These findings indicate that TG4 is associated with chemotherapy-related reproductive toxicity and may represent a stress-responsive indicator of testicular injury. Further studies are required to determine whether TG4 plays a protective or pathogenic role in oxaliplatin-induced testicular damage and to evaluate its potential relevance in preserving fertility during platinum-based chemotherapy.

P2, N=50, Recruiting, National Cancer Centre, Singapore | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

We also observed a modulation of endoplasmic reticulum stress response, in particular decreased levels of ATF6, in LCS-knockdown cells treated with oxaliplatin. The present findings support the functional role of LCS in regulating the chemosensitivity of colon cancer cells towards the action of chemotherapy drugs, such as oxaliplatin, with possible further implications for the mechanisms underlying toxic action of platinum-based drugs in cancer cells.

We analyze resistance across major therapeutic modalities, including chemotherapeutics (5-fluorouracil, oxaliplatin, irinotecan), targeted agents (epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) inhibitors), and immune checkpoint inhibitors, with mechanistic insights directly linked to actionable, mechanism-guided interventions-including novel targeted agents, rational combination strategies, nanomedicine-based delivery systems, and emerging immunotherapeutic approaches. We further highlight convergent mechanisms that transcend individual therapies, particularly cancer stem cell plasticity and epigenetic reprogramming, which collectively drive multidrug resistance (MDR). Finally, in conjunction with emerging resistance detection technologies such as circulating tumor DNA (ctDNA), this review explores future directions for resistance monitoring and precision treatment adaptation, aiming to provide a systematic reference for overcoming therapeutic resistance in CRC.

The CCL3/CCR5 axis drives Oxa resistance in GC by boosting tumor cell survival and fostering immunosuppressive M2 macrophages. Targeting this pathway may offer a strategy to overcome chemoresistance in GC.

In this exploratory study of Japanese patients with colorectal cancer, SCN4A rs2302237 was consistently associated with a lower neuropathy-related symptom burden at both 0 M and 6 M. These findings suggest that SCN4A rs2302237 may be a candidate marker associated with patient-reported chronic OXAIPN symptom burden; however, larger validation studies are needed to confirm its clinical significance.

P=N/A, N=73, Completed, Nantes University Hospital | Active, not recruiting --> Completed | N=110 --> 73

This phase II study (ChiCTR2300077718) aimed to assess the efficacy and safety of balloon-occluded HAIC (bHAIC) based on the FOLFOX (oxaliplatin plus fluorouracil and leucovorin) regimen (bHAIC-FO) in unresectable HCC. bHAIC-FO demonstrates encouraging efficacy and acceptable safety profiles in unresectable HCC treatment, particularly in treatment-naive patients. www.chictr.org.cn, identifier ChiCTR2300077718.

In conclusion, SalB modulates CRC drug resistance through multiple targets and pathways. SalB potentially reverses oxaliplatin resistance in CRC cells by regulating the ROS-mediated apoptotic signalling pathway.

TPACD administration resulted in improvements in symptoms including fatigue, nausea, vomiting, loss of appetite, and oxaliplatin-induced peripheral neuropathy...TPACD serves as an effective, safe, well-tolerated, and readily acceptable complementary therapy for CRC patients undergoing CAPOX. https://www.chictr.org.cn/index.html, identifier ChiCTR2200065759.

Genetic depletion of TTI1 destabilizes ATM and ATR, attenuates DNA damage signaling, impairs double-strand break repair, and sensitizes colorectal cancer cells to 5-fluorouracil and oxaliplatin. These findings define a β-catenin-TTI1-ATM/ATR axis that links Wnt/β-catenin activation to DNA damage tolerance and chemotherapy response in colorectal cancer. Targeting TTI1 is therefore a promising approach to improve chemotherapy efficacy in Wnt/β-catenin-activated colorectal cancer.

LP treatment ameliorated these pathological alterations by restoring antioxidant enzyme activities, downregulating proinflammatory and proapoptotic signals, mitigating ER stress and autophagy activation, and reducing PI3K/AKT/mTOR protein expression. These findings demonstrate that LP exerts a renoprotective effect against OXI-induced kidney injury through multi-targeted molecular mechanisms, including modulation of inflammation, oxidative stress, autophagy, apoptosis, and survival signaling pathways.