Cancer Genetics and Epigenetics, 2025, Vol.13, No.2, 62-76 http://medscipublisher.com/index.php/cge 71 Figure 3 Schematic representation of characteristic molecular features of EAC (Adopted from Hoppe et al., 2021) Image caption: Top, sequence of histological states towards EAC. Bottom, list of molecular categories and key genes that are typically altered; GERD, gastro-esophageal reflux disease; ITH, intratumoral heterogeneity; RTK, receptor tyrosine kinase; SCNA, somatic genome copy number alteration; SNV: single-nucleotide variant; WGD, whole genome doubling (Adopted from Hoppe et al., 2021) 10 Challenges and Future Directions 10.1 Limitations of current genomic research At present, there are quite a few difficulties in the genetic research on esophageal adenocarcinoma (EAC). A major problem is that the genes of tumors vary greatly, which makes it very troublesome to find universal diagnostic indicators and therapeutic targets. For instance, studies have found that the key gene mutations in patients with EAC vary and the genes are unstable. Therefore, it is difficult to find therapeutic targets that are effective for all patients (Frankell et al., 2018; Kumar et al., 2021). Moreover, under the influence of treatments such as chemotherapy, genes keep changing, which makes it more difficult for people to figure out the development process of EAC and the causes of drug resistance (Murugaesu et al., 2015). Another deficiency is that the sample size of many studies is not large enough and may not be able to cover all the genetic differences of EAC (Stachler et al., 2018). In addition, integrating and analyzing data from multiple aspects such as genes, gene
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