P2, N=46, Completed, Yale University | Active, not recruiting --> Completed

P=N/A, N=40, Suspended, NYU Langone Health | Trial completion date: Jun 2026 --> Jun 2027 | Recruiting --> Suspended | Trial primary completion date: Apr 2026 --> Apr 2027

Herein, we present a case of advanced MSS gastric cancer with liver and bulky lymph node metastases, in which combination therapy with S-1 plus oxaliplatin (SOX) and nivolumab led to a pathological complete response...This case illustrates that even in MSS gastric cancer with low TMB levels, exceptionally high PD-L1 expression may predict a profound response to ICI-based therapy. The PD-L1 CPS may serve as a critical biomarker independent of TMB or microsatellite-instability status.

These findings highlight the utility of expanded analysis of routinely obtained NGS panel results at the time of CRC diagnosis at many medical centers to personalize the chemotherapy regimen. Our data suggest that patients who carry the ERCC1 rs11615 (A>G) variant may be protected from developing oxaliplatin-induced SOS and those lacking the G allele should be monitored more carefully after oxaliplatin use.

Treatment with the SERCA agonist CDN1163 (CDN), the ethyl acetate extract of SKM (SKM.Ext), or duloxetine (DLX) attenuated neuronal pathology, restored DRG neuron soma diameter, and reduced the expression of pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α). Collectively, these findings demonstrate that activation of SERCA2b by CDN1163 or Schefflera kwangsiensis extract enhances SERCA2b expression, reduces DRG neuronal sensitization, and alleviates OIPN. This work supports SERCA2b as a novel therapeutic target for OXA-induced neuropathy and expands the potential clinical analgesic indications of Schefflera kwangsiensis.

The inhibition of the downstream transcription factor of ER stress ATF4 activation leads to the suppression of the anti-ferroptosis gene NRF2 transcription, thereby promoting ferroptosis in HCC cells and enhancing their sensitivity to oxaliplatin. In summary, SIRT3 enhances the sensitivity of HCC cells to oxaliplatin by promoting ferroptosis through the inhibition of GRP78-mediated ERS and regulation of the ATF4/NRF2 axis.

Activation of SOX9 through the APE1-redox function is a key driver of EAC chemoresistance. Targeting APE1's redox activity offers a promising therapeutic strategy to overcome resistance by inhibiting the otherwise "undruggable" SOX9 transcription network.

P1/2, N=13, Not yet recruiting, UZ Leuven

P2, N=236, Not yet recruiting, Sixth Affiliated Hospital, Sun Yat-sen University | Trial completion date: Nov 2030 --> Mar 2031 | Initiation date: Nov 2025 --> Mar 2026 | Trial primary completion date: Nov 2027 --> Mar 2031

Oxaliplatin-triggered chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cancer treatment that limits the efficacy of chemotherapy and negatively impacts patients' quality of life dramatically. Notably, inhibition of TXNIP with verapamil reduced oxidative stress levels. Our results demonstrated the use of DRG explants as an efficient model to study the mechanisms of CIPN and screen for potential treatments.

This study evaluated the association between baseline ctDNA levels and changes in ctDNA during treatment with response and survival outcomes in the phase II ALTER-C-002 trial, which investigated first-line anlotinib combined with capecitabine and oxaliplatin in patients with rat sarcoma (RAS) and B-Raf proto-oncogene (BRAF) wild-type metastatic colorectal cancer. Furthermore, KRAS/BRAF mutations detected in ctDNA were linked to shorter PFS and OS (all p<0.05). In conclusion, baseline ctDNA burden and early ctDNA clearance may function as prognostic and on-treatment biomarkers of therapeutic efficacy in metastatic colorectal cancer, warranting prospective validation.

P=N/A, N=90, Recruiting, University Hospital, Clermont-Ferrand