Table 11 Function of CDK4/6 in animal models of cancer

Acute myeloid leukemia

NOD/Shi-scid IL2Rgnull (NOG) mice

CDK4/6 inhibition: ↑ autophagy

Combination of CDK4/6 inhibition and autophagy inhibitor, chloroquine: ↓ tumor growth

[333]

4–6-week-old BALB/c nude mice

↑↑ miR-362-5p: ↑ tumor growth

[202]

Bladder cancer

mice

CDK4/6 inhibition and CDDP combination: ↓ tumor growth

[195]

6-week-old BALB/c-A nude mice

↑↑ miR-124: ↓ tumor growth

[203]

Breast cancer

6–7-week-old female FVB MMTV-PyMT, Balb/c (), and 8-week-old Foxn1nu mice

∆ CDK4/6: ↓ proliferation, ↑ anti-tumor immunity and cell cycle arrest

[198]

female nude mice

∆ PTEN: ↑ clinical cross-resistance to CDK4/6 and PI3Kα inhibitors via increased AKT activation

[172]

7-week-old female NOG CIEA mice

∆ CDK4/6 and AKT: ↓ tumor growth of ER + breast xenografts resistant to fulvestrant

[207]

6- to 8-week-old female NSG mice

6- to 8-week-old female immune-competent C57BL/6 mice

Combined PI3Kα and CDK4/6 inhibition: ↑ activation of tumor-infiltrating T-cell and cytotoxicity and ↓ immunosuppressive myeloid-derived suppressor cells

[208]

4-week-old BALB/c nude mice

Combined Inhibition of CDK2 and CDK4/6: ↓ resistance to Palbociclib

[98]

6-week-old female NOD-SCID mice

PARPi olaparib and the CDK4/6i palbociclib: ↓ tumor growth

[209]

6-week-old female BALB/c nude mice

∆ CDK4/6: ↓ tumor metastasis by destabilizing the ZEB1 protein

∆ USP51: ↓ tumor metastasis through the regulation of ZEB1

[210]

6-week-old CD-1 athymic nude mice

Blocking AKT/S6 signaling by targeting PI3K was found to be effective in blocking proliferation of palbociclib-resistant cells

[214]

6-week-old female athymic nude mice

CDK4/6 and PARP dual inhibitor, ZC-22: ↑ cell cycle arrest and ↑ DNA damage more than the combination of Olaparib and Abemaciclib, and ↑ response to Cisplatin

[217]

Female BALB nude mice

abemaciclib and ABT-263 combination: ↓ tumor growgh

[218]

4-week-old BALB/c nude mice

↑↑ miR-124: ↓ tumor growth

[219]

4-week-old nude mice

∆ MALAT1: ↑ inhibitory effect of miR-124 on the tumor growth

[222]

Cervical cancer

4–5-week-old male BALB/c nude mice

∆ circ_0000326: ↓ tumor growth

[227]

Clear cell renal cell carcinoma

4–5-week-old male BALB/c nude mice

↑↑ miR-1: ↓ tumor growth

[228]

NOD/SCID/IL2Rγ-null (NSG) mice

∆ DMDRMR: ↓ tumor growth

[229]

4–5-week-old male BALB/c nude mice

↑↑ miR-206: ↓ tumor size and weigh

[230]

Colon cancer

Male athymic BALB/c nude mice

∆ HAGLR: ↓ tumor growth

[231]

6-week-old female Balb/c nude mice

↑↑ miRNA-20b-5p: ↓ tumor growth

[232]

Colorectal cancer

6-week-old BALB/c athymic nude mice

↑↑ MCM3AP-AS1: ↑ tumor growth

[233]

5–6-week-old male BALB/c nude mice

↑↑ miR-142-3p: ↓ tumor growth

[234]

4–6-week-old male BALB/c athymic nude mice

↑↑ miR-875-5p: ↓ tumor growth

[236]

Esophageal squamous cell carcinoma

4–5-week-old female BALB/c athymic nude mice

↑↑ miR-1: ↓ tumor growth

[243]

Ewing sarcoma

7–8 week old nude female mice

Combination of CDK4/6 and IGF1R inhibition: ↑ survival and ↓ tumor progression

[173]

Gastric cancer

4-week-old BALB/c nude mice

↑↑ miR-1301-3p: ↑ tumor growth

[247]

6-week-old female BALB/c nude mice

∆ Linc-ROR: ↓ tumor growth

[252]

4–week-old female BALB/c nude mice

∆ GCRL1: ↓ tumor growth, tumor size, and weight

[254]

Glioblastoma

6–8 week old SCID Ncr mice

Palbociclib, CDK4/6 inhibitor: ↑ survival

[255]

6-to-8-week-old female BALB/c SCID NCr mice

Combination of CDK4/6 inhibitor, abemaciclib, with c-Met/Trk inhibitor, altiratinib was effective against GICs

[256]

Glioblastoma multiforme

BALB/C nu/nu nude mice

CDA-2 treatment: ↑ radiosensitivity which acts like the effect of miR-124

restoration and CDK4 knockdown

[258]

4–5-week-old female BALB/c nude mice

↑↑ miR-138: ↓ tumor growth

[259]

4-week-old male nude mice

∆ circMMP9: ↓ tumor growth

[260]

Glioma

5-week-old female BALB/c nude mice

Combination of TMZ and abemaciclib treatment showed antitumor efficacy

[261]

4-week-old male BALB/c nude mice

Sevoflurane treatment: ↓ tumor volume and weight via reducing HMMR-AS1

[262]

H. pylori related gastric cancer

4–6-week-old male BALB/c nude mice

↑↑ miR-101: ↓ tumor growth

[263]

Head and neck squamous cell carcinoma

nude mice

Combination of CDK4/6 inhibitor, LY2835219, and metformin: ↓ tumor growth

[265]

Hepatocellular carcinoma

4–5-week-old female BALB/C nude mice

Aminoquinol, a new CDK4/6 and PI3K/AKT inhibitor: ↓ tumor growth

[174]

6–8-week-old BALB/c, all-female nude mice

∆ circ_0001588: ↓ tumor size, volume and weight

[267]

4-week-old male BALB/c nude mice

∆ hsa_circ_0016788: ↓ tumor growth

[268]

6-week male Bl6/Rag2/GammaC double knockout nude mice

∆ CCDC144NL-AS1/WDR5 or ↑↑ miR-940: ↓ tumor growth

[270]

4-week-old female BALB/c nude mice

∆ circSP3: ↓ tumor volume and weight

[273]

BALB/c nude mice

∆ VPS9D1-AS1: ↓ tumor growth

[24]

Kaposi’s sarcoma–associated herpesvirus

4–6-week-old female BALB/c nude mice

↑↑ miR-34a-5p: ↓ tumor volume and weight

[274]

Lung cancer

female athymic BALB/c nude mice

∆ LINC01194: ↓ tumor volume and weight

[278]

6-week-old male BALB/c nude mice

↑↑ hsa_circ_0014235: ↑ DDP chemoresistance

[279]

5–6-week-old male BALB/c nude mice

↑↑ miR-613: ↓ tumor growth

[280]

4-week-old female BALB/c nude mice

↑↑ miR-340: ↓ tumor growth

[283]

4–6-week-old male BALB/c athymic nude mice

↑↑ miR-326: ↑ tumor volume and weight

[285]

4–6-week-old male BALB/c athymic nude mice

↑↑ miR-134: ↓ tumor growth

[285]

male athymic BALB/c nude mice

∆ lncSENCR: ↓ tumor growth

[291]

5–6-week-old BALB/c athymic nude mice

↑↑ miR-545: ↓ tumor volume and weight

[292]

Medulloblastoma

Balb/C nude mice

∆ HOTAIR: ↓ tumor growth

[296]

Melanoma

6–7-week-old female BALB/c nude mice

Palbociclib and GSK3326595 treatment: ↓ tumor volume

∆ PRMT5: ↓ emergence of CDK4/6 inhibitor resistance In Vivo

[298]

CrTac:NCr-Foxn1nu mice

Combination of MEK and CDK4/6 inhibitors: ↓ tumor size in NRAS mutant cells

[300]

7–8 weeks old female, pathogen free C.B 17-Scid mice

∆ CDK4 or CDK6: ↓ tumor growth

CDK4/6 inhibitor, PD0332991: ↓ tumor growth

[301]

Male C57BL/6 mice (Jackson Labs) and NSG mice

Combination of MEK and CDK4/6 inhibitors was more effective at postponing regrowth of mutant BRAF melanoma in immunocompetent versus immune-deficient mice

[302]

nude mice

∆ hsa_circ_0025039: ↓ tumor volume and weight

[304]

Nasopharyngeal carcinoma

4–week-old BALB/c nude male mice

∆ RP11-624L4.1: ↓ tumor growth

[61]

Oral squamous cell carcinoma

4–6-week-old male BALB/c nude mice

↑↑ miR-198: ↓ tumor size and volume

[312]

Osteosarcoma

6–8-week-old BALB/c nude mice

∆ 91 H: ↓ tumor growth

[317]

Ovarian cancer

6-week-old female C57BL/6 mice

Abemaciclib (inhibitor of CDK4/6) treatment: ↓ tumor growth and ↑ proinflammatory immune response

[318]

6–8-week-old female C57BL/6J mice

CDK4/6 Inhibitor, palbociclib: ↓ tumor growth by activating the immune microenvironment

[319]

Female BALB/cAnN.Cg-Foxn1nu/CrlNarl null mice

∆ COL6A3: ↓ metastasis and tumor growth via regulating CDK4/6 and p-Rb

[320]

6-week-old female athymic nude mice

CDK4/6 and PARP dual inhibitor, ZC-22: ↑ response to Cisplatin

[217]

mice

↑↑ miR-506: ↓ proliferation

[321]

Pancreatic Adenocarcinoma

6–8-week-old female athymic nude mice

∆ CDK4/6: ↓ tumor growth

[322]

Pancreatic ductal adenocarcinoma

4–5-week-old athymic nude mice

Combination of MEK and CDK4/6 inhibition: ↓ tumor growth and ↑ overall survival

[324]

Skin cancer

female BALB/C nude mice

CDK4/6 inhibitor, Rafoxanide: ↓ tumor growth

[330]

Uveal melanoma

NSG-hHGFki mice

Merestinib and Abemaciclib combination: ↓ tumor growth in NSG-hHGFki mice

[331]

6–8 week-old athymic (nu/nu) homozygous nude mice

CDK4/6 inhibition: ↑ cytostasis and ↓ tumor growth as effective as MEKi plus CDK4/6i treatment

[332]