Drug Information

Drug (ID: DG02005) and It's Reported Resistant Information

• Name: V9302
• Indication:
  In total 1 Indication(s)
  . .; .
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Pancreatic cancer [ICD-11: 2C10]; [1]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Pancreatic cancer [ICD-11: 2C10]; [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

Pancreatic cancer [ICD-11: 2C10]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Monocarboxylate transporter 1 (MCT1) [1]

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: PDAC patients; Homo Sapiens
• Experiment for Molecule Alteration: qPCR
• Mechanism Description: Metabolic pressures like glutamine deficiency lead to the emergence of an aggressive and poor prognostic reverse Warburg phenotype in PDAC. As the major fuel of this phenotype, lactate taken up by MCT1 maintains cellular redox homeostasis and thereby cell viability during critical shortages of glutamine supply. This also manifests in resistance against inhibitors of glutamine metabolism, thus limiting their usage in the clinic.

Key Molecule: Monocarboxylate transporter 1 (MCT1) [1]

• Metabolic Type: Glutamine metabolism
• Resistant Disease: Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A818-6 cells; Pancreas; Homo sapiens (Human); CVCL_3893
• In Vitro Model: T3M4 cells; Pancreas; Homo sapiens (Human); CVCL_4056
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: Metabolic pressures like glutamine deficiency lead to the emergence of an aggressive and poor prognostic reverse Warburg phenotype in PDAC. As the major fuel of this phenotype, lactate taken up by MCT1 maintains cellular redox homeostasis and thereby cell viability during critical shortages of glutamine supply. This also manifests in resistance against inhibitors of glutamine metabolism, thus limiting their usage in the clinic.

References

• Ref 1: Monocarboxylate Transporter-1 (MCT1)-Mediated Lactate Uptake Protects Pancreatic Adenocarcinoma Cells from Oxidative Stress during Glutamine Scarcity Thereby Promoting Resistance against Inhibitors of Glutamine Metabolism. Antioxidants (Basel). 2023 Sep 30;12(10):1818.