Chemoproteomics reveals berberine directly binds to PKM2 to inhibit the progression of colorectal cancer

Yan, Shihai; Hu, Li-Mu; Hao, Xue-Hui; Liu, Jiang; Tan, Xiying; Geng, Zhirong; Ma, Jing; Wang, Zhilin

doi:10.1016/j.isci.2022.104773

Cited by 15 publications

(12 citation statements)

References 53 publications

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“…The agreement between organoid and patient response to oxaliplatin-based treatment could result from removing of NAC from the screening medium and using the 5-FU:oxaliplatin ratio combination layout. A good association with patient response was found in a study that used a comparable ratio (14,20), while no association was found in studies that used different methods for combination screens(18, 21). Previous studies used DRC parameters AUC, IC 50 , and GR 50 to evaluate organoid response (12)(13)(14)21).…”

Section: Drc Metricsmentioning

confidence: 99%

“…This makes PDOs a novel promising biomarker to predict treatment response for various cancer and treatment types, and a valuable screening platform to identify new treatment types (9). Previous studies involving colorectal cancer (CRC) patients have demonstrated a correlation between organoid response and patient response to chemotherapy (9,(12)(13)(14)(15)(16)(17)(18)(19)(20). PDOs have, however, not consistently predicted the clinical outcome for oxaliplatin (18,21), resulting in considerable controversy surrounding the predictive value of PDOs for this standard mCRC treatment.…”

Section: Introductionmentioning

confidence: 99%

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Organoids as a biomarker for personalized treatment in metastatic colorectal cancer: drug screen optimization and correlation with patient response

Smabers,

Wensink,

Verissimo

et al. 2023

Preprint

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Background The inability to predict treatment response of colorectal cancer patients results in unnecessary toxicity, decreased efficacy and survival. Response testing on patient-derived organoids (PDOs) is a promising biomarker for treatment efficacy. The aim of this study is to optimize PDO drug screening methods for correlation with patient response and explore the potential to predict responses to standard chemotherapies.Methods We optimized drug screen methods on 5–11 PDOs per condition of the complete set of 23 PDOs from patients treated for metastatic colorectal cancer (mCRC). PDOs were exposed to 5-fluorouracil (5-FU), irinotecan- and oxaliplatin-based chemotherapy. We compared medium with and without N-acetylcysteine (NAC), different read-outs and different combination treatment layouts to capture the strongest association with patient response. We expanded the screens using the optimized methods for all PDOs. Organoid sensitivity was correlated to the patient’s response, determined by % change in the size of target lesions. We assessed organoid sensitivity in relation to prior exposure to chemotherapy, mutational status and sidedness.Results Drug screen optimization involved excluding N-acetylcysteine from the medium and biphasic curve fitting for 5-FU & oxaliplatin combination screens. CellTiter-Glo measurements were comparable with CyQUANT and did not affect the correlation with patient response. Furthermore, the correlation improved with application of growth rate metrics, when 5-FU & oxaliplatin was screened in a ratio, and 5-FU & SN-38 using a fixed dose of SN-38. Area under the curve was the most robust drug response curve metric. After optimization, organoid and patient response showed a correlation coefficient of 0.58 for 5-FU (n = 6, 95% CI -0,44-0.95), 0.61 for irinotecan- (n = 10, 95% CI − .03-0.90) and 0.60 for oxaliplatin-based chemotherapy (n = 11, 95% CI -0.01-0.88). Median progression-free survival of patients with resistant PDOs to oxaliplatin-based chemotherapy was significantly shorter than sensitive PDOs (3.3 vs 10.9 months, p = 0.007). Increased resistance to 5-FU in patients with prior exposure to 5-FU/capecitabine was adequately reflected in PDOs (p = 0.005).Conclusions Our study emphasizes the critical impact of the screening methods for determining correlation between PDO drug screens and mCRC patient outcomes. Our 5-step optimization strategy provides a basis for future research on the clinical utility of PDO screens.

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Section: Drc Metricsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Organoids as a biomarker for personalized treatment in metastatic colorectal cancer: drug screen optimization and correlation with patient response

Smabers,

Wensink,

Verissimo

et al. 2023

Preprint

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“…Berberine inhibited colorectal adenoma transformation to colorectal cancer by binding to pyruvate kinase isozyme type M2 (PKM2) and inhibiting the Warburg effect ( 137 ). Berberine-mediated inhibition of STAT3 decreased MMP2/9 expression to inhibit metastasis of established colorectal carcinomas ( 138 ).…”

Section: Berberinementioning

confidence: 99%

Natural biomolecules and derivatives as anticancer immunomodulatory agents

Bernitsa

Dayan²,

Stephanou³

et al. 2023

Front. Immunol.

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Despite advancements in chemotherapy, the issue of resistance and non-responsiveness to many chemotherapeutic drugs that are currently in clinical use still remains. Recently, cancer immunotherapy has gathered attention as a novel treatment against select cancers. Immunomodulation is also emerging as an effective strategy to improve efficacy. Natural phytochemicals, with known anticancer properties, been reported to mediate their effects by modulating both traditional cancer pathways and immunity. The mechanism of phytochemical mediated-immunomodulatory activity may be attributed to the remodeling of the tumor immunosuppressive microenvironment and the sensitization of the immune system. This allows for improved recognition and targeting of cancer cells by the immune system and synergy with chemotherapeutics. In this review, we will discuss several well-known plant-derived biomolecules and examine their potential as immunomodulators, and therefore, as novel immunotherapies for cancer treatment.

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“…These PTMs are mainly phosphorylation that is downregulated in CRC. However, several studies have shown that some plant-based dietary components such as phenols, flavonoids, terpenoids, and alkaloids could reverse it [ 123 , 126 , 128 , 135 , 137 , 139 , 140 , 146 , 147 ].…”

Section: Nutrigenomic Effects Of Plant-based Dietary Components On Pr...mentioning

confidence: 99%

Emerging Role of Plant-Based Dietary Components in Post-Translational Modifications Associated with Colorectal Cancer

Rodríguez-García

Gutiérrez-Santiago

2023

Life

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Colorectal cancer (CRC) is one of the most common cancers worldwide. Its main modifiable risk factors are diet, alcohol consumption, and smoking. Thus, the right approach through lifestyle changes may lead to its prevention. In fact, some natural dietary components have exhibited chemopreventive activity through modulation of cellular processes involved in CRC development. Although cancer is a multi-factorial process, the study of post-translational modifications (PTMs) of proteins associated with CRC has recently gained interest, as inappropriate modification is closely related to the activation of cell signalling pathways involved in carcinogenesis. Therefore, this review aimed to collect the main PTMs associated with CRC, analyse the relationship between different proteins that are susceptible to inappropriate PTMs, and review the available scientific literature on the role of plant-based dietary compounds in modulating CRC-associated PTMs. In summary, this review suggested that some plant-based dietary components such as phenols, flavonoids, lignans, terpenoids, and alkaloids may be able to correct the inappropriate PTMs associated with CRC and promote apoptosis in tumour cells.

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Chemoproteomics reveals berberine directly binds to PKM2 to inhibit the progression of colorectal cancer

Cited by 15 publications

References 53 publications

Organoids as a biomarker for personalized treatment in metastatic colorectal cancer: drug screen optimization and correlation with patient response

Organoids as a biomarker for personalized treatment in metastatic colorectal cancer: drug screen optimization and correlation with patient response

Natural biomolecules and derivatives as anticancer immunomodulatory agents

Emerging Role of Plant-Based Dietary Components in Post-Translational Modifications Associated with Colorectal Cancer

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