effects in vitro and in vivo with minimal systemic side effects. Another nanoparticle platform co-delivered oxaliplatin and fruquintinib to induce immunogenic cell death and remodel the tumor microenvironment in colorectal cancer, while thermosensitive nanogel and supramolecular carrier studies aimed to improve local retention and controlled release of oxaliplatin.

Clinical and translational studies further evaluated oxaliplatin in perioperative, adjuvant, and chemoimmunotherapy settings. A randomized phase 3 trial and a real-world cohort study in gastric or gastro-oesophageal junction adenocarcinoma assessed capecitabine/oxaliplatin-based regimens, including combinations with camrelizumab, while a case report described pharmacokinetic and pharmacogenomic considerations for capecitabine plus oxaliplatin in a patient with gastric cancer undergoing hemodialysis. In colorectal and liver metastasis settings, postoperative hepatic arterial infusion of oxaliplatin after resection of multiple colorectal liver metastases and neoadjuvant oxaliplatin-containing regimens were investigated for efficacy and safety. Oxaliplatin was also studied in older patients with stage III or high-risk stage II colon cancer, and in gastric cancer chemoimmunotherapy where capecitabine/oxaliplatin was paired with pembrolizumab, with early changes in circulating myeloid cells associated with clinical response.

Additional publications explored oxaliplatin in supportive care and localized delivery contexts. In a rat model of oxaliplatin-induced cognitive impairment, thymol nanoparticles mitigated behavioral and biochemical changes linked to Nrf2/HO-1 signaling, endoplasmic reticulum stress, and NLRP3 inflammasome activation, without reducing oxaliplatin’s cytotoxicity in colorectal cancer cell lines. In peritoneal metastasis models, localized macrophage depletion by abdominal cavity retention nanoparticles synergized with oxaliplatin to prolong survival in mice bearing colorectal peritoneal metastases. Oxaliplatin was also evaluated in a hemodialysis patient with gastric cancer, and in a theoretical supramolecular chemistry study showing competitive binding preferences relevant to biomarker-triggered drug displacement.

Key Publications

• NEWJun A nucleolar stress gene signature enables quantitative scoring across multi-omics contexts. (Communications biology, 2026, PMID 42373768): "Using this framework, we show in colorectal cancer models that oxaliplatin induces nucleolar stress, suppresses nascent rRNA synthesis, and activates p53 signaling, whereas these responses are attenuated in oxaliplatin-resistant cells."
• NEWJun Biomimetic adhesive hydrogel microcarriers for gas therapy and chemotherapy of gastric cancer. (Acta biomaterialia, 2026, PMID 42285389): "biomimetic adhesive hydrogel microspheres (MSs) encapsulated with NO donors (S-nitrosoglutathione, GSNO), polydopamine (PDA) nanoparticles, and a chemotherapeutic agent (Oxaliplatin, OXA) were fabricated for gastric cancer combination therapy."
• Jun Localized Depletion of Macrophages by Abdominal Cavity Retention Nanoparticles as a Potential Therapy for Peritoneal Metastasis. (ACS nano, 2026, PMID 42225301): "...the macrophage depletion induced by Clodro-LNP-L synergizes with the first-line chemotherapy drug oxaliplatin (OXP) to prolong the overall survival of mice bearing colorectal PM."
• May RAD1 promotes oxaliplatin resistance in gastric cancer by reinforcing NRF2-driven antioxidant defense and DDR checkpoint signaling. (Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy, 2026, PMID 42217457): "Resistance to oxaliplatin treatment limits therapeutic benefit in gastric cancer (GC) and remains difficult to predict from bulk biomarkers."
• May Thymol nanoparticles ameliorate oxaliplatin-induced cognitive impairment via modulation of Nrf2/HO-1, endoplasmic reticulum stress, and NLRP3 inflammasome signaling in rats. (Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2026, PMID 42202464): "Platinum-based chemotherapeutic agents, such as oxaliplatin (OXA), are effective in the treatment of colorectal cancer."
• May Artesunate overcomes oxaliplatin resistance in colorectal cancer by inducing ferroptosis through inhibition of the CDK5/Nrf2/GPX4 pathway. (Apoptosis : an international journal on programmed cell death, 2026, PMID 42178429): "This study aimed to determine the effect of Artesunate (ART) on oxaliplatin-resistance of colorectal cancer (CRC) and the underlying mechanism."
• May Pharmacokinetic and pharmacogenomic profile of capecitabine and oxaliplatin in a patient with gastric cancer undergoing hemodialysis: a case report. (Cancer chemotherapy and pharmacology, 2026, PMID 42126571): "This study aimed to evaluate the efficacy and safety of the capecitabine plus oxaliplatin (CapeOX) regimen in a 73-year-old male Japanese patient with stage IV gastric cancer (human epidermal growth factor receptor 2 negative) undergoing hemodialysis."
• May Postoperative Hepatic Arterial Infusion With Oxaliplatin After Surgery of Four or More Colorectal Liver Metastases: A Randomized Phase II Trial. (Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2026, PMID 42018958): "To evaluate the efficacy and safety of adjuvant hepatic arterial infusion (HAI) of oxaliplatin combined with intravenous (IV) fluorouracil/leucovorin (LV5FU2) after curative-intent surgery of ≥4 colorectal liver metastases (CRLM)."
• Apr Docetaxel-Induced Immune Activation Shows Antitumor Synergy With the Tumor-Targeted CD40 Agonist KK2269. (Cancer science, 2026, PMID 41989931): "KK2269 showed significant antitumor activity in combination with an anti-PD-1 antibody, docetaxel, doxorubicin, or oxaliplatin, but not gemcitabine, with docetaxel showing the most significant antitumor effect(s)."
• Jun Synergistic induction of immunogenic cell death and tumor microenvironment remodeling by biotinylated marine polysaccharide nanoparticles for enhanced colorectal cancer therapy. (Carbohydrate polymers, 2026, PMID 41943296): "Although the combination of oxaliplatin (OXA, chemotherapy) and fruquintinib (FRU, antiangiogenic) shows clinical promise, their divergent physicochemical properties and inadequate tumor selectivity lead to suboptimal efficacy and systemic toxicity."