Drug Information

Drug (ID: DG00474) and It's Reported Resistant Information

• Name: Rituximab/Doxorubicin
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  COVID-19 [ICD-11: 1D92]; [1]

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Diffuse large B-cell lymphoma [ICD-11: 2A81]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Naaladl2-as2 [2]

• Sensitive Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK 293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: U-2932 cells; Blood; Homo sapiens (Human); CVCL_1896
• In Vitro Model: OCI-LY19 cells; Bone marrow; Homo sapiens (Human); CVCL_1878
• In Vivo Model: Athymic BALB/c nude mice model; Mus musculus
• Experiment for Molecule Alteration: Fluorescence in situ hybridization assay; Small interfering RNA assay; Luciferase reporter assay; Fluorescent qPCR; Western blot assay
• Experiment for Drug Resistance: MTT assay; Drug sensitivity testing
• Mechanism Description: We observed elevated levels of NAALADL2-AS2 in DLBCL tissues. We discovered that NAALADL2-AS2 functions as ceRNA to inhibit expression of miR-34a, miR-125a, whereas overexpression of NAALADL2-AS2 indirectly upregulates expression of BCL-2. Interfering with NAALADL2-AS2 promoted apoptosis in DLBCL cells, resulting in approximately a 40% increase in sensitivity to doxorubicin and rituximab. In vivo experiments further confirmed that targeting NAALADL2-AS2 effectively suppressed tumor growth, leading to upregulation of miR-34a and miR-125a, downregulation of BCL-2, and enhanced apoptosis in DLBCL cells, which significantly improved their sensitivity to doxorubicin and rituximab by approximately 50%.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-370-3p [3]

• Sensitive Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MAPK/BCR/PI signaling pathway; Regulation; N.A.
• In Vitro Model: SUDHL-4 cells; Peritoneal effusion; Homo sapiens (Human); CVCL_0539
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CellTiter-Blue Cell Viability assay
• Mechanism Description: miR370-3p, miR381-3p, and miR409-3p miRNAs appear to be the most potent regulators of the MAPk, BCR, and PI signaling system. Overexpression of miR370-3p, miR381-3p, and miR409-3p increases sensitivity to rituximab and doxorubicin.

Key Molecule: hsa-miR-381-3p [3]

• Sensitive Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MAPK/BCR/PI signaling pathway; Regulation; N.A.
• In Vitro Model: SUDHL-4 cells; Peritoneal effusion; Homo sapiens (Human); CVCL_0539
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CellTiter-Blue Cell Viability assay
• Mechanism Description: miR370-3p, miR381-3p, and miR409-3p miRNAs appear to be the most potent regulators of the MAPk, BCR, and PI signaling system. Overexpression of miR370-3p, miR381-3p, and miR409-3p increases sensitivity to rituximab and doxorubicin.

Key Molecule: hsa-miR-409-3p [3]

• Sensitive Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MAPK/BCR/PI signaling pathway; Regulation; N.A.
• In Vitro Model: SUDHL-4 cells; Peritoneal effusion; Homo sapiens (Human); CVCL_0539
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CellTiter-Blue Cell Viability assay
• Mechanism Description: miR370-3p, miR381-3p, and miR409-3p miRNAs appear to be the most potent regulators of the MAPk, BCR, and PI signaling system. Overexpression of miR370-3p, miR381-3p, and miR409-3p increases sensitivity to rituximab and doxorubicin.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Mitogen-activated protein kinase 1 (MAPK1) [3]

• Sensitive Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MAPK/BCR/PI signaling pathway; Regulation; N.A.
• In Vitro Model: SUDHL-4 cells; Peritoneal effusion; Homo sapiens (Human); CVCL_0539
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: CellTiter-Blue Cell Viability assay
• Mechanism Description: miR370-3p, miR381-3p, and miR409-3p miRNAs appear to be the most potent regulators of the MAPk, BCR, and PI signaling system. Overexpression of miR370-3p, miR381-3p, and miR409-3p increases sensitivity to rituximab and doxorubicin.

Key Molecule: PI3-kinase gamma (PIK3CG) [3]

• Sensitive Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: MAPK/BCR/PI signaling pathway; Regulation; N.A.
• In Vitro Model: SUDHL-4 cells; Peritoneal effusion; Homo sapiens (Human); CVCL_0539
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: CellTiter-Blue Cell Viability assay
• Mechanism Description: miR370-3p, miR381-3p, and miR409-3p miRNAs appear to be the most potent regulators of the MAPk, BCR, and PI signaling system. Overexpression of miR370-3p, miR381-3p, and miR409-3p increases sensitivity to rituximab and doxorubicin.

References

• Ref 1: Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies Nat Med. 2021 Apr;27(4):717-726. doi: 10.1038/s41591-021-01294-w. Epub 2021 Mar 4.
• Ref 2: NAALADL2-AS2 functions as a competing endogenous RNA to regulate apoptosis and drug resistance in DLBCL. Cancer Biol Ther. 2024 Dec 31;25(1):2432690.
• Ref 3: MicroRNAs regulate key cell survival pathways and mediate chemosensitivity during progression of diffuse large B-cell lymphoma. Blood Cancer J. 2017 Dec 15;7(12):654. doi: 10.1038/s41408-017-0033-8.