Disease Information

General Information of the Disease (ID: DIS00108)

• Name: Pituitary cancer
• ICD: ICD-11: 2F37

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  RTDM: Regulation by the Disease Microenvironment

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 8 drug(s) in total

Bromocriptine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Dopamine receptor D2 (DRD2) [2]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Generally, the effectiveness of BRC or CAB has been related to a decreased expression in DRs, as the expression of such receptors has been shown to correlate with responsiveness to therapy in lactotroph, somatotroph, corticotroph and in clinically nonfunctioning PitNET.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-17-5p [3]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: C4-2 cells; Prostate; Homo sapiens (Human); CVCL_4782
• Experiment for Molecule Alteration: Solexa sequencing assay; qRT-PCR
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: Overexpression of mir-93 increased resistance to bromocriptine and cabergoline treatment.

Key Molecule: hsa-mir-126 [3]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: KHM-5M cells; Pleural effusion; Homo sapiens (Human); CVCL_2975
• Experiment for Molecule Alteration: Solexa sequencing assay; qRT-PCR
• Experiment for Drug Resistance: Clinical diagnostic evaluation
• Mechanism Description: Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.

Key Molecule: hsa-mir-136 [3]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: KHM-5M cells; Pleural effusion; Homo sapiens (Human); CVCL_2975
• Experiment for Molecule Alteration: Solexa sequencing assay; qRT-PCR
• Experiment for Drug Resistance: Clinical diagnostic evaluation
• Mechanism Description: Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.

Key Molecule: hsa-miR-142-3p [3]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: KHM-5M cells; Pleural effusion; Homo sapiens (Human); CVCL_2975
• Experiment for Molecule Alteration: Solexa sequencing assay; qRT-PCR
• Experiment for Drug Resistance: Clinical diagnostic evaluation
• Mechanism Description: Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.

Key Molecule: hsa-mir-144 [3]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: KHM-5M cells; Pleural effusion; Homo sapiens (Human); CVCL_2975
• Experiment for Molecule Alteration: Solexa sequencing assay; qRT-PCR
• Experiment for Drug Resistance: Clinical diagnostic evaluation
• Mechanism Description: Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.

Key Molecule: hsa-mir-17 [3]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: KHM-5M cells; Pleural effusion; Homo sapiens (Human); CVCL_2975
• Experiment for Molecule Alteration: Solexa sequencing assay; qRT-PCR
• Experiment for Drug Resistance: Clinical diagnostic evaluation
• Mechanism Description: Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.

Key Molecule: hsa-mir-22 [3]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: KHM-5M cells; Pleural effusion; Homo sapiens (Human); CVCL_2975
• Experiment for Molecule Alteration: Solexa sequencing assay; qRT-PCR
• Experiment for Drug Resistance: Clinical diagnostic evaluation
• Mechanism Description: Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.

Key Molecule: hsa-mir-30a [3]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: KHM-5M cells; Pleural effusion; Homo sapiens (Human); CVCL_2975
• Experiment for Molecule Alteration: Solexa sequencing assay; qRT-PCR
• Experiment for Drug Resistance: Clinical diagnostic evaluation
• Mechanism Description: Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.

Key Molecule: hsa-mir-382 [3]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: KHM-5M cells; Pleural effusion; Homo sapiens (Human); CVCL_2975
• Experiment for Molecule Alteration: Solexa sequencing assay; qRT-PCR
• Experiment for Drug Resistance: Clinical diagnostic evaluation
• Mechanism Description: Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.

Key Molecule: hsa-mir-451 [3]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: KHM-5M cells; Pleural effusion; Homo sapiens (Human); CVCL_2975
• Experiment for Molecule Alteration: Solexa sequencing assay; qRT-PCR
• Experiment for Drug Resistance: Clinical diagnostic evaluation
• Mechanism Description: Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.

Key Molecule: hsa-miR-486-5p [3]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: KHM-5M cells; Pleural effusion; Homo sapiens (Human); CVCL_2975
• Experiment for Molecule Alteration: Solexa sequencing assay; qRT-PCR
• Experiment for Drug Resistance: Clinical diagnostic evaluation
• Mechanism Description: Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.

Key Molecule: Long non-protein coding RNA (lnc886) [3]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: KHM-5M cells; Pleural effusion; Homo sapiens (Human); CVCL_2975
• Experiment for Molecule Alteration: Solexa sequencing assay; qRT-PCR
• Experiment for Drug Resistance: Clinical diagnostic evaluation
• Mechanism Description: Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.

Key Molecule: hsa-mir-93 [3]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: C4-2 cells; Prostate; Homo sapiens (Human); CVCL_4782
• In Vitro Model: KHM-5M cells; Pleural effusion; Homo sapiens (Human); CVCL_2975
• Experiment for Drug Resistance: Clinical diagnostic evaluation
• Mechanism Description: Hsa-mir-93, hsa-mir-17, hsa-mir-22*, hsa-mir-126*, hsa-mir-142-3p, hsa-mir-144*, hsa-mir-486-5p, hsa-mir-451, and hsa-mir-92a were up-regulated and hsa-mir-30a, hsa-mir-382, and hsa-mir-136 were down-regulated in bromocriptine-resistant prolactinomas in comparison with bromocriptine-sensitive prolactinomas.

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: Mothers against decapentaplegic homolog 3 (SMAD3) [4]

• Resistant Disease: Prolactinomas [ICD-11: 2F37.2]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: TGF-beta 1/Smad3 pathway; Activation; hsa04350
• In Vitro Model: HS27 cells; Bone; Homo sapiens (Human); CVCL_0E34
• In Vitro Model: MMQ cells; Pituitary gland; Rattus norvegicus (Rat); CVCL_2117
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: TGF-beta1 promotes the synthesis and secretion of collagen fibers in fibroblasts and that the TGF-beta1/Smad3 pathway is involved in the mechanism of prolactinoma resistance by increasing fibrosis through interactions with fibroblasts.

Key Molecule: Mothers against decapentaplegic homolog 4 (SMAD4) [4]

• Resistant Disease: Prolactinomas [ICD-11: 2F37.2]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: TGF-beta 1/Smad3 pathway; Activation; hsa04350
• In Vitro Model: HS27 cells; Bone; Homo sapiens (Human); CVCL_0E34
• In Vitro Model: MMQ cells; Pituitary gland; Rattus norvegicus (Rat); CVCL_2117
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: TGF-beta1 promotes the synthesis and secretion of collagen fibers in fibroblasts and that the TGF-beta1/Smad3 pathway is involved in the mechanism of prolactinoma resistance by increasing fibrosis through interactions with fibroblasts.

Key Molecule: TSPY like 2 (TSPYL2) [4]

• Resistant Disease: Prolactinomas [ICD-11: 2F37.2]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: TGF-beta 1/Smad3 pathway; Activation; hsa04350
• In Vitro Model: HS27 cells; Bone; Homo sapiens (Human); CVCL_0E34
• In Vitro Model: MMQ cells; Pituitary gland; Rattus norvegicus (Rat); CVCL_2117
• Experiment for Molecule Alteration: Western blotting assay
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: TGF-beta1 promotes the synthesis and secretion of collagen fibers in fibroblasts and that the TGF-beta1/Smad3 pathway is involved in the mechanism of prolactinoma resistance by increasing fibrosis through interactions with fibroblasts.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cyclin-dependent kinase inhibitor 1A (CDKN1A) [3]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• In Vitro Model: C4-2 cells; Prostate; Homo sapiens (Human); CVCL_4782
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: Knockdown of mir-93 increased the sensitivity of MMQ cells to bromocriptine treatment, and these effects were abolished when p21 was knocked-down using siRNA.

Key Molecule: Androgen receptor (AR) [5]

• Resistant Disease: Prolactinomas [ICD-11: 2F37.2]
• Resistant Drug: Bromocriptine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: GH3 cells; Pituitary gland; Rattus norvegicus (Rat); CVCL_0273
• In Vitro Model: MMQ cells; Pituitary gland; Rattus norvegicus (Rat); CVCL_2117
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: AR plays a crucial role in mediating DA resistance in PRL adenoma. Mechanistically, AR promotes cell proliferation and PRL secretion and confers drug resistance by transcriptionally regulating NRF2 expression to maintain redox homeostasis in PA cells. Finally, combining AR targeting agents with BRC shows promise as a therapeutic strategy for treating PRL adenomas.?Antioxid. Redox Signal.

Cabergoline

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Dopamine receptor D2 (DRD2) [2]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Cabergoline
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Generally, the effectiveness of BRC or CAB has been related to a decreased expression in DRs, as the expression of such receptors has been shown to correlate with responsiveness to therapy in lactotroph, somatotroph, corticotroph and in clinically nonfunctioning PitNET.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-17-5p [3]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Cabergoline
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: C4-2 cells; Prostate; Homo sapiens (Human); CVCL_4782
• Experiment for Molecule Alteration: Solexa sequencing assay; qRT-PCR
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: Overexpression of mir-93 increased resistance to bromocriptine and cabergoline treatment.

Key Molecule: hsa-mir-93 [3]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Cabergoline
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: C4-2 cells; Prostate; Homo sapiens (Human); CVCL_4782
• Experiment for Molecule Alteration: Solexa sequencing assay; qRT-PCR
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: Overexpression of mir-93 increased resistance to bromocriptine and cabergoline treatment.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cyclin-dependent kinase inhibitor 1A (CDKN1A) [3]

• Resistant Disease: Prolactin-secreting adenoma [ICD-11: 2F37.Y]
• Resistant Drug: Cabergoline
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: C4-2 cells; Prostate; Homo sapiens (Human); CVCL_4782
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: Knockdown of mir-93 increased the sensitivity of MMQ cells to bromocriptine treatment, and these effects were abolished when p21 was knocked-down using siRNA.

Carboplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Bcl-2-associated agonist of cell death (BAD) [6]

• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Resistant Drug: Carboplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pituitary tumour stem-like cells; Pituitary; Homo sapiens (Human); N.A.
• In Vivo Model: NOD/SCID mice xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: WST-1 proliferation assay
• Mechanism Description: Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.

Key Molecule: Baculoviral IAP repeat containing 2 (BIRC2) [6]

• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Resistant Drug: Carboplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pituitary tumour stem-like cells; Pituitary; Homo sapiens (Human); N.A.
• In Vivo Model: NOD/SCID mice xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: WST-1 proliferation assay
• Mechanism Description: Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.

Key Molecule: Baculoviral IAP repeat-containing protein 1 (BIRC1) [6]

• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Resistant Drug: Carboplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pituitary tumour stem-like cells; Pituitary; Homo sapiens (Human); N.A.
• In Vivo Model: NOD/SCID mice xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: WST-1 proliferation assay
• Mechanism Description: Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.

Key Molecule: E3 ubiquitin-protein ligase XIAP (XIAP) [6]

• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Resistant Drug: Carboplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pituitary tumour stem-like cells; Pituitary; Homo sapiens (Human); N.A.
• In Vivo Model: NOD/SCID mice xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: WST-1 proliferation assay
• Mechanism Description: Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.

Colchicine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [7]

• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Resistant Drug: Colchicine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: GH4C1 cells; Pituitary gland; Rattus norvegicus (Rat); CVCL_0276
• Experiment for Molecule Alteration: Immunocytochemical staining assay
• Experiment for Drug Resistance: Lowry assay; Bradford assay
• Mechanism Description: Cells resistant to colchicine at 0.4 micrograms/ml, termed GH4C1/RC.4, exhibited the multidrug-resistance phenotype, as the LD50 values for colchicine, puromycin, actinomycin D, and doxorubicin were between 8 and 30 times greater than the corresponding values for the parental GH4C1 cells.Immunocytochemical staining with a monoclonal antibody, C219, to the 170-kilodalton P-glycoprotein showed directly that GH4C1/RC.4 cells overexpress P-glycoprotein.

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [7]

• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: GH4C1 cells; Pituitary gland; Rattus norvegicus (Rat); CVCL_0276
• Experiment for Molecule Alteration: Immunocytochemical staining assay
• Experiment for Drug Resistance: Lowry assay; Bradford assay
• Mechanism Description: Cells resistant to colchicine at 0.4 micrograms/ml, termed GH4C1/RC.4, exhibited the multidrug-resistance phenotype, as the LD50 values for colchicine, puromycin, actinomycin D, and doxorubicin were between 8 and 30 times greater than the corresponding values for the parental GH4C1 cells.Immunocytochemical staining with a monoclonal antibody, C219, to the 170-kilodalton P-glycoprotein showed directly that GH4C1/RC.4 cells overexpress P-glycoprotein.

Etoposide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Bcl-2-associated agonist of cell death (BAD) [6]

• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Resistant Drug: Etoposide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pituitary tumour stem-like cells; Pituitary; Homo sapiens (Human); N.A.
• In Vivo Model: NOD/SCID mice xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: WST-1 proliferation assay
• Mechanism Description: Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.

Key Molecule: Baculoviral IAP repeat containing 2 (BIRC2) [6]

• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Resistant Drug: Etoposide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pituitary tumour stem-like cells; Pituitary; Homo sapiens (Human); N.A.
• In Vivo Model: NOD/SCID mice xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: WST-1 proliferation assay
• Mechanism Description: Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.

Key Molecule: Baculoviral IAP repeat-containing protein 1 (BIRC1) [6]

• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Resistant Drug: Etoposide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pituitary tumour stem-like cells; Pituitary; Homo sapiens (Human); N.A.
• In Vivo Model: NOD/SCID mice xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: WST-1 proliferation assay
• Mechanism Description: Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.

Key Molecule: E3 ubiquitin-protein ligase XIAP (XIAP) [6]

• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Resistant Drug: Etoposide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pituitary tumour stem-like cells; Pituitary; Homo sapiens (Human); N.A.
• In Vivo Model: NOD/SCID mice xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: WST-1 proliferation assay
• Mechanism Description: Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.

Octreotide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Forkhead box protein O3 (FOXO3) [8]

• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Resistant Drug: Octreotide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: HCT8 cells; Colon; Homo sapiens (Human); CVCL_2478
• In Vitro Model: LN-18 cells; Brain; Homo sapiens (Human); CVCL_0392
• In Vitro Model: ATCC 293T cells; Fetal kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: SH-1-V3 cells; Esophagus; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: WST-1 assay
• Mechanism Description: miR-34a upregulation leads not only to increased cell proliferation and GH secretion in vitro, but also induces resistance to the antiproliferative and hormonal effects of the first-generation somatostatin analog, octreotide.

Temozolomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: DNA mismatch repair protein Msh6 (MSH6) [9]

• Resistant Disease: Pituitary cancer [ICD-11: 2F37.0]
• Resistant Drug: Temozolomide
• Molecule Alteration: Structural variation; Copy number loss
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Low throughput experiment assay
• Mechanism Description: Loss of MSH6 occurred during the progression from an atypical prolactinoma to a pituitary carcinoma, which may have caused resistance to TMZ treatment.

Investigative Drug(s) 2 drug(s) in total

Actinomycin D

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [7]

• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Resistant Drug: Actinomycin D
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: GH4C1 cells; Pituitary gland; Rattus norvegicus (Rat); CVCL_0276
• Experiment for Molecule Alteration: Immunocytochemical staining assay
• Experiment for Drug Resistance: Lowry assay; Bradford assay
• Mechanism Description: Cells resistant to colchicine at 0.4 micrograms/ml, termed GH4C1/RC.4, exhibited the multidrug-resistance phenotype, as the LD50 values for colchicine, puromycin, actinomycin D, and doxorubicin were between 8 and 30 times greater than the corresponding values for the parental GH4C1 cells.Immunocytochemical staining with a monoclonal antibody, C219, to the 170-kilodalton P-glycoprotein showed directly that GH4C1/RC.4 cells overexpress P-glycoprotein.

Puromycin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [7]

• Resistant Disease: Pituitary adenoma [ICD-11: 2F37.1]
• Resistant Drug: Puromycin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: GH4C1 cells; Pituitary gland; Rattus norvegicus (Rat); CVCL_0276
• Experiment for Molecule Alteration: Immunocytochemical staining assay
• Experiment for Drug Resistance: Lowry assay; Bradford assay
• Mechanism Description: Cells resistant to colchicine at 0.4 micrograms/ml, termed GH4C1/RC.4, exhibited the multidrug-resistance phenotype, as the LD50 values for colchicine, puromycin, actinomycin D, and doxorubicin were between 8 and 30 times greater than the corresponding values for the parental GH4C1 cells.Immunocytochemical staining with a monoclonal antibody, C219, to the 170-kilodalton P-glycoprotein showed directly that GH4C1/RC.4 cells overexpress P-glycoprotein.

References

• Ref 1: TRIM21-mediated ubiquitination and phosphorylation of ERK1/2 promotes cell proliferation and drug resistance in pituitary adenomas. Neuro Oncol. 2025 Mar 7;27(3):727-742.
• Ref 2: Resistance to Dopamine Agonists in Pituitary Tumors: Molecular Mechanisms .Front Endocrinol (Lausanne). 2022 Jan 12;12:791633. doi: 10.3389/fendo.2021.791633. eCollection 2021. 10.3389/fendo.2021.791633
• Ref 3: MicroRNA expression profile of bromocriptine-resistant prolactinomas .Mol Cell Endocrinol. 2014 Sep;395(1-2):10-8. doi: 10.1016/j.mce.2014.07.014. Epub 2014 Jul 23. 10.1016/j.mce.2014.07.014
• Ref 4: Role of TGF-Beta1/Smad3-mediated fibrosis in drug resistance mechanism of prolactinoma .Brain Res. 2018 Nov 1;1698:204-212. doi: 10.1016/j.brainres.2018.07.024. Epub 2018 Jul 27. 10.1016/j.brainres.2018.07.024
• Ref 5: Androgen Receptor Mediates Dopamine Agonist Resistance by Regulating Intracellular Reactive Oxygen Species in Prolactin-Secreting Pituitary Adenoma. Antioxid Redox Signal. 2025 Jun;42(16-18):954-972.
• Ref 6: Isolation of tumour stem-like cells from benign tumours .Br J Cancer. 2009 Jul 21;101(2):303-11. doi: 10.1038/sj.bjc.6605142. Epub 2009 Jun 30. 10.1038/sj.bjc.6605142
• Ref 7: Characterization of multidrug-resistant pituitary tumor cells .Endocrinology. 1992 Jun;130(6):3246-56. doi: 10.1210/endo.130.6.1350759. 10.1210/endo.130.6.1350759
• Ref 8: miR-34a is upregulated in AIP-mutated somatotropinomas and promotes octreotide resistance .Int J Cancer. 2020 Dec 15;147(12):3523-3538. doi: 10.1002/ijc.33268. Epub 2020 Sep 10. 10.1002/ijc.33268
• Ref 9: A mechanism of acquiring temozolomide resistance during transformation of atypical prolactinoma into prolactin-producing pituitary carcinoma: case report. Neurosurgery. 2011 Jun;68(6):E1761-7; discussion E1767. doi: 10.1227/NEU.0b013e318217161a.