Drug Information

Drug (ID: DG02042) and It's Reported Resistant Information

• Name: PD-1 mAb
• Indication:
  In total 1 Indication(s)
  . .; .
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Liver cancer [ICD-11: 2C12]; [1]

Type(s) of Resistant Mechanism of This Drug

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Liver cancer [ICD-11: 2C12]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Histone H3 [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Molecule Alteration: Lactylation; H3K18la
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Control into wild-type C57B/6 mice; Mice
• Experiment for Molecule Alteration: Western blot analysis
• Mechanism Description: SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8 T cell activity.

Key Molecule: Histone H3 [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Molecule Alteration: Lactylation; H3K18la
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Immunocompetent mice inoculated with control Hepa1-6 cells; Mice
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8 T cell activity.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Histone H3 [1]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Molecule Alteration: Lactylation; H3K18la
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: ShSrsf10 Hepa1-6 cells into wild-type C57B/6 mice; Mice
• Experiment for Molecule Alteration: Western blot analysis
• Mechanism Description: SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8 T cell activity.

Key Molecule: Histone H3 [1]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.02]
• Molecule Alteration: Lactylation; H3K18la
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Immunocompetent mice inoculated with shSrsf10 cells; Mice
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: SRSF10 was upregulated in various tumors and associated with poor prognosis. Moreover, SRSF10 positively regulated lactate production, and SRSF10/glycolysis/ histone H3 lysine 18 lactylation (H3K18la) formed a positive feedback loop in tumor cells. Increased lactate levels promoted M2 macrophage polarization, thereby inhibiting CD8 T cell activity.

References

• Ref 1: Targeting SRSF10 might inhibit M2 macrophage polarization and potentiate anti-PD-1 therapy in hepatocellular carcinoma. Cancer Commun (Lond). 2024 Nov;44(11):1231-1260.