Disease Information

General Information of the Disease (ID: DIS00565)

• Name: Unspecified carcinoma of unspecified site
• ICD: ICD-11: 2D41

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Idelalisib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Phosphatidylinositol 3-kinase delta short isoform (PI3Kdelta-S) [1]

• Resistant Disease: endocrine/solid tumors [ICD-11: 2D41]
• Resistant Drug: Idelalisib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: AKT/mTOR signaling pathway; Activation; hsa04150
• In Vitro Model: 22Rv-1 cells; Prostate; Homo sapiens (Human); CVCL_1045
• In Vitro Model: PC-3 cells; Bone; Homo sapiens (Human); CVCL_0035
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• In Vitro Model: MDA PCa 2b cells; Prostate; Homo sapiens (Human); CVCL_4748
• In Vitro Model: DU145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: MDA-MB-231cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MCF7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: SW620 cells; Colon; Homo sapiens (Human); CVCL_0547
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: NCI-H1299 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• Experiment for Molecule Alteration: Immunohistochemistry; Immunofluorescence staining assay; RT-PCR; Western blot assay
• Experiment for Drug Resistance: MTT assay; ELISA assay
• Mechanism Description: Overexpression of PIK3CD-S splice variant in PCa confers AA PCa resistance to PI3Kdelta inhibitor, such as Idelalisib. We also uncovered that the synthesis of aberrant PIK3CD-S splice variant is likely mediated by the splicing factor SRSF2, and inhibition of SRSF2 by SRPK1/2 inhibitor SRPIN340 significantly sensitizes AA PCa to Idelalisib.

References

• Ref 1: Aberrant PI3Kdelta splice isoform as a potential biomarker and novel therapeutic target for endocrine cancers. Front Endocrinol (Lausanne). 2023 Aug 21;14:1190479.