Details of the Drug Combination

General Information of Drug Combination (ID: DCQCGGA)

• Drug Combination Name: Palbociclib + PF-562271
• Indication: Primitive neuroectodermal tumor; Status: Investigative [1]
• Component Drugs:
  Palbociclib (DMD7L94): Small molecular drug
  PF-562271 (DMSLE03): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: TC-32
  Zero Interaction Potency (ZIP) Score: 0.53
  Bliss Independence Score: 6.65
  Loewe Additivity Score: 3.97
  LHighest Single Agent (HSA) Score: 5.29

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Palbociclib

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
Schizophrenia	6A20	Terminated	[4]

Palbociclib Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Cyclin-dependent kinase 4 (CDK4)	TT0PG8F	CDK4_HUMAN	Modulator	[2]
Cyclin-dependent kinase 6 (CDK6)	TTO0FDJ	CDK6_HUMAN	Modulator	[2]

Palbociclib Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[7]

Palbociclib Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]

Palbociclib Interacts with 151 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cyclin-dependent kinase 4 (CDK4)	OT7EP05T	CDK4_HUMAN	Decreases Response To Substance	[9]
CCN family member 1 (CCN1)	OTKJBEMD	CCN1_HUMAN	Increases Expression	[6]
Kinetochore protein NDC80 homolog (NDC80)	OTS7D306	NDC80_HUMAN	Decreases Expression	[6]
Aurora kinase A (AURKA)	OTMX0HYT	AURKA_HUMAN	Decreases Expression	[6]
Monocarboxylate transporter 5 (SLC16A4)	OT1YXBKC	MOT5_HUMAN	Increases Expression	[6]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[6]
Protein Mis18-beta (OIP5)	OTI5C2DE	MS18B_HUMAN	Decreases Expression	[6]
Zinc finger protein SNAI2 (SNAI2)	OT7Y8EJ2	SNAI2_HUMAN	Increases Expression	[6]
Protein regulator of cytokinesis 1 (PRC1)	OTHD0XS0	PRC1_HUMAN	Decreases Expression	[6]
Mitotic checkpoint serine/threonine-protein kinase BUB1 (BUB1)	OT80DZMT	BUB1_HUMAN	Decreases Expression	[6]
Hyaluronan mediated motility receptor (HMMR)	OT4M0JTZ	HMMR_HUMAN	Decreases Expression	[6]
Cell division control protein 45 homolog (CDC45)	OT6NNLOD	CDC45_HUMAN	Decreases Expression	[6]
Geminin (GMNN)	OTDYKNIY	GEMI_HUMAN	Decreases Expression	[6]
Glutaminase kidney isoform, mitochondrial (GLS)	OTGOZG2M	GLSK_HUMAN	Increases Expression	[10]
G2/mitotic-specific cyclin-B2 (CCNB2)	OTIEXTDK	CCNB2_HUMAN	Decreases Expression	[6]
Serine protease 23 (PRSS23)	OT6DQAM1	PRS23_HUMAN	Increases Expression	[6]
Kinesin-like protein KIF20A (KIF20A)	OTXOQHE0	KI20A_HUMAN	Decreases Expression	[6]
Chromosome-associated kinesin KIF4A (KIF4A)	OT3UWL7D	KIF4A_HUMAN	Decreases Expression	[6]
Phospholipid-transporting ATPase ABCA1 (ABCA1)	OT94G6BQ	ABCA1_HUMAN	Increases Expression	[6]
Securin (PTTG1)	OTIMYS4W	PTTG1_HUMAN	Decreases Expression	[6]
G1/S-specific cyclin-E2 (CCNE2)	OTBBUKQQ	CCNE2_HUMAN	Decreases Expression	[11]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[12]
Transforming growth factor beta-1 proprotein (TGFB1)	OTV5XHVH	TGFB1_HUMAN	Increases Activity	[6]
Apolipoprotein E (APOE)	OTFOWL2H	APOE_HUMAN	Increases Expression	[10]
Thymidine kinase, cytosolic (TK1)	OTY5JFM1	KITH_HUMAN	Decreases Expression	[11]
Plasminogen activator inhibitor 1 (SERPINE1)	OTT0MPQ3	PAI1_HUMAN	Increases Expression	[6]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Decreases Expression	[11]
SPARC (SPARC)	OTPN90H0	SPRC_HUMAN	Increases Expression	[10]
Serine/threonine-protein kinase pim-1 (PIM1)	OTWEKXTU	PIM1_HUMAN	Decreases Expression	[12]
DNA topoisomerase 1 (TOP1)	OT51O0CF	TOP1_HUMAN	Decreases Expression	[13]
DNA topoisomerase 2-alpha (TOP2A)	OT6LPS08	TOP2A_HUMAN	Decreases Expression	[11]
Proliferating cell nuclear antigen (PCNA)	OTHZ1RIA	PCNA_HUMAN	Decreases Expression	[6]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Affects Localization	[6]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[6]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Expression	[6]
Elastin (ELN)	OTFSO7PG	ELN_HUMAN	Increases Expression	[14]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Decreases Phosphorylation	[15]
Stathmin (STMN1)	OTDJ4RV0	STMN1_HUMAN	Decreases Expression	[6]
Cadherin-2 (CDH2)	OTH0Y56P	CADH2_HUMAN	Increases Expression	[6]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Decreases Expression	[16]
Lamin-B1 (LMNB1)	OT100T3P	LMNB1_HUMAN	Decreases Expression	[6]
Ribonucleoside-diphosphate reductase large subunit (RRM1)	OTXGQOR9	RIR1_HUMAN	Decreases Expression	[6]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[17]
Cyclin-dependent kinase 2 (CDK2)	OTB5DYYZ	CDK2_HUMAN	Decreases Activity	[18]
High mobility group protein B2 (HMGB2)	OTGEGAOK	HMGB2_HUMAN	Decreases Expression	[6]
Retinoblastoma-like protein 1 (RBL1)	OTDEBFYC	RBL1_HUMAN	Decreases Expression	[16]
G1/S-specific cyclin-D3 (CCND3)	OTNKPQ22	CCND3_HUMAN	Increases Expression	[19]
M-phase inducer phosphatase 1 (CDC25A)	OTSLKKCO	MPIP1_HUMAN	Decreases Expression	[6]
M-phase inducer phosphatase 3 (CDC25C)	OTPQI71S	MPIP3_HUMAN	Decreases Expression	[6]
Ribonucleoside-diphosphate reductase subunit M2 (RRM2)	OTOB6J6R	RIR2_HUMAN	Decreases Expression	[6]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Increases Phosphorylation	[20]
Dual specificity protein kinase TTK (TTK)	OTBY1Z5H	TTK_HUMAN	Decreases Expression	[6]
DNA replication licensing factor MCM7 (MCM7)	OT6FXC6K	MCM7_HUMAN	Decreases Expression	[6]
Catenin beta-1 (CTNNB1)	OTZ932A3	CTNB1_HUMAN	Increases Expression	[6]
Receptor-type tyrosine-protein kinase FLT3 (FLT3)	OTMSRYMK	FLT3_HUMAN	Decreases Expression	[12]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[19]
Flap endonuclease 1 (FEN1)	OT6QGG7O	FEN1_HUMAN	Decreases Expression	[6]
Replication factor C subunit 5 (RFC5)	OTAD79RT	RFC5_HUMAN	Decreases Expression	[6]
Cyclin-F (CCNF)	OTJFVU43	CCNF_HUMAN	Decreases Expression	[6]
Lamina-associated polypeptide 2, isoform alpha (TMPO)	OTL68EL4	LAP2A_HUMAN	Decreases Expression	[6]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Decreases Cleavage	[15]
Ran-specific GTPase-activating protein (RANBP1)	OTQE226K	RANG_HUMAN	Decreases Expression	[10]
Proliferation marker protein Ki-67 (MKI67)	OTA8N1QI	KI67_HUMAN	Decreases Expression	[11]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[18]
Histone H3-like centromeric protein A (CENPA)	OT0NEJ4X	CENPA_HUMAN	Decreases Expression	[6]
Centromere protein F (CENPF)	OT7AG0SW	CENPF_HUMAN	Decreases Expression	[6]
DNA primase small subunit (PRIM1)	OTWWP8Y6	PRI1_HUMAN	Decreases Expression	[6]
Serine/threonine-protein kinase Nek2 (NEK2)	OT1H27HO	NEK2_HUMAN	Decreases Expression	[6]
Importin subunit alpha-1 (KPNA2)	OTU7FOE6	IMA1_HUMAN	Decreases Expression	[6]
Kinesin-like protein KIF11 (KIF11)	OTHRGLCQ	KIF11_HUMAN	Decreases Expression	[6]
Serine/threonine-protein kinase PLK1 (PLK1)	OTRZX45T	PLK1_HUMAN	Decreases Expression	[6]
DNA polymerase epsilon subunit 2 (POLE2)	OTAC9V6L	DPOE2_HUMAN	Decreases Expression	[6]
Small ribosomal subunit protein uS14 (RPS29)	OTCC1872	RS29_HUMAN	Increases Expression	[6]
Histone H4 (H4C1)	OTB71W46	H4_HUMAN	Decreases Expression	[6]
G-protein-signaling modulator 2 (GPSM2)	OT6RPMRM	GPSM2_HUMAN	Decreases Expression	[6]
Centromere-associated protein E (CENPE)	OTQ7AP04	CENPE_HUMAN	Decreases Expression	[6]
Kinesin-like protein KIF23 (KIF23)	OTY850JC	KIF23_HUMAN	Decreases Expression	[6]
Forkhead box protein M1 (FOXM1)	OT5887KR	FOXM1_HUMAN	Decreases Expression	[6]
Retinoblastoma-like protein 2 (RBL2)	OTBQSOE6	RBL2_HUMAN	Decreases Phosphorylation	[21]
Tastin (TROAP)	OTC8CE0R	TROAP_HUMAN	Decreases Expression	[6]
Cell division cycle protein 20 homolog (CDC20)	OTCOEZRV	CDC20_HUMAN	Decreases Expression	[6]
Laminin subunit beta-3 (LAMB3)	OTFPU6W8	LAMB3_HUMAN	Increases Expression	[6]
Laminin subunit gamma-2 (LAMC2)	OTJMTM72	LAMC2_HUMAN	Increases Expression	[6]
DNA polymerase alpha subunit B (POLA2)	OTTWQ73N	DPOA2_HUMAN	Decreases Expression	[6]
Transcription factor E2F2 (E2F2)	OTO75RM7	E2F2_HUMAN	Decreases Expression	[6]
Max dimerization protein 4 (MXD4)	OTUCXFRO	MAD4_HUMAN	Increases Expression	[6]
Maternal embryonic leucine zipper kinase (MELK)	OTEY2UQA	MELK_HUMAN	Decreases Expression	[6]
PCNA-associated factor (PCLAF)	OTMVIOUU	PAF15_HUMAN	Decreases Expression	[6]
Condensin complex subunit 1 (NCAPD2)	OT8VGE2O	CND1_HUMAN	Decreases Expression	[6]
Kinesin-like protein KIF14 (KIF14)	OTXHT4JM	KIF14_HUMAN	Decreases Expression	[6]
Disks large-associated protein 5 (DLGAP5)	OTWCN39U	DLGP5_HUMAN	Decreases Expression	[6]
SCL-interrupting locus protein (STIL)	OT9799VN	STIL_HUMAN	Decreases Expression	[6]
Histone-lysine N-methyltransferase EZH2 (EZH2)	OTIEHTKW	EZH2_HUMAN	Decreases Expression	[6]
Cyclin-dependent kinase inhibitor 3 (CDKN3)	OTBE3H07	CDKN3_HUMAN	Decreases Expression	[6]
Laminin subunit alpha-3 (LAMA3)	OTFME7HT	LAMA3_HUMAN	Increases Expression	[6]
Centrosomal protein of 55 kDa (CEP55)	OTGSG2PA	CEP55_HUMAN	Decreases Expression	[6]
Borealin (CDCA8)	OT17D55D	BOREA_HUMAN	Decreases Expression	[6]
PHD finger protein 19 (PHF19)	OTF6RUCR	PHF19_HUMAN	Decreases Expression	[6]
Proline/serine-rich coiled-coil protein 1 (PSRC1)	OT7MDJMN	PSRC1_HUMAN	Decreases Expression	[6]
Protein aurora borealis (BORA)	OTV2ZPKP	BORA_HUMAN	Decreases Expression	[6]
Interleukin-20 receptor subunit beta (IL20RB)	OTHFXK95	I20RB_HUMAN	Increases Expression	[6]
Protein MCM10 homolog (MCM10)	OTV0O3JN	MCM10_HUMAN	Decreases Expression	[6]
Suppressor APC domain-containing protein 2 (SAPCD2)	OTXS0EXM	SAPC2_HUMAN	Decreases Expression	[6]
Condensin-2 complex subunit G2 (NCAPG2)	OTZYENKO	CNDG2_HUMAN	Decreases Expression	[6]
Cytoskeleton-associated protein 2-like (CKAP2L)	OT4T73GG	CKP2L_HUMAN	Decreases Expression	[6]
Kinetochore protein Spc24 (SPC24)	OT1HVYV4	SPC24_HUMAN	Decreases Expression	[6]
Holliday junction recognition protein (HJURP)	OTWMV16B	HJURP_HUMAN	Decreases Expression	[6]
Protein DENND6B (DENND6B)	OTZ006UD	DEN6B_HUMAN	Increases Expression	[6]
DEP domain-containing protein 1B (DEPDC1B)	OTMVFOT1	DEP1B_HUMAN	Decreases Expression	[6]
Retinol dehydrogenase 5 (RDH5)	OTYBZHCC	RDH5_HUMAN	Increases Expression	[6]
RAD51-associated protein 1 (RAD51AP1)	OTXM7UTD	R51A1_HUMAN	Decreases Expression	[6]
Sororin (CDCA5)	OTZLCQ5U	CDCA5_HUMAN	Decreases Expression	[6]
Aurora kinase B (AURKB)	OTIY4VHU	AURKB_HUMAN	Decreases Expression	[6]
Proline-rich protein 11 (PRR11)	OT2JJ08Z	PRR11_HUMAN	Decreases Expression	[6]
Lymphokine-activated killer T-cell-originated protein kinase (PBK)	OT5Z27TW	TOPK_HUMAN	Decreases Expression	[6]
Tetratricopeptide repeat protein 14 (TTC14)	OTMTYOPF	TTC14_HUMAN	Increases Expression	[6]
Serine protease FAM111A (FAM111A)	OTVLARLG	F111A_HUMAN	Decreases Expression	[6]
Cell division cycle-associated protein 3 (CDCA3)	OTUI8QK3	CDCA3_HUMAN	Decreases Expression	[6]
Kinesin-like protein KIF2C (KIF2C)	OTJ8G3NP	KIF2C_HUMAN	Decreases Expression	[6]
BRCA1-associated RING domain protein 1 (BARD1)	OTTC0Z9Y	BARD1_HUMAN	Decreases Expression	[6]
Condensin complex subunit 3 (NCAPG)	OT1AI9EO	CND3_HUMAN	Decreases Expression	[6]
Protein PIMREG (PIMREG)	OTKC8T3E	PIMRE_HUMAN	Decreases Expression	[6]
Kinesin-like protein KIFC1 (KIFC1)	OTNQDS00	KIFC1_HUMAN	Decreases Expression	[6]
Nucleolar and spindle-associated protein 1 (NUSAP1)	OT85HIJ5	NUSAP_HUMAN	Decreases Expression	[6]
Rac GTPase-activating protein 1 (RACGAP1)	OTQE8IEH	RGAP1_HUMAN	Decreases Expression	[6]
DNA replication factor Cdt1 (CDT1)	OTVY53VG	CDT1_HUMAN	Decreases Expression	[6]
Protein-serine O-palmitoleoyltransferase porcupine (PORCN)	OT79GAY2	PORCN_HUMAN	Increases Expression	[6]
Protein FAM83D (FAM83D)	OTQWZ1UO	FA83D_HUMAN	Decreases Expression	[6]
Fanconi anemia group E protein (FANCE)	OTKRPBW1	FANCE_HUMAN	Decreases Expression	[10]
Kinetochore protein Spc25 (SPC25)	OTCAS0OH	SPC25_HUMAN	Decreases Expression	[6]
Inner centromere protein (INCENP)	OT9HFRYK	INCE_HUMAN	Decreases Expression	[6]
Anillin (ANLN)	OTXJY54C	ANLN_HUMAN	Decreases Expression	[6]
Kinesin-like protein KIF15 (KIF15)	OTJRJEXL	KIF15_HUMAN	Decreases Expression	[6]
Centromere protein M (CENPM)	OTYK9KOX	CENPM_HUMAN	Decreases Expression	[6]
Structural maintenance of chromosomes protein 4 (SMC4)	OTEJE6AG	SMC4_HUMAN	Decreases Expression	[6]
Fanconi anemia group I protein (FANCI)	OTW8E3SC	FANCI_HUMAN	Decreases Expression	[6]
Histone chaperone ASF1B (ASF1B)	OTKXX12I	ASF1B_HUMAN	Decreases Expression	[6]
Protein downstream neighbor of Son (DONSON)	OTN5HE0W	DONS_HUMAN	Decreases Expression	[6]
Carboxypeptidase A4 (CPA4)	OT66MP0F	CBPA4_HUMAN	Increases Expression	[6]
F-box only protein 5 (FBXO5)	OTTR957W	FBX5_HUMAN	Decreases Expression	[6]
Targeting protein for Xklp2 (TPX2)	OTWLJYH0	TPX2_HUMAN	Decreases Expression	[6]
Exonuclease 1 (EXO1)	OTI87RS5	EXO1_HUMAN	Decreases Expression	[6]
DNA replication complex GINS protein PSF2 (GINS2)	OT974IYI	PSF2_HUMAN	Decreases Expression	[6]
Small kinetochore-associated protein (KNSTRN)	OTYA7UXS	SKAP_HUMAN	Decreases Expression	[6]
Transforming acidic coiled-coil-containing protein 3 (TACC3)	OTRNEZTA	TACC3_HUMAN	Decreases Expression	[10]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Response To Substance	[22]
Cyclin-dependent kinase 4 inhibitor B (CDKN2B)	OTAG24N1	CDN2B_HUMAN	Decreases Response To Substance	[9]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Decreases Response To Substance	[22]
G1/S-specific cyclin-E1 (CCNE1)	OTLD7UID	CCNE1_HUMAN	Decreases Response To Substance	[22]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Increases Response To Substance	[22]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Decreases Response To Substance	[22]

Indication(s) of PF-562271

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]

PF-562271 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Focal adhesion kinase 1 (FAK)	TTON5IT	FAK1_HUMAN	Inhibitor	[23]

References

• [1] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2017
• [3] ClinicalTrials.gov (NCT01723774) PD 0332991 and Anastrozole for Stage 2 or 3 Estrogen Receptor Positive and HER2 Negative Breast Cancer. U.S. National Institutes of Health.
• [4] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [5] ClinicalTrials.gov (NCT00666926) Study Of PF-00562271, Including Patients With Pancreatic, Head And Neck, Prostatic Neoplasms. U.S. National Institutes of Health.
• [6] Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
• [7] Efflux transporters at the blood-brain barrier limit delivery and efficacy of cyclin-dependent kinase 4/6 inhibitor palbociclib (PD-0332991) in an orthotopic brain tumor model. J Pharmacol Exp Ther. 2015 Nov;355(2):264-71.
• [8] Progress with palbociclib in breast cancer: latest evidence and clinical considerations. Ther Adv Med Oncol. 2017 Feb;9(2):83-105.
• [9] p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells. Neuro Oncol. 2012 Jul;14(7):870-81. doi: 10.1093/neuonc/nos114. Epub 2012 Jun 18.
• [10] Biological specificity of CDK4/6 inhibitors: dose response relationship, in vivo signaling, and composite response signature. Oncotarget. 2017 Jul 4;8(27):43678-43691. doi: 10.18632/oncotarget.18435.
• [11] Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004 Nov;3(11):1427-38.
• [12] Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6. Blood. 2016 Jun 9;127(23):2890-902. doi: 10.1182/blood-2015-11-683581. Epub 2016 Apr 20.
• [13] Synergism of cyclin-dependent kinase inhibitors with camptothecin derivatives in small cell lung cancer cell lines. Molecules. 2014 Feb 17;19(2):2077-88. doi: 10.3390/molecules19022077.
• [14] Retinoblastoma protein modulates the inverse relationship between cellular proliferation and elastogenesis. J Biol Chem. 2011 Oct 21;286(42):36580-91. doi: 10.1074/jbc.M111.269944. Epub 2011 Aug 31.
• [15] CDK4/6 inhibition antagonizes the cytotoxic response to anthracycline therapy. Cell Cycle. 2012 Jul 15;11(14):2747-55. doi: 10.4161/cc.21127. Epub 2012 Jul 15.
• [16] Proliferative suppression by CDK4/6 inhibition: complex function of the retinoblastoma pathway in liver tissue and hepatoma cells. Gastroenterology. 2010 May;138(5):1920-30. doi: 10.1053/j.gastro.2010.01.007. Epub 2010 Jan 25.
• [17] Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
• [18] Pharmacologic inhibition of CDK4/6: mechanistic evidence for selective activity or acquired resistance in acute myeloid leukemia. Blood. 2007 Sep 15;110(6):2075-83. doi: 10.1182/blood-2007-02-071266. Epub 2007 May 30.
• [19] Therapeutic CDK4/6 inhibition in breast cancer: key mechanisms of response and failure. Oncogene. 2010 Jul 15;29(28):4018-32. doi: 10.1038/onc.2010.154. Epub 2010 May 17.
• [20] CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers. Cancer Res. 2014 Jul 15;74(14):3947-58. doi: 10.1158/0008-5472.CAN-13-2923. Epub 2014 Jul 1.
• [21] Dual inhibition of CDK4/Rb and PI3K/AKT/mTOR pathways by ON123300 induces synthetic lethality in mantle cell lymphomas. Leukemia. 2016 Jan;30(1):86-93. doi: 10.1038/leu.2015.185. Epub 2015 Jul 15.
• [22] Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer. Clin Cancer Res. 2011 Mar 15;17(6):1591-602. doi: 10.1158/1078-0432.CCR-10-2307. Epub 2011 Jan 28.
• [23] Inhibition of focal adhesion kinase by PF-562,271 inhibits the growth and metastasis of pancreatic cancer concomitant with altering the tumor microenvironment. Mol Cancer Ther. 2011 Nov;10(11):2135-45.