Toward Targeted Therapies in Oesophageal Cancers: An Overview

Abstract

Oesophageal cancer is one of the leading causes of cancer-related death worldwide. Oesophageal cancer occurs as squamous cell carcinoma (ESCC) or adenocarcinoma (EAC). Prognosis for patients with either ESCC or EAC is poor, with less than 20% of patients surviving more than 5 years after diagnosis. A major progress has been made in the development of biomarker-driven targeted therapies against breast and lung cancers, as well as melanoma. However, precision oncology for patients with oesophageal cancer is still virtually non-existent. In this review, we outline the recent advances in oesophageal cancer profiling and clinical trials based on targeted therapies in this disease.

Keywords: cancer; oesophagus; therapeutics.

Figure 1

Barplot summarizing frequent genomic alterations found in ESCC and EAC (only alterations >10% of samples in at least one histology are represented). These data highlight differences in the pattern of genomic alterations between ESCC and EAC. Three ESCC molecular subtypes are defined based on the genomic alteration profile. Data from the TCGA, Firehose Legacy (n = 186). Abbreviations: EAC: oesophageal adenocarcinoma; ESCC: oesophageal squamous cell carcinoma; TP53: Tumor Protein P53; CDKN2A: Cyclin Dependent Kinase Inhibitor 2A; PIK3CA: Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha; TP63: Tumor Protein P63; SOX: Sry-type HMG box; KMT2D: Lysine Methyltransferase 2D; NFE2L2: Nuclear factor erythroid 2-related factor 2; KDM6A: Lysine Demethylase 6A; NOTCH1: Notch homolog 1, translocation-associated; ZNF750: Zinc Finger Protein 750; RB1: Retinoblastoma; SMARCA4: SWI/SNF-Related, Matrix-Associated, Actin-Dependent Regulator Of Chromatin, Subfamily A, Member 4; FAT1: FAT Atypical Cadherin 1; NOTCH3: Notch Receptor 3; TGFBR2: Transforming Growth Factor Beta Receptor 2; SMAD4: SMAD family member 4; FAT2: FAT Atypical Cadherin 2; FBXW7: F-Box And WD Repeat Domain Containing 7; NAV3: Neuron Navigator 3; GATA4: GATA Binding Protein 4; GATA6: GATA Binding Protein 6; KRAS: Kirsten rat sarcoma virus; DCDC1: Doublecortin Domain Containing 1; PBMR1: Polybromo 1; TENMR3: Teneurin Transmembrane Protein 3; ARID1A: AT-Rich Interaction Domain 1A; ERBB2: Erb-B2 Receptor Tyrosine Kinase 2; CTNNB1: Catenin Beta 1.

Figure 2

Scheme summarizing the signaling pathways that have been targeted the most frequently in oesophageal cancers. The different targeted therapies used in clinical trials to treat esophageal cancers are shown in red.