Table 3.

Biomarkers for chemo-resistance to first-line chemotherapy in advanced ovarian cancer.

Chemotherapy	Macromolecule	Biomarker	Source	Cellular mechanism	Clinical phenotype	Chemo-resistance	References
Platinum-based drug/Alkylating agent	Protein	Lung resistance protein (LRP) ↑	Tissue	Increases drug efflux	Non-responder	Intrinsic	115
Doxorubicin, cisplatin and paclitaxel	mRNA	Human epidermal growth factor receptor 2 (HER-2) ↑	Cell line	Increases drug efflux and increases drug metabolism	Responder	N/A	116,117
Paclitaxel	RNA	Inactive X chromosome-specific Transcripts (XIST) ↓	Cell line and tissue	Reactivates resistance-specific genes on inactive X chromosome in the absence of XIST RNA.	Non-responder	Acquired	118
Cisplatin	Protein	Cycloxegenase-2 (COX-2) ↑	Tissue	Increases proliferation and inhibits apoptosis	Non-responder	Intrinsic	119
Cisplatin	Protein	P-glycoprotein (Pgp) ↑	Tissue	Increases drug efflux	Non-responder	Intrinsic	119
Cisplatin	mRNA	Trophinin (TRO) ↑	Cell line	Homophilic adhesion molecule involved in blastocyst implantation	Responder	N/A	120
Carboplatin and cyclophosphamide	Protein	Excision repair cross-complementation group 1 (ERCC-1) ↑	Tissue	Increases DNA repair	Non-responder	Intrinsic	121
Platinum-based drug and paclitaxel	Protein	Vascular endothelial growth factor (VEGF) ↑	Ascites	Increases tumour angiogenesis	Non-responder	Intrinsic	122
Platinum-based drug and paclitaxel	Protein	Tumour necrosis factor alpha (TNFα) ↑	Ascites	Increases inflammation	Non-responder	Intrinsic	122
Paclitaxel	Protein	Endoplasmic reticulum resident oxidoreductase 57 (ERp57) ↑	Cell line	Increases protein folding under stress and inhibits apoptosis	Non-responder	Acquired	123
Platinum-based drug and cyclophosphamide or paclitaxel	mRNA	Mesothelin (MSLN) ↑	Tissue	Alters the time spent by cytotoxic drugs in the peritoneal cavity or changes the tumour microenvironment of ovarian cancer patients; therefore inhibiting the effects of cytotoxic drugs	Non-responder	Intrinsic	124
Cisplatin	DNA	Insulin-like growth factor I receptor (IGF1R) ↑	Cell line	Inhibits apoptosis	Non-responder	Acquired	125–127
Cisplatin	DNA	Phosphatidylinositol-3-OH kinase (PIK) ↑	Cell line	Inhibits apoptosis	Non-responder	Acquired	125–127
Platinum-based-drug	DNA	Cyclin E (CCNE1) ↑	Tissue	Increases cell proliferation	Non-responder	Intrinsic	128
Paclitaxel	Protein	Heterogeneous nuclear riboprotein A2 (hnRNPA2) ↓	Cell line	Increased cell stability	Non-responder	Acquired	129,130
Paclitaxel	Protein	Rho GDP dissociation inhibitor (GDI 2) ↓	Cell line	Increases invasion	Non-responder	Acquired	129,131
Cisplatin	Protein	Pyruvate kinase-M2 (PKM2) ↓	Cell line	Increases drug inactivation	Non-responder	Acquired	132,133
Cisplatin	Protein	Heat shock protein D1 (HSP-D1) ↑	Cell line	Inhibits apoptosis	Non-responder	Acquired	132,134
Cisplatin	Protein	Hypoxia up-regulated protein 1 precursor (HYOU1) ↑	Cell line	Inhibits apoptosis	Non-responder	Acquired	132,135
Cisplatin	Protein	Isoform 1 of collagen XII alpha-1 chain (COL12A1) ↓	Cell line	Increases tumour angiogenesis and invasion	Non-responder	Acquired	132,136,137
Cisplatin	Protein	Calnexin (CNX) ↑	Cell line	Inhibits apoptosis	Non-responder	Acquired	132,138
Cisplatin	Protein	High mobility group protein B1 (HMGB1) ↑	Cell line	Reduces DNA damage	Non-responder	Acquired	132,139
Cisplatin	Protein	Lung resistance protein (LRP) ↑	Cell line	Increases drug efflux	Non-responder	Acquired	104,121
Cisplatin	Protein	Nestin (NES)↑	Tissue	Increases tumour angiogenesis	Non-responder	Intrinsic	130,131
Cisplatin	Protein	Activated leukocyte cell adhesion molecule (ALCAM)↑	Cell line	Increased interaction with pro-growth NFκB pathway	Non-responder	Acquired	132
Cisplatin	Protein	A-kinase anchoring protein 12 (AKAP12) ↑	Cell line	Inhibits apoptosis	Non-responder	Acquired	132
Carboplatin	Protein	Steroid receptor coactivator 3 (SRC-3) ↑	Tissue	Increases cell survival	Non-responder	Intrinsic	114,133
Cisplatin	Protein	Pro-alpha1(XI) chain (COL11A1) ↑	Cell line	Increases invasion	Non-responder	Acquired	134,135
Paclitaxel	mRNA	Chitinase 3-like 1 (CHI3L1) ↑	Tissue	Inhibits apoptosis	Non-responder	Intrinsic	136
Platinum-based drug and paclitaxel	mRNA	Insulin-like growth factor 2 mRNA-binding protein (IGF2BP) ↑	Tissue	Increases tumour proliferation	Non-responder	Intrinsic	137
Platinum-based and paclitaxel	mRNA	Lin-28 Homolog B (Lin28B) ↑	Tissue	Acts as oncogene by blocking let-7 miRNA biogenesis and subsequent depression of let-7 miRNA target genes	Non-responder	Intrinsic	139
Platinum-based drug	Protein	Leptin (LEP) ↑	Ascites	Inhibits apoptosis	Non-responder	Intrinsic	138,139
Cisplatin paclitaxel	Protein	Midkine (MK) ↑	Tissue	Increases cytotoxicity	Responder	N/A	140
Paclitaxel	Protein	Musashi-2 (MSI2) ↑	Cell line	Increases drug efflux	Non-responder	Acquired	141
Platinum-based	Protein	RAN Binding Protein 1 (RANBP1) ↓	Tissue	Increases tumour proliferation, decreases drug binding to DNA and inhibits apoptosis	Non-responder	Intrinsic	142
Platinum-based drug	Protein	Actinin Alpha 4 (ACTN4) ↑	Tissue	Increases invasion	Non-responder	Intrinsic	142
Platinum-based drug	Protein	Keratin 19 (KRT19) ↑	Tissue	Increases invasion	Non-responder	Intrinsic	142,143
Platinum-based drug	Protein	Lactate dehydrogenase A-like 6A (LDHAL6A) ↑	Tissue	Increases anaerobic metabolism	Non-responder	Intrinsic	142,144
Platinum-based drug	Protein	Thiopurine S-methyltransferase (TPMT) ↓	Tissue	Decreases metabolism of drug	Responder	N/A	142,145
Platinum-based and paclitaxel	Protein	Mesothelium vascular cell adhesion molecule-1 (VCAM-1) ↑	Serum	Increases invasion	Non-responder	Acquired	146,147
Platinum-based drug	Protein	Epithelial cell adhesion molecule (EpCam) ↑	Tissue	Inhibits apoptosis	Non-responder	Acquired	148
Platinum-based drug	mRNA and protein	Forkhead box M1 (FOXM1) ↑	Tissue	Increases cell-cycle progression, response to DNA damage	Non-responder	Intrinsic	149,150
Carboplatin	mRNA and protein	Keratin 5 (KRT5) ↑	Cell line, tissue and ascites	Increases cytoskeletal stability	Non-responder	Acquired	151
Cisplatin	mRNA	Colony-stimulating-factor-1 receptor (CSF-1R) ↑	Cell line	Inhibits apoptosis	Non-responder	Acquired	152
Cisplatin	mRNA	3-Oxoacid CoA transferase 1 (OXCT1) ↓	Cell line	Inhibits apoptosis	Non-responder	Acquired	153,154