P2, N=130, Recruiting, Second Affiliated Hospital of Guangzhou Medical University | Not yet recruiting --> Recruiting

Thus, potential correlations were observed among ketogenesis, stemness, and iron homeostasis. This finding can be used to formulate a new strategy for overcoming oxaliplatin resistance in patients with CRC.

Research on the relationship between HIF-1α levels and the clinical effect of oxaliplatin is lacking, and whether liensinine regulates HIF-1α is unknown. Our findings suggest that liensinine overcomes the resistance of colorectal cancer cells to oxaliplatin by suppressing HIF-1α levels to inhibit autophagy. Our findings can contribute to improving prognosis following colorectal cancer therapy.

The inhibitory influence of 3-MA on HMGB1 reversed the influence of Gfi-1 on autophagy and malignant progression in CRC cells. Our study suggested that Gfi-1 inhibited HMGB1 to reduce CRC autophagy levels, increasing CRC sensitivity to L-OHP.

P2, N=130, Not yet recruiting, Second Affiliated Hospital of Guangzhou Medical University

The findings indicate a potential role of 5 mg/mL APS in modulating the PD-1/PD-L1 pathway and influencing the immune response, encompassing T cells and macrophages. Consequently, further in vivo research is recommended to assess the efficacy of APS.

Moreover, the detoxification mechanism of oxaliplatin, which represents the first line of treatment for advanced CRC, is mediated via certain GSTs... Both GSTM1-null and GSTP1 IleVal+ValVal (variant) genotypes are associated with significantly shorter survival in CRC patients. What is more, the GSTM1-null genotype is associated with shorter survival in patients receiving FOLOFOX6 treatment.

Recently, hope has been raised regarding the catalytic antioxidants mangafodipir (MnDPDP) and calmangafodipir [Ca4Mn(DPDP)5; PledOx®], which by mimicking mitochondrial manganese superoxide dismutase (MnSOD) may be expected to overcome oxaliplatin-associated chemotherapy-induced peripheral neuropathy (CIPN)...However, pharmacokinetic considerations suggest that the efficacy of MnDPDP on Pt2+-associated neurotoxicity depends on another action of this drug. Electron paramagnetic resonance (EPR) studies have demonstrated that Pt2+ outcompetes Mn2+ and endogenous Zn2+ in binding to fodipir (DPDP), hence suggesting that the previously reported protective efficacy of MnDPDP against CIPN is a result of chelation and elimination of Pt2+ by DPDP, which in turn suggests that Mn2+ is unnecessary for efficacy when it comes to oxaliplatin-associated CIPN.

Flow cytometry analysis revealed increased infiltration of activated cytotoxic (CD8⁺, PD-1⁺) T-cells and anti-tumor cytokines (IFNγ and Granzyme B) in the tumor tissues of the combination therapy group, suggesting that this may be the primary mechanism behind the anti-tumor effect of the combination treatment. These findings indicate that MC-LR regulates the immune stimulation of macrophage polarization and dendritic cell maturation, effectively reversing tumor immunosuppression, activating an anti-tumor immune response, and enhancing tumor therapy.

The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184. This regulatory mechanism enhances CRC progression and resistance to oxaliplatin, positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

Here, we revealed the contribution of F. nucleatum to oxaliplatin resistance by inhibiting ferroptosis in CRC. Targeting F. nucleatum and ferroptosis will provide valuable insight into chemoresistance management and may improve outcomes for patients with CRC.

We presented a case of locally advanced ascending colon cancer in a 17-year-old female patient. CRC rarely occurs in AYAs. However, the incidence has gradually increased in recent years. It should be considered as a differential diagnosis for young patients with long-term abdominal symptoms of unknown cause.

In addition, high-risk patients showed better sensitivity to Erlotinib, Oxaliplatin, and Gefitinib. Furthermore, three novel molecular subtypes of STAD were identified based on the 2-DRLs features, with evaluation of the immune microenvironment and chemotherapy drug sensitivity for each subgroup, which holds significant implications for achieving precise treatment in STAD. Overall, our 2-DRLs prognostic model demonstrates high predictive value for patient survival in STAD, potentially providing new targets for individualized immune and chemical therapy.

P4, N=642, Not yet recruiting, Health Science Center of Xi'an Jiaotong University

In addition to its excellent antitumor activity, Oxa@Mil-100(Fe) has no obvious toxic or side effects. This study provides a new idea and method for the combined treatment of gastric cancer.

The aim of the study was to assess the efficacy and toxicity of fludarabine, cytarabine, and granulocyte-colony stimulation factor (FLAG) with or without idarubicin (-Ida) and to discuss novel therapies in this setting. Among the variables, including age, FLT3 mutation status, European LeukemiaNet (ELN) 2022 classification risk, FLAG vs. FLAG-Ida, and aHSCT, a multivariate analysis revealed that only aHSCT significantly influenced overall survival. (4) FLAG(-Ida) chemotherapy remains an effective salvage chemotherapy for patients with r/r and secondary AML with a plan of proceeding to aHSCT.

P2, N=54, Not yet recruiting, Swiss Group for Clinical Cancer Research

This study found that 26.0% of patients with oxaliplatin-induced ADRs could not undergo oxaliplatin rechallenge. HLA-DRB∗12:01 is regarded as a genetic marker for oxaliplatin-induced hypersensitivity.

We constructed a TGCP model, which demonstrates satisfactory predictive accuracy. Out of 9 prognostic genes, TAP1 was validated as a synergistic target for Oxaliplatin and PDL1 inhibitors, offering a genetic-level explanation for the synergy observed in GC treatment involving Oxaliplatin in combination with PDL1 inhibitors.

"BACKGROUND: Systemic therapies such as fruquintinib, regorafenib, and trifluridine/tipiracil (T/T) have demon- strated survival benefits vs best supportive care (BSC) in patients with metastatic colorectal cancer (mCRC) pre- viously treated with oxaliplatin- and irinotecan-based chemotherapy (OIC)...OBJECTIVE: To compare the AE management costs of fruquin- tinib, regorafenib, T/T and T/T+bevacizumab (T/T+bev) for mCRC previously treated with OIC, from US Commercial and Medicare payer perspectives... Based on the cost-consequence model results, fruquintinib was associated with lower AE manage- ment costs compared with regorafenib, T/T, and T/T+bev for patients with mCRC previously treated with OIC, which should be considered in treatment and formulary decision- making."

SMAD3 inhibition diminished ATM phosphorylation by enhancing the binding of PP2A to ATM, causing excessive levels of DNA damage. Our results identify SMAD3 as a promising therapeutic target for future combination strategies for the treatment of patients with EAC.

P=N/A, N=230, Recruiting, Jules Bordet Institute | Not yet recruiting --> Recruiting

Although 3 µM dasatinib reduced 100 µM OHP accumulation in hOCT2-HEK293 cells, co-incubation with dasatinib and OHP did not prevent OHP toxicity, possibly due to dasatinib-induced cell viability reduction. In summary, this study demonstrates OHP as an OCT2 substrate and dasatinib as a non-transported inhibitor and regulator of OCT2, offering potential for OIPN mitigation.

A 44-year-old woman was diagnosed with acute myeloid leukemia (RUNX1::RUNX1T1 translocation) and received induction chemotherapy with idarubicin hydrochloride and cytosine arabinoside. The patient received consolidation chemotherapy, and has maintained complete remission. Severe respiratory failure during induction chemotherapy for acute leukemia can be fatal, but VV-ECMO may be lifesaving.

P=N/A, N=63, Active, not recruiting, Washington University School of Medicine | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2024 --> Sep 2024

Our integrative approach, amalgamating mIHC assays, feature extraction, and machine learning, successfully unraveled the complex cellular interplay underlying drug resistance. This robust predictive model may serve as a valuable tool for personalizing therapeutic strategies and enhancing treatment outcomes in gastric cancer.

It further verified the results of our in vitro and in vivo experiments, showing the involvement of multi-component, multi-target, and multi-pathway synergism in the drug-reversing effect of LBP in CC. Overall, the findings of the present study provide new avenues for the future clinical treatment of CC.

P=N/A, N=20, Recruiting, Wake Forest University Health Sciences | Trial primary completion date: Mar 2024 --> Jun 2024

P3, N=545, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: May 2024 --> Aug 2024

In vivo experiments further validated the influence of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells through PTEN regulation. In conclusion, SNHG4 promotes resistance to oxaliplatin in CRC cells by suppressing ferroptosis through instability of PTEN, thus serves as a target for patients with oxaliplatin-base chemoresistance.

In this study, we designed a novel Pt(IV) complex, OAP2, which is composed of oxaliplatin (Oxa) and acetaminophen (APAP), to enhance its anti-tumor effects and amplify the immune response...OAP2 also promotes dendritic cell maturation and enhances the quantity and efficacy of cytotoxic T cells, thereby inhibiting cancer cell proliferation and metastasis. Briefly, our study introduces the first novel small-molecule inhibitor that regulates mitochondrial membrane remodeling for active immunotherapy in anti-tumor research, which may provide a creative idea for targeting organelle in anti-tumor therapy.

We found that 200 mg/m2 oxaliplatin administered for 120 min is the most effective HIPEC treatment option within the framework of clinic applications. The tool map provide insights into creating more realistic pre-clinical tools that could be used for a patient-based drug screening.

Experimental evidence further demonstrates that SPINK1 overexpression induces the expression of CES2 and CYP3A5, consequently promoting chemoresistance to sorafenib and oxaliplatin. In summary, our study unveils the predictive role of SPINK1 on HCC treatment resistance, identifying it as a potential therapeutic target for refractory HCC.

The study findings will be submitted to peer-reviewed journals for publication. Chinese Clinical Trials Registry (ChiCTR2300075861).

Here, we showed an oral compound (Z526) exhibited potent alleviating effects on C2C12 myotube atrophy induced by various chemotherapeutic agents in vitro as well as mice muscle loss and impaired grip force induced by oxaliplatin in vivo...The pharmacological effects of Z526 were based on its potency in reducing oxidative stress in cachectic myocytes and muscle tissues, which inhibited the activation of NF-κB and STAT3 to decrease Atrogin-1-mediated protein degradation, activated the AKT/mTOR signaling pathway to promote protein synthesis, regulated Bcl-2/BAX ratio to reduce Caspase-3-triggered apoptosis. Our work suggested Z526 to be an optional strategy for ameliorating cachexia muscle atrophy in the multimodality treatment of cancers.

Their inhibition activities against different types of cancer were screened and some derivatives showed superior anti-non-small cell lung cancer (NSCLC) cells cytotoxic potencies than oxaliplatin...Remarkably, 13-OD, B6, A2, and A10-2 induced mitophagy and ferroptosis. In summary, our results reveal that 13-OD, B6, A2, and A10-2 holds great potential in developing anti-tumor agents for targeting TMBIM6.

Murine and human PDAC cell lines were treated with small interfering RNA (siRNA) against sphingosine kinase-2 (SPHK2) or ABC294640 (ABC) and incubated with combinations of vehicle control or Oxa. Furthermore, S1P inhibition can sensitize PDAC to Oxa therapy through increasing ER stress and can potentiate ICD induction. This highlights a potential therapeutic target for chemosensitizing PDAC as well as an adjunct for future chemoimmunotherapy strategies.

P1, N=24, Recruiting, Arjun Mittra | Not yet recruiting --> Recruiting

P2, N=255, Active, not recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Recruiting --> Active, not recruiting | Trial completion date: Jun 2023 --> Jun 2025

In conclusion, the knockdown of S100A6 may overcome the L-OHP resistance of CRC cells by modulating EMT.

The depletion of APLF sensitizes cells to cisplatin and results in fork instability. Our results reveal the novel function of APLF to facilitate ICL repair and fork protection, thereby contributing to cisplatin-resistant phenotypes of cancer cells.

Besides, USP36 was further up-regulated in oxaliplatin (Oxa)-resistant colon cancer cells...Moreover, in vivo analyses confirmed the oncogenic role of USP36 and the therapeutic potential of CBF in the malignancy of colon cancer. In conclusion, CBF may be a promising therapeutic agent for colon cancer due to its regulation of the USP36/c-Myc axis.