Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Cristina Díaz del Arco
 -- 2469 2024-02-28 17:21:57 |
2 references update and layout
Fanny Huang
 Meta information modification 2469 2024-02-29 04:39:43 |

Video Upload Options

We provide professional Video Production Services to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Díaz Del Arco, C.; Fernández Aceñero, M.J.; Ortega Medina, L. Gastric Cancer in the Molecular Era. Encyclopedia. Available online: https://encyclopedia.pub/entry/55673 (accessed on 22 December 2024).
Díaz Del Arco C, Fernández Aceñero MJ, Ortega Medina L. Gastric Cancer in the Molecular Era. Encyclopedia. Available at: https://encyclopedia.pub/entry/55673. Accessed December 22, 2024.
Díaz Del Arco, Cristina, María Jesús Fernández Aceñero, Luis Ortega Medina. "Gastric Cancer in the Molecular Era" Encyclopedia, https://encyclopedia.pub/entry/55673 (accessed December 22, 2024).
Díaz Del Arco, C., Fernández Aceñero, M.J., & Ortega Medina, L. (2024, February 28). Gastric Cancer in the Molecular Era. In Encyclopedia. https://encyclopedia.pub/entry/55673
Díaz Del Arco, Cristina, et al. "Gastric Cancer in the Molecular Era." Encyclopedia. Web. 28 February, 2024.
Gastric Cancer in the Molecular Era
Edit
This entry is adapted from the peer-reviewed paper 10.3390/ijms25052649

Gastric cancer (GC) is a heterogeneous disease, often diagnosed at advanced stages, with a 5-year survival rate of approximately 20%. Numerous molecular alterations have been identified in GC, leading to various molecular classifications, such as those developed by The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG). 

gastric cancer molecular prognosis

1. Introduction

Gastric cancer (GC) ranks as the fifth most common cancer worldwide, and is the third leading cause of cancer-related deaths. It is an aggressive disease, often diagnosed at advanced stages, with a 5-year survival rate of less than 30% [1][2].
In terms of classification, GC is a heterogeneous disease with multiple clinical, histological, and molecular variables influencing disease presentation and patient prognosis [3][4]. Geographical differences have been observed between Asian and Western countries, with GC being more prevalent in Asian regions. In fact, some high-incidence countries have implemented screening strategies that have improved early detection and patient outcomes [5][6][7]. Furthermore, geographic variations related to clinical, histological, prognostic, surgical, and treatment response factors have been noted [8][9][10].
Clinically, GC can be divided into proximal and distal types, each with distinct epidemiological characteristics. Proximal GC is associated with obesity, gastroesophageal reflux, and Barrett’s esophagus, while the more prevalent distal type is linked to Helicobacter pylori infections, the male gender, smoking, and dietary habits [1][11][12].
From a macroscopic perspective, GC can be classified using the Paris classification for superficial lesions, the Borrmann classification for advanced GC (stage pT2 or higher), or the Japanese Society of Endoscopy classification, encompassing both early and advanced GC [13][14][15].
With respect to histological features, notable classifications include the Laurén and the World Health Organization (WHO) systems [16][17]. Laurén’s classification, established in 1965 as a histoclinical classification, categorizes GC into intestinal and diffuse types. Intestinal GC forms tubules and may include papillary or solid structures, occurs in older patients, and is associated with H. pylori infection and environmental factors. It develops through the carcinogenic process of chronic gastritis—intestinal metaplasia—dysplasia [18]. In contrast, diffuse GC is composed of loosely cohesive cells, potentially displaying signet ring morphology, appears in younger patients, and is induced by active inflammation or genetic factors. Previous studies have shown that this classification correlates with patient prognosis, treatment response, and the molecular characteristics of GC [8]. On the other hand, the WHO classification is more complex, morphology-based, and identifies the following four main types of GC: tubular, papillary, poorly cohesive, and mucinous [19]. This classification has shown a lower correlation with non-histological factors [20]. It should be noted that both classifications establish a "mixed" subtype.
Regarding GC treatment, surgery remains the only curative option for GC [21]. Endoscopic techniques can be employed in early stages, while more advanced stages, prevalent in Western countries, require a total or subtotal gastrectomy with lymphadenectomy [22]. For non-surgical patients, chemotherapy is the main therapeutic approach [23]. Approved targeted drugs include antiangiogenics (anti-VEGFR-2) and anti-HER2 agents [24][25]. Additionally, the approval of pembrolizumab for solid tumors with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR) included GC cases [26][27]. The indication for immunotherapy also depends on PD-L1 expression or the tumor mutational burden (TMB) [28]. Therefore, the only established and broadly available biomarkers for GC treatment are HER2 amplification, MSI-H, and PD-L1 expression [29]. The therapeutic arsenal for GC is limited when compared to other tumor types, and current therapies have not significantly improved patient prognosis [30][31].
In terms of molecular characteristics, technological advancements in recent years have allowed the identification of multiple molecular alterations in various types of tumors [32]. Among these, alterations with prognostic or therapeutic value have significantly impacted clinical practice in tumors such as lung or breast cancer, enabling personalized treatment, improving patient outcomes, and reducing the side effects associated with conventional treatment [33][34].
In GC, multiple studies have analyzed its genetic, epigenetic, transcriptomic, proteomic, or metabolomic profiles, revealing numerous molecular changes and dysregulated pathways, some of which carry prognostic and/or therapeutic significance [35][36][37][38][39][40][41]. The synthesis of this information has given rise to several molecular classifications, with notable examples being those published by The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) [42][43]. Despite these efforts, the practical impact of these classifications on clinical practice remains limited, primarily due to the complexity of their implementation. Beyond these pivotal studies, various authors have proposed alternative molecular classifications of GC that require external validation in other cohorts and the identification of surrogate markers for their application. Consequently, there is an urgent need to reach a consensus on molecular categories, establish easily detectable subgroups, and identify optimal surrogate markers for each molecular subtype.

2. Gastric Cancer Characterization, Prognosis, and Management in the Molecular Era

As previously mentioned, recent technological advancements have propelled cancer research into the molecular era. Comprehensive genetic, transcriptomic, and proteomic analyses are now possible, resulting in vast databases of molecular changes, including mutations, copy number variants, epigenetic alterations, gene expression profiles, or disrupted pathways across various tumor types. This wealth of information has enabled the identification of molecular alterations with prognostic and therapeutic significance. Prognostic alterations allow for personalized patient management, improving the cost-effectiveness of treatment. Meanwhile, predictive molecular alterations have transformed cancer treatment from a generic approach to an individualized approach. Targeted drugs have enhanced patient prognosis, often with fewer side effects and better tolerance than conventional chemotherapy [44].

2.1. The Molecular Era: Recent Advances in Molecular Techniques

Among the technological advances that have impacted the molecular characterization of cancer in the last decade, microarrays and second- or next-generation sequencing platforms (NGS) stand out. Microarrays allow the detection of molecular alterations at the DNA, RNA, or protein level [45][46][47]. They are primarily applied in research studies, although some commercial microarray-based platforms are used in clinical routine, mainly in breast cancer [48][49]. NGS techniques, which have been implemented in clinical practices in institutions worldwide, are typically employed for DNA sequencing. They facilitate the simultaneous analysis of multiple samples, either at the whole genome or whole exome level, or through the utilization of targeted panels containing dozens of genes of interest. These techniques have been refined, automated, and modified to allow for the analysis of RNA or epigenetic alterations. In GC, NGS and microarrays have played a pivotal role in elucidating the landscape of molecular alterations [50][51][52][53]. However, in the daily practice of GC, these techniques do not present significant applications because the necessary biomarkers are currently analyzed using immunohistochemistry (IHC) and in situ hybridization methods. NGS could be useful for determining the TMB, or as a complementary technique for assessing MSI status [54][55][56][57].
In the early 2010s, third-generation sequencing techniques emerged, enabling sequencing at a single-molecule level. Despite their potential, these techniques have not been integrated into clinical practice, and their utilization in research studies remains limited. Advantages over second-generation sequencing methods include the fact that they do not require sample pre-amplification and can read longer fragments of DNA, but the error rate is generally higher (10–15%) [58][59][60][61].
Lastly, another interesting molecular approach that has garnered attention in recent years is single-cell sequencing (SCS), which, using second- or third-generation methodologies, enables the analysis of DNA, RNA, or methylome at the single-cell level [62][63][64][65]. Its main advantage lies in its ability to scrutinize the molecular profile of cell subclones, thereby offering significant potential for evaluating tumor heterogeneity, refining the personalization of patient management, and enhancing the monitoring of treatment response and resistance detection [66][67]. Furthermore, SCS requires a small sample size, thus making it suitable for analyzing circulating tumor cells in liquid biopsy specimens [68]. However, these techniques have not yet been implemented in clinical routine and require technical refinement, standardization, and cost reduction to have a practical impact [69][70]. In GC, research in this area is in its early stages, but promising results have been obtained [71][72][73].

2.2. Main Molecular Alterations in Gastric Cancer

Multiple molecular alterations and dysregulated pathways have been identified in GC. Notably, mutations in the TP53 and CDH1 genes are prominent [74][75]. TP53 mutation is the most common in GC, occurring in over 50% of cases, and is often associated with chromosomal instability and an increased expression of cell-cycle progression genes [76][77]. While the TP53 mutation has been correlated with a worse prognosis in other tumors, its significance in GC remains unclear [75][78][79][80]. This uncertainty may stem from the specific impact of different mutations on the function of the p53 protein, concomitant molecular alterations, or treatment effects [75][81]. Additionally, most studies have focused on the p53 protein rather than the gene, with some exceptions [75][77][82][83]. As for CDH1, it encodes for E-cadherin, a transmembrane glycoprotein responsible for maintaining cell–cell adhesion [84]. Germline mutations in CDH1 are associated with hereditary diffuse GC syndrome, which increases the risk of diffuse GC and lobular breast carcinoma [85]. In sporadic GC cases, mutations and the abnormal methylation of CDH1 are predominantly found in diffuse GC [86][87]. Other key mutations in GC include those within the ARID1A, PIK3CA, or BRCA2 genes [88][89][90].
Regarding copy number alterations, the amplification of genes involved in tyrosine kinase receptor pathways, such as FGFR2, HER2, EGFR, or MET, stand out [91][92][93][94]. Among these genes, HER2 amplification has significant clinical implications, serving as an indication for treatment with trastuzumab in advanced HER2-positive GC patients [95][96]. HER2 amplification occurs in 10–15% of patients with advanced GC, with a higher prevalence in intestinal-type GC and a lower prevalence in diffuse GC [97][98][99]. The most frequent copy number variation is the amplification of FGFR2, which is observed in 15% of patients and associated with high-grade tumors and a poorer prognosis [93].
Finally, the main dysregulated pathways in GC include those related to genome integrity, cell adhesion, chromatin remodeling, cell motility and cytoskeletal structure, Wnt signaling, and tyrosine kinase receptors [74].

2.3. Current Treatment of Gastric Cancer

As for the management of GC, surgery remains the only curative option, and most resectable tumors are treated with total or subtotal gastrectomy associated with D2 lymphadenectomy. Early stage tumors meeting certain criteria may undergo endoscopic procedures, such as endoscopic mucosal resection or endoscopic submucosal dissection [100]. The assessment of tumor depth, size, grade, and the presence of ulceration is crucial to determine the suitability of these techniques [101].
Surgery for GC typically forms part of a multimodal treatment, with the two following options, depending on the context: surgery followed by adjuvant chemotherapy or perioperative therapy. Regarding the surgical procedure, according to the European Society for Medical Oncology (ESMO) guidelines, T1 tumors can be treated with partial gastrectomy and D1 lymphadenectomy, while for IB-III disease, total or subtotal gastrectomy with D2 lymphadenectomy is recommended [101]. Perioperative chemotherapy has become the standard of care, supported by findings from clinical trials which have been conducted since the 2000s, demonstrating a survival benefit for patients undergoing this approach [102][103][104]. ESMO guidelines advocate for the pre- and post-operative administration of FLOT regimen (5-FU, leucovorin, oxaliplatin, and docetaxel) in patients who can tolerate it [101]. The choice of the chemotherapy regimen may vary depending on the guideline, and the role of radiotherapy as an adjunct is still under investigation [105][106][107].
The main innovations in the surgical treatment of GC include the use of laparoscopy, which has been shown to be non-inferior to open surgery in both Asian and Western countries, and robot-assisted gastrectomy [108][109][110][111].
Regarding non-surgical cases, it is worth noting that, despite the detection of numerous molecular alterations and the development of multiple molecular classifications in GC, the clinical application of this information lags behind other cancers. For instance, breast cancer has successfully integrated molecular classification into daily practice, surpassing the practical impact of traditional histological features. In lung cancer, multiple targetable alterations have been identified, leading to recommendations for testing as many as nine molecular biomarkers and PD-L1 expression in all adenocarcinomas and in squamous cell carcinomas that meet certain criteria [112]. As a final example, in endometrial cancer, molecular and histopathological features have been integrated to develop a new FIGO staging system with prognostic and therapeutic value, which has been in effect since 2023 [113].
Contrastingly, in unresectable GC, the main therapeutic approach continues to be conventional chemotherapy, typically involving a platinum-fluoropyrimidine doublet [114]. Nonetheless, many patients develop resistance to this treatment, which often leads to adverse effects [115][116][117].
The administration of targeted therapy has the potential to enhance the specificity and efficacy of oncological treatment, while mitigating adverse effects [118]. As drawbacks, the effectiveness of these therapies is heavily reliant on the molecular profile of the tumor at a given time, and they are not entirely devoid of toxicity [44][119]. According to the latest National Comprehensive Cancer Network guidelines, the main targeted therapies approved for advanced GC include anti-HER2 agents (trastuzumab and fam-trastuzumab deruxtecan-nxki), anti-VEGFR-2 agents (ramucirumab), and immunotherapy (nivolumab, pembrolizumab and dostarlimab-gxly) [120]. Anti-HER2 therapy is indicated in HER2-amplified GC, and immunotherapy may be indicated in cases with MSI-H, PD-L1 overexpression, or a high TMB [120]. However, the latest ESMO guidelines only include PD-L1 expression and MSI-H as indications for immunotherapy [101]. Lastly, tumors with NTRK1, NTRK2, or NTRK3 gene fusions may be treated with entrectinib and larotrectinib, although such cases are exceptionally rare in GC, with only one case published so far [121].

2.4. Gastric Cancer: Therapeutic Advances and Challenges

Early GC has demonstrated favorable outcomes for decades, with survival rates of over 90% with surgical treatment [122][123]. However, in Western countries, the lack of widespread screening techniques coupled with mild and nonspecific symptoms has lead to over 80% of patients being diagnosed at advanced stages [124]. Despite advancements in molecular biology and personalized therapy, the prognosis for advanced GC has seen limited improvement [125]. Even in resectable cases, the recurrence rates range from 14–80%, often exceeding 40% within the first years following surgery [126][127]. The addition of neoadjuvant therapy in surgical cases has slightly improved patient prognosis, but studies report recurrence rates exceeding 30% [128][129][130]. Unresectable cases present a dismal prognosis, with median overall survival rates ranging from 11 to 14 months, and 5-year survival rates of less than 30% [131][132][133][134]. Notably, patients eligible for targeted therapy or immunotherapy exhibit significantly higher survival rates overall [135][136]. However, numerous authors highlight the need to refine patient selection for these treatments, enhance drug efficacy, identify new therapeutic targets, and overcome treatment resistance [137][138][139][140].
The modest impact of the aforementioned advancements on the prognosis and management of advanced GC and the scarcity of therapeutic targets could be due to the heterogeneity that characterizes this tumor, both phenotypically and molecularly [3][4][141]. This heterogeneity is also evident at the intratumoral and tumor microenvironmental levels, as demonstrated by recent single-cell studies [142][143]. Additionally, molecular heterogeneity exists among primary tumors, lymph node metastases, and distant metastatic sites [144][145][146]. Understanding spatial and temporal heterogeneity, both phenotypically and molecularly, at primary and metastatic sites holds promise for improving prognosis and treatment outcomes for GC patients.
New potential treatment strategies for GC encompass perioperative targeted therapy or immunotherapy, personalized treatment guided by molecular tumor characterization, the utilization of trastuzumab conjugates, and the development of new anti-HER2 agents. Additionally, ongoing studies are investigating novel therapeutic approaches, such as Claudin 18.2 targeted therapy or FGFR, MET, and EGFR inhibitors [147][148].
In summary, these circumstances highlight the need for enhancing patient stratification in both clinical trials and practice. Additionally, identifying new biomarkers and improving the currently available drugs is crucial to expand the range and effectiveness of targeted therapies for GC and translate the progress seen in other tumors to GC.

References

  1. Rawla, P.; Barsouk, A. Epidemiology of gastric cancer: Global trends, risk factors and prevention. Prz. Gastroenterol. 2019, 14, 26–38.
  2. Ilic, M.; Ilic, I. Epidemiology of stomach cancer. World J. Gastroenterol. 2022, 28, 1187–1203.
  3. Sexton, R.E.; Al Hallak, M.N.; Uddin, M.H.; Diab, M.; Azmi, A.S. Gastric Cancer Heterogeneity and Clinical Outcomes. Technol. Cancer Res. Treat. 2020, 19, 1533033820935477.
  4. Gullo, I.; Carneiro, F.; Oliveira, C.; Almeida, G.M. Heterogeneity in Gastric Cancer: From Pure Morphology to Molecular Classifications. Pathobiology 2018, 85, 50–63.
  5. Russo, A.E.; Strong, V.E. Gastric Cancer Etiology and Management in Asia and the West. Annu. Rev. Med. 2019, 70, 353–367.
  6. Rahman, R.; Asombang, A.W.; Ibdah, J.A. Characteristics of gastric cancer in Asia. World J. Gastroenterol. 2014, 20, 4483–4490.
  7. Yashima, K.; Shabana, M.; Kurumi, H.; Kawaguchi, K.; Isomoto, H. Gastric Cancer Screening in Japan: A Narrative Review. J. Clin. Med. 2022, 11, 4337.
  8. Díaz del Arco, C.; Ortega Medina, L.; Estrada Muñoz, L.; García Gómez de las Heras, S.; Fernández Aceñero, M.J. Is there still a place for conventional histopathology in the age of molecular medicine? Laurén classification, inflammatory infiltration and other current topics in gastric cancer diagnosis and prognosis. Histol. Histopathol. 2021, 36, 587–613.
  9. Ye, X.S.; Yu, C.; Aggarwal, A.; Reinhard, C. Genomic alterations and molecular subtypes of gastric cancers in Asians. Chin. J. Cancer 2016, 35, 42.
  10. Kim, J.; Sun, C.L.; Mailey, B.; Prendergast, C.; Artinyan, A.; Bhatia, S.; Pigazzi, A.; Ellenhorn, J.D.I. Race and ethnicity correlate with survival in patients with gastric adenocarcinoma. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2010, 21, 152–160.
  11. Arnold, M.; Park, J.Y.; Camargo, M.C.; Lunet, N.; Forman, D.; Soerjomataram, I. Is gastric cancer becoming a rare disease? A global assessment of predicted incidence trends to 2035. Gut 2020, 69, 823–829.
  12. Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA. Cancer J. Clin. 2018, 68, 394–424.
  13. Sano, T.; Kodera, Y. Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer 2011, 14, 101–112.
  14. The Paris endoscopic classification of superficial neoplastic lesions: Esophagus, stomach, and colon: November 30 to December 1, 2002. Gastrointest. Endosc. 2003, 58, S3–S43.
  15. Song, X.H.; Zhang, W.H.; Kai-Liu; Chen, X.L.; Zhao, L.Y.; Chen, X.Z.; Kun-Yang; Zhou, Z.G.; Hu, J.K. Prognostic impact of Borrmann classification on advanced gastric cancer: A retrospective cohort from a single institution in western China. World J. Surg. Oncol. 2020, 18, 204.
  16. Laurén, P. The two histological main types of gastric carcinoma: Diffuse and so-alled intestinal-type arcinoma. An attempt at a histo-clinical classification. Acta Pathol. Microbiol. Scand. 1965, 64, 31–49.
  17. Yang, H.; Yang, W.J.; Hu, B. Gastric epithelial histology and precancerous conditions. World J. Gastrointest. Oncol. 2022, 14, 396–412.
  18. Correa, P.; Piazuelo, M.B. The gastric precancerous cascade. J. Dig. Dis. 2012, 13, 2–9.
  19. Kushima, R. The updated WHO classification of digestive system tumours-gastric adenocarcinoma and dysplasia. Pathologe 2022, 43, 8–15.
  20. Agnes, A.; Estrella, J.S.; Badgwell, B. The significance of a nineteenth century definition in the era of genomics: Linitis plastica. World J. Surg. Oncol. 2017, 15, 123.
  21. Tegels, J.J.W.; De Maat, M.F.G.; Hulsewé, K.W.E.; Hoofwijk, A.G.M.; Stoot, J.H. Improving the outcomes in gastric cancer surgery. World J. Gastroenterol. 2014, 20, 13692–13704.
  22. Smyth, E.C.; Nilsson, M.; Grabsch, H.I.; van Grieken, N.C.; Lordick, F. Gastric cancer. Lancet 2020, 396, 635–648.
  23. Wagner, A.D.; Syn, N.L.X.; Moehler, M.; Grothe, W.; Yong, W.P.; Tai, B.C.; Ho, J.; Unverzagt, S. Chemotherapy for advanced gastric cancer. Cochrane Database Syst. Rev. 2017, 8, CD004064.
  24. Hironaka, S. Anti-angiogenic therapies for gastric cancer. Asia Pac. J. Clin. Oncol. 2019, 15, 208–217.
  25. Zhu, Y.; Zhu, X.; Wei, X.; Tang, C.; Zhang, W. HER2-targeted therapies in gastric cancer. Biochim. Biophys. Acta Rev. Cancer 2021, 1876, 188549.
  26. Salati, M.; Orsi, G.; Smyth, E.; Beretta, G.; De Vita, F.; Di Bartolomeo, M.; Fanotto, V.; Lonardi, S.; Morano, F.; Pietrantonio, F.; et al. Gastric cancer: Translating novels concepts into clinical practice. Cancer Treat. Rev. 2019, 79, 101889.
  27. Boyiadzis, M.M.; Kirkwood, J.M.; Marshall, J.L.; Pritchard, C.C.; Azad, N.S.; Gulley, J.L. Significance and implications of FDA approval of pembrolizumab for biomarker-defined disease. J. Immunother. Cancer 2018, 6, 35.
  28. Peixoto, R.D.; Mathias-Machado, M.C.; Jácome, A.; Gil, M.; Fogacci, J.; Sodré, B.; Passarini, T.; Chaves, A.; Diniz, P.H.; Lino, F.; et al. PD-L1 testing in advanced gastric cancer-what physicians who treat this disease must know-a literature review. J. Gastrointest. Oncol. 2023, 14, 1560–1575.
  29. Nakamura, Y.; Kawazoe, A.; Lordick, F.; Janjigian, Y.Y.; Shitara, K. Biomarker-targeted therapies for advanced-stage gastric and gastro-oesophageal junction cancers: An emerging paradigm. Nat. Rev. Clin. Oncol. 2021, 18, 473–487.
  30. Agnarelli, A.; Vella, V.; Samuels, M.; Papanastasopoulos, P.; Giamas, G. Incorporating Immunotherapy in the Management of Gastric Cancer: Molecular and Clinical Implications. Cancers 2022, 14, 4378.
  31. Del Prete, C.; Muthiah, A.; Almhanna, K. Does tumor profile in gastric and gastroesophageal (GE) junction cancer justify off-label use of targeted therapy?—A narrative review. Ann. Transl. Med. 2020, 8, 1110.
  32. Sarhadi, V.K.; Armengol, G. Molecular Biomarkers in Cancer. Biomolecules 2022, 12, 1021.
  33. Saller, J.J.; Boyle, T.A. Molecular Pathology of Lung Cancer. Cold Spring Harb. Perspect. Med. 2022, 12, a037812.
  34. Zhang, X. Molecular Classification of Breast Cancer: Relevance and Challenges. Arch. Pathol. Lab. Med. 2023, 147, 46–51.
  35. Guo, J.; Yu, W.; Su, H.; Pang, X. Genomic landscape of gastric cancer: Molecular classification and potential targets. Sci. China. Life Sci. 2017, 60, 126–137.
  36. Rostami-Nejad, M.; Rezaei-Tavirani, M.; Mansouri, V.; Akbari, Z.; Abdi, S. Impact of proteomics investigations on gastric cancer treatment and diagnosis. Gastroenterol. Hepatol. Bed Bench 2019, 12, S1.
  37. Yuan, Q.; Deng, D.; Pan, C.; Ren, J.; Wei, T.; Wu, Z.; Zhang, B.; Li, S.; Yin, P.; Shang, D. Integration of transcriptomics, proteomics, and metabolomics data to reveal HER2-associated metabolic heterogeneity in gastric cancer with response to immunotherapy and neoadjuvant chemotherapy. Front. Immunol. 2022, 13, 951137.
  38. Pužar Dominkuš, P.; Hudler, P. Mutational Signatures in Gastric Cancer and Their Clinical Implications. Cancers 2023, 15, 3788.
  39. Carino, A.; Graziosi, L.; Marchianò, S.; Biagioli, M.; Marino, E.; Sepe, V.; Zampella, A.; Distrutti, E.; Donini, A.; Fiorucci, S. Analysis of Gastric Cancer Transcriptome Allows the Identification of Histotype Specific Molecular Signatures with Prognostic Potential. Front. Oncol. 2021, 11, 663771.
  40. Kadam, W.; Wei, B.; Li, F. Metabolomics of Gastric Cancer. Adv. Exp. Med. Biol. 2021, 1280, 291–301.
  41. Tang, S.Y.; Zhou, P.J.; Meng, Y.; Zeng, F.R.; Deng, G.T. Gastric cancer: An epigenetic view. World J. Gastrointest. Oncol. 2022, 14, 90–109.
  42. Bass, A.J.; Thorsson, V.; Shmulevich, I.; Reynolds, S.M.; Miller, M.; Bernard, B.; Hinoue, T.; Laird, P.W.; Curtis, C.; Shen, H.; et al. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014, 513, 202–209.
  43. Cristescu, R.; Lee, J.; Nebozhyn, M.; Kim, K.M.; Ting, J.C.; Wong, S.S.; Liu, J.; Yue, Y.G.; Wang, J.; Yu, K.; et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat. Med. 2015, 21, 449–456.
  44. Min, H.Y.; Lee, H.Y. Molecular targeted therapy for anticancer treatment. Exp. Mol. Med. 2022, 54, 1670–1694.
  45. Bumgarner, R. Overview of DNA microarrays: Types, applications, and their future. Curr. Protoc. Mol. Biol. 2013, 101, 22.1.1–22.1.11.
  46. Sealfon, S.C.; Chu, T.T. RNA and DNA microarrays. Methods Mol. Biol. 2011, 671, 3–34.
  47. Sutandy, F.X.R.; Qian, J.; Chen, C.S.; Zhu, H. Overview of protein microarrays. Curr. Protoc. Protein Sci. 2013, 72, 27.1.1–27.1.16.
  48. Kao, K.J.; Chang, K.M.; Hsu, H.C.; Huang, A.T. Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: Implications for treatment optimization. BMC Cancer 2011, 11, 143.
  49. Yao, K.; Tong, C.Y.; Cheng, C. A framework to predict the applicability of Oncotype DX, MammaPrint, and E2F4 gene signatures for improving breast cancer prognostic prediction. Sci. Rep. 2022, 12, 2211.
  50. D’Angelo, G.; Di Rienzo, T.; Ojetti, V. Microarray analysis in gastric cancer: A review. World J. Gastroenterol. 2014, 20, 11972–11976.
  51. Dang, Y.; Wang, Y.C.; Huang, Q.J. Microarray and next-generation sequencing to analyse gastric cancer. Asian Pac. J. Cancer Prev. 2014, 15, 8033–8039.
  52. Verma, R.; Sharma, P.C. Next generation sequencing-based emerging trends in molecular biology of gastric cancer. Am. J. Cancer Res. 2018, 8, 207–225.
  53. Businello, G.; Galuppini, F.; Fassan, M. The impact of recent next generation sequencing and the need for a new classification in gastric cancer. Best Pract. Res. Clin. Gastroenterol. 2021, 50–51, 101730.
  54. Ku, G.Y. Next generation sequencing in gastric or gastroesophageal adenocarcinoma. Transl. Gastroenterol. Hepatol. 2020, 5, 56.
  55. Puliga, E.; Corso, S.; Pietrantonio, F.; Giordano, S. Microsatellite instability in Gastric Cancer: Between lights and shadows. Cancer Treat. Rev. 2021, 95, 102175.
  56. Duan, Y.; Xu, D. Microsatellite instability and immunotherapy in gastric cancer: A narrative review. Precis. Cancer Med. 2023, 6.
  57. Ke, L.; Li, S.; Huang, D. The predictive value of tumor mutation burden on survival of gastric cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis. Int. Immunopharmacol. 2023, 124, 110986.
  58. Liu, Q.; Chen, Q.; Zhang, Z.; Peng, S.; Liu, J.; Pang, J.; Jia, Z.; Xi, H.; Li, J.; Chen, L.; et al. Identification of rare thalassemia variants using third-generation sequencing. Front. Genet. 2023, 13, 1076035.
  59. Ambardar, S.; Gupta, R.; Trakroo, D.; Lal, R.; Vakhlu, J. High Throughput Sequencing: An Overview of Sequencing Chemistry. Indian J. Microbiol. 2016, 56, 394–404.
  60. Athanasopoulou, K.; Boti, M.A.; Adamopoulos, P.G.; Skourou, P.C.; Scorilas, A. Third-Generation Sequencing: The Spearhead towards the Radical Transformation of Modern Genomics. Life 2021, 12, 30.
  61. Xiao, T.; Zhou, W. The third generation sequencing: The advanced approach to genetic diseases. Transl. Pediatr. 2020, 9, 163–173.
  62. Liao, Y.; Liu, Z.; Zhang, Y.; Lu, P.; Wen, L.; Tang, F. High-throughput and high-sensitivity full-length single-cell RNA-seq analysis on third-generation sequencing platform. Cell Discov. 2023, 9, 5.
  63. Chang, L.; Deng, E.; Wang, J.; Zhou, W.; Ao, J.; Liu, R.; Su, D.; Fan, X. Single-cell third-generation sequencing-based multi-omics uncovers gene expression changes governed by ecDNA and structural variants in cancer cells. Clin. Transl. Med. 2023, 13, e1351.
  64. Wen, L.; Tang, F. Recent advances in single-cell sequencing technologies. Precis. Clin. Med. 2022, 5, pbac002.
  65. Anaparthy, N.; Ho, Y.J.; Martelotto, L.; Hammell, M.; Hicks, J. Single-Cell Applications of Next-Generation Sequencing. Cold Spring Harb. Perspect. Med. 2019, 9, a026898.
  66. Melnekoff, D.T.; Laganà, A. Single-Cell Sequencing Technologies in Precision Oncology. Adv. Exp. Med. Biol. 2022, 1361, 269–282.
  67. Zhang, Y.; Wang, D.; Peng, M.; Tang, L.; Ouyang, J.; Xiong, F.; Guo, C.; Tang, Y.; Zhou, Y.; Liao, Q.; et al. Single-cell RNA sequencing in cancer research. J. Exp. Clin. Cancer Res. 2021, 40, 81.
  68. Xu, J.; Liao, K.; Yang, X.; Wu, C.; Wu, W.; Han, S. Using single-cell sequencing technology to detect circulating tumor cells in solid tumors. Mol. Cancer 2021, 20, 104.
  69. Chen, S.; Zhou, Z.; Li, Y.; Du, Y.; Chen, G. Application of single-cell sequencing to the research of tumor microenvironment. Front. Immunol. 2023, 14, 1285540.
  70. Pfisterer, U.; Bräunig, J.; Brattås, P.; Heidenblad, M.; Karlsson, G.; Fioretos, T. Single-cell sequencing in translational cancer research and challenges to meet clinical diagnostic needs. Genes. Chromosomes Cancer 2021, 60, 504–524.
  71. Deng, G.; Zhang, X.; Chen, Y.; Liang, S.; Liu, S.; Yu, Z.; Lü, M. Single-cell transcriptome sequencing reveals heterogeneity of gastric cancer: Progress and prospects. Front. Oncol. 2023, 13, 1074268.
  72. Bian, S.; Wang, Y.; Zhou, Y.; Wang, W.; Guo, L.; Wen, L.; Fu, W.; Zhou, X.; Tang, F. Integrative single-cell multiomics analyses dissect molecular signatures of intratumoral heterogeneities and differentiation states of human gastric cancer. Natl. Sci. Rev. 2023, 10, nwad094.
  73. Wang, R.; Dang, M.; Harada, K.; Han, G.; Wang, F.; Pool Pizzi, M.; Zhao, M.; Tatlonghari, G.; Zhang, S.; Hao, D.; et al. Single-cell dissection of intratumoral heterogeneity and lineage diversity in metastatic gastric adenocarcinoma. Nat. Med. 2021, 27, 141–151.
  74. Katona, B.W.; Rustgi, A.K. Gastric Cancer Genomics: Advances and Future Directions. Cell. Mol. Gastroenterol. Hepatol. 2017, 3, 211–217.
  75. Deng, W.; Hao, Q.; Vadgama, J.; Wu, Y. Wild-Type TP53 Predicts Poor Prognosis in Patients with Gastric Cancer. J. Cancer Sci. Clin. Ther. 2021, 5, 134–153.
  76. Donehower, L.A.; Soussi, T.; Korkut, A.; Liu, Y.; Schultz, A.; Cardenas, M.; Li, X.; Babur, O.; Hsu, T.K.; Lichtarge, O.; et al. Integrated Analysis of TP53 Gene and Pathway Alterations in The Cancer Genome Atlas. Cell Rep. 2019, 28, 1370–1384.e5.
  77. Graziano, F.; Fischer, N.W.; Bagaloni, I.; Di Bartolomeo, M.; Lonardi, S.; Vincenzi, B.; Perrone, G.; Fornaro, L.; Ongaro, E.; Aprile, G.; et al. TP53 Mutation Analysis in Gastric Cancer and Clinical Outcomes of Patients with Metastatic Disease Treated with Ramucirumab/Paclitaxel or Standard Chemotherapy. Cancers 2020, 12, 2049.
  78. Gu, J.; Zhou, Y.; Huang, L.; Ou, W.; Wu, J.; Li, S.; Xu, J.; Feng, J.; Liu, B. TP53 mutation is associated with a poor clinical outcome for non-small cell lung cancer: Evidence from a meta-analysis. Mol. Clin. Oncol. 2016, 5, 705–713.
  79. Meric-Bernstam, F.; Zheng, X.; Shariati, M.; Damodaran, S.; Wathoo, C.; Brusco, L.; Demirhan, M.E.; Tapia, C.; Eterovic, A.K.; Basho, R.K.; et al. Survival Outcomes by TP53 Mutation Status in Metastatic Breast Cancer. JCO Precis. Oncol. 2018, 2018, 1–15.
  80. Olivier, M.; Hollstein, M.; Hainaut, P. TP53 mutations in human cancers: Origins, consequences, and clinical use. Cold Spring Harb. Perspect. Biol. 2010, 2, a001008.
  81. Kennedy, M.C.; Lowe, S.W. Mutant p53: It’s not all one and the same. Cell Death Differ. 2022, 29, 983–987.
  82. Yildirim, M.; Kaya, V.; Demirpence, O.; Gunduz, S.; Bozcuk, H. Prognostic significance of p53 in gastric cancer: A meta- analysis. Asian Pac. J. Cancer Prev. 2015, 16, 327–332.
  83. Fenoglio-Preiser, C.M.; Wang, J.; Stemmermann, G.N.; Noffsinger, A. TP53 and gastric carcinoma: A review. Hum. Mutat. 2003, 21, 258–270.
  84. Liu, X.; Chu, K.M. E-cadherin and gastric cancer: Cause, consequence, and applications. Biomed Res. Int. 2014, 2014, 637308.
  85. Garziera, M.; Canzonieri, V.; Cannizzaro, R.; Geremia, S.; Caggiari, L.; De Zorzi, M.; Maiero, S.; Orzes, E.; Perin, T.; Zanussi, S.; et al. Identification and characterization of CDH1 germline variants in sporadic gastric cancer patients and in individuals at risk of gastric cancer. PLoS ONE 2013, 8, e77305.
  86. Cho, S.Y.; Park, J.W.; Liu, Y.; Park, Y.S.; Kim, J.H.; Yang, H.; Um, H.; Ko, W.R.; Lee, B.I.; Kwon, S.Y.; et al. Sporadic Early-Onset Diffuse Gastric Cancers Have High Frequency of Somatic CDH1 Alterations, but Low Frequency of Somatic RHOA Mutations Compared with Late-Onset Cancers. Gastroenterology 2017, 153, 536–549.
  87. Machado, J.C.; Oliveira, C.; Carvalho, R.; Soares, P.; Berx, G.; Caldas, C.; Seruca, R.; Carneiro, F.; Sobrinho-Simöes, M. E-cadherin gene (CDH1) promoter methylation as the second hit in sporadic diffuse gastric carcinoma. Oncogene 2001, 20, 1525–1528.
  88. Kim, Y.S.; Jeong, H.; Choi, J.W.; Oh, H.; Lee, J.H. Unique characteristics of ARID1A mutation and protein level in gastric and colorectal cancer: A meta-analysis. Saudi J. Gastroenterol. 2017, 23, 268–274.
  89. Buckley, K.H.; Niccum, B.A.; Maxwell, K.N.; Katona, B.W. Gastric Cancer Risk and Pathogenesis in BRCA1 and BRCA2 Carriers. Cancers 2022, 14, 5953.
  90. Kim, J.W.; Lee, H.S.; Nam, K.H.; Ahn, S.; Kim, J.W.; Ahn, S.H.; Park, D.J.; Kim, H.H.; Lee, K.W. PIK3CA mutations are associated with increased tumor aggressiveness and Akt activation in gastric cancer. Oncotarget 2017, 8, 90948–90958.
  91. Morishita, A.; Gong, J.; Masaki, T. Targeting receptor tyrosine kinases in gastric cancer. World J. Gastroenterol. 2014, 20, 4536–4545.
  92. Yamaguchi, H.; Nagamura, Y.; Miyazaki, M. Receptor Tyrosine Kinases Amplified in Diffuse-Type Gastric Carcinoma: Potential Targeted Therapies and Novel Downstream Effectors. Cancers 2022, 14, 3750.
  93. Kim, H.S.; Kim, J.H.; Jang, H.J. Pathologic and prognostic impacts of FGFR2 amplification in gastric cancer: A meta-analysis and systemic review. J. Cancer 2019, 10, 2560–2567.
  94. Park, C.K.; Park, J.S.; Kim, H.S.; Rha, S.Y.; Hyung, W.J.; Cheong, J.H.; Noh, S.H.; Lee, S.K.; Lee, Y.C.; Huh, Y.m.; et al. Receptor tyrosine kinase amplified gastric cancer: Clinicopathologic characteristics and proposed screening algorithm. Oncotarget 2016, 7, 72099–72112.
  95. Roviello, G.; Catalano, M.; Iannone, L.F.; Marano, L.; Brugia, M.; Rossi, G.; Aprile, G.; Antonuzzo, L. Current status and future perspectives in HER2 positive advanced gastric cancer. Clin. Transl. Oncol. 2022, 24, 981–996.
  96. Xue, C.; Xu, Y.H. Trastuzumab combined chemotherapy for the treatment of HER2-positive advanced gastric cancer: A systematic review and meta-analysis of randomized controlled trial. Medicine 2022, 101, E29992.
  97. Rüschoff, J.; Hanna, W.; Bilous, M.; Hofmann, M.; Osamura, R.Y.; Penault-Llorca, F.; Van De Vijver, M.; Viale, G. HER2 testing in gastric cancer: A practical approach. Mod. Pathol. 2012, 25, 637–650.
  98. Lago, N.M.; Villar, M.V.; Ponte, R.V.; Nallib, I.A.; Carrera Alvarez, J.J.; Antúnez López, J.R.; López, R.L.; Padin Iruegas, M.E. Impact of HER2 status in resected gastric or gastroesophageal junction adenocarcinoma in a Western population. Ecancermedicalscience 2020, 14, 1020.
  99. Wang, H.B.; Liao, X.F.; Zhang, J. Clinicopathological factors associated with HER2-positive gastric cancer: A meta-analysis. Medicine 2017, 96, e8437.
  100. Kim, G.H.; Jung, H.Y. Endoscopic Resection of Gastric Cancer. Gastrointest. Endosc. Clin. N. Am. 2021, 31, 563–579.
  101. Lordick, F.; Carneiro, F.; Cascinu, S.; Fleitas, T.; Haustermans, K.; Piessen, G.; Vogel, A.; Smyth, E.C. Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2022, 33, 1005–1020.
  102. Cunningham, D.; Allum, W.H.; Stenning, S.P.; Thompson, J.N.; Van de Velde, C.J.H.; Nicolson, M.; Scarffe, J.H.; Lofts, F.J.; Falk, S.J.; Iveson, T.J.; et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N. Engl. J. Med. 2006, 355, 11–20.
  103. Al-Batran, S.E.; Homann, N.; Pauligk, C.; Goetze, T.O.; Meiler, J.; Kasper, S.; Kopp, H.G.; Mayer, F.; Haag, G.M.; Luley, K.; et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): A randomised, phase 2/3 trial. Lancet 2019, 393, 1948–1957.
  104. Ychou, M.; Boige, V.; Pignon, J.P.; Conroy, T.; Bouché, O.; Lebreton, G.; Ducourtieux, M.; Bedenne, L.; Fabre, J.M.; Saint-Aubert, B.; et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: An FNCLCC and FFCD multicenter phase III trial. J. Clin. Oncol. 2011, 29, 1715–1721.
  105. Ajani, J.A.; Bentrem, D.J.; Besh, S.; D’Amico, T.A.; Das, P.; Denlinger, C.; Fakih, M.G.; Fuchs, C.S.; Gerdes, H.; Glasgow, R.E.; et al. Gastric cancer, version 2.2013: Featured updates to the NCCN Guidelines. J. Natl. Compr. Canc. Netw. 2013, 11, 531–546.
  106. Eom, S.S.; Choi, W.; Eom, B.W.; Park, S.H.; Kim, S.J.; Kim, Y.I.; Yoon, H.M.; Lee, J.Y.; Kim, C.G.; Kim, H.K.; et al. A Comprehensive and Comparative Review of Global Gastric Cancer Treatment Guidelines. J. Gastric Cancer 2022, 22, 3–23.
  107. Yu, J. Il Role of Adjuvant Radiotherapy in Gastric Cancer. J. Gastric Cancer 2023, 23, 194–206.
  108. van Boxel, G.I.; Ruurda, J.P.; van Hillegersberg, R. Robotic-assisted gastrectomy for gastric cancer: A European perspective. Gastric Cancer 2019, 22, 909–919.
  109. Hakkenbrak, N.A.G.; Jansma, E.P.; van der Wielen, N.; van der Peet, D.L.; Straatman, J. Laparoscopic versus open distal gastrectomy for gastric cancer: A systematic review and meta-analysis. Surgery 2022, 171, 1552–1561.
  110. Lou, S.; Yin, X.; Wang, Y.; Zhang, Y.; Xue, Y. Laparoscopic versus open gastrectomy for gastric cancer: A systematic review and meta-analysis of randomized controlled trials. Int. J. Surg. 2022, 102, 106678.
  111. Guerrini, G.P.; Esposito, G.; Magistri, P.; Serra, V.; Guidetti, C.; Olivieri, T.; Catellani, B.; Assirati, G.; Ballarin, R.; Di Sandro, S.; et al. Robotic versus laparoscopic gastrectomy for gastric cancer: The largest meta-analysis. Int. J. Surg. 2020, 82, 210–228.
  112. Pennell, N.A.; Arcila, M.E.; Gandara, D.R.; West, H. Biomarker Testing for Patients with Advanced Non-Small Cell Lung Cancer: Real-World Issues and Tough Choices. Am. Soc. Clin. Oncol. Educ. book. Am. Soc. Clin. Oncol. Annu. Meet. 2019, 39, 531–542.
  113. Berek, J.S.; Matias-Guiu, X.; Creutzberg, C.; Fotopoulou, C.; Gaffney, D.; Kehoe, S.; Lindemann, K.; Mutch, D.; Concin, N.; Berek, J.S.; et al. FIGO staging of endometrial cancer: 2023. Int. J. Gynaecol. Obstet. 2023, 162, 383–394.
  114. Arai, H.; Iwasa, S.; Boku, N.; Kawahira, M.; Yasui, H.; Masuishi, T.; Muro, K.; Minashi, K.; Hironaka, S.; Fukuda, N.; et al. Fluoropyrimidine with or without platinum as first-line chemotherapy in patients with advanced gastric cancer and severe peritoneal metastasis: A multicenter retrospective study. BMC Cancer 2019, 19, 652.
  115. Marin, J.J.G.; Al-Abdulla, R.; Lozano, E.; Briz, O.; Bujanda, L.; Banales, J.M.; Macias, R.I.R. Mechanisms of Resistance to Chemotherapy in Gastric Cancer. Anticancer. Agents Med. Chem. 2016, 16, 318–334.
  116. Yakir, R.; Luna, K.; Marc, W.; Tamar, S.; Avraham, R.; Ayala, H. The toxicity and outcomes of continuous 5-fluorouracil/cisplatin-based chemotherapy followed by chemoradiation in patients with resected high-risk gastric cancer: Results of a single institute. Ann. Acad. Med. Singapore 2008, 37, 200–203.
  117. Rivera, F.; Vega-Villegas, M.E.; López-Brea, M.F. Chemotherapy of advanced gastric cancer. Cancer Treat. Rev. 2007, 33, 315–324.
  118. Zhou, Z.; Li, M. Targeted therapies for cancer. BMC Med. 2022, 20, 90.
  119. Liu, S.; Kurzrock, R. Toxicity of targeted therapy: Implications for response and impact of genetic polymorphisms. Cancer Treat. Rev. 2014, 40, 883–891.
  120. Ajani, J.A.; D’Amico, T.A.; Bentrem, D.J.; Chao, J.; Cooke, D.; Corvera, C.; Das, P.; Enzinger, P.C.; Enzler, T.; Fanta, P.; et al. Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J. Natl. Compr. Cancer Netw. 2022, 20, 167–192.
  121. Shinozaki-Ushiku, A.; Ishikawa, S.; Komura, D.; Seto, Y.; Aburatani, H.; Ushiku, T. The first case of gastric carcinoma with NTRK rearrangement: Identification of a novel ATP1B-NTRK1 fusion. Gastric Cancer 2020, 23, 944–947.
  122. Tan, Y.K.; Fielding, J.W.L. Early diagnosis of early gastric cancer. Eur. J. Gastroenterol. Hepatol. 2006, 18, 821–829.
  123. Onodera, H.; Tokunaga, A.; Yoshiyuki, T.; Kiyama, T.; Kato, S.; Matsukura, N.; Masuda, G.; Tajiri, T. Surgical outcome of 483 patients with early gastric cancer: Prognosis, postoperative morbidity and mortality, and gastric remnant cancer. Hepatogastroenterology 2004, 51, 82–85.
  124. Chiarello, M.M.; Fico, V.; Pepe, G.; Tropeano, G.; Adams, N.J.; Altieri, G.; Brisinda, G. Early gastric cancer: A challenge in Western countries. World J. Gastroenterol. 2022, 28, 693–703.
  125. Liu, W.; Xu, J.; Zhang, C. Clinical usefulness of gastric adenocarcinoma predictive long intergenic noncoding RNA in human malignancies: A meta-analysis. Pathol. Res. Pract. 2019, 215, 152387.
  126. Kang, W.M.; Meng, Q.B.; Yu, J.C.; Ma, Z.Q.; Li, Z.T. Factors associated with early recurrence after curative surgery for gastric cancer. World J. Gastroenterol. 2015, 21, 5934.
  127. Aurello, P.; Petrucciani, N.; Antolino, L.; Giulitti, D.; D’Angelo, F.; Ramacciato, G. Follow-up after curative resection for gastric cancer: Is it time to tailor it? World J. Gastroenterol. 2017, 23, 3379–3387.
  128. Mokadem, I.; Dijksterhuis, W.P.M.; van Putten, M.; Heuthorst, L.; de Vos-Geelen, J.M.; Haj Mohammad, N.; Nieuwenhuijzen, G.A.P.; van Laarhoven, H.W.M.; Verhoeven, R.H.A. Recurrence after preoperative chemotherapy and surgery for gastric adenocarcinoma: A multicenter study. Gastric Cancer 2019, 22, 1263.
  129. Nakauchi, M.; Vos, E.; Tang, L.H.; Gonen, M.; Janjigian, Y.Y.; Ku, G.Y.; Ilson, D.H.; Maron, S.B.; Yoon, S.S.; Brennan, M.F.; et al. Outcomes of Neoadjuvant Chemotherapy for Clinical Stages 2 and 3 Gastric Cancer Patients: Analysis of Timing and Site of Recurrence. Ann. Surg. Oncol. 2021, 28, 4829–4838.
  130. Lavacchi, D.; Fancelli, S.; Buttitta, E.; Vannini, G.; Guidolin, A.; Winchler, C.; Caliman, E.; Vannini, A.; Giommoni, E.; Brugia, M.; et al. Perioperative Tailored Treatments for Gastric Cancer: Times Are Changing. Int. J. Mol. Sci. 2023, 24, 4877.
  131. Sato, S.; Oshima, Y.; Matsumoto, Y.; Seto, Y.; Yamashita, H.; Hayano, K.; Kano, M.; Ono, H.A.; Mitsumori, N.; Fujisaki, M.; et al. The new prognostic score for unresectable or recurrent gastric cancer treated with nivolumab: A multi-institutional cohort study. Ann. Gastroenterol. Surg. 2021, 5, 794–803.
  132. Kuhara, Y.; Ninomiya, M.; Hirahara, S.; Doi, H.; Kenji, S.; Toyota, K.; Yano, R.; Kobayashi, H.; Hashimoto, Y.; Yokoyama, Y.; et al. A long-term survival case of unresectable gastric cancer with multidisciplinary therapy including immunotherapy and abscopal effect. Int. Cancer Conf. J. 2020, 9, 193–198.
  133. Hu, H.M.; Tsai, H.J.; Ku, H.Y.; Lo, S.S.; Shan, Y.S.; Chang, H.C.; Chao, Y.; Chen, J.S.; Chen, S.C.; Chiang, C.J.; et al. Survival outcomes of management in metastatic gastric adenocarcinoma patients. Sci. Rep. 2021, 11, 23142.
  134. Schütte, K.; Schulz, C.; Middelberg-Bisping, K. Impact of gastric cancer treatment on quality of life of patients. Best Pract. Res. Clin. Gastroenterol. 2021, 50–51.
  135. Ha, G.-Y.; Yang, S.-H.; Kang, H.-J.; Lee, H.-L.; Kim, J.; Kim, Y.-J.; Yu, H.-J.; Lee, J.-I.; Jin, S.-H. Comparison of survival outcomes according of patients with metastatic gastric cancer receiving trastuzumab with systemic chemotherapy. Korean J. Clin. Oncol. 2020, 16, 63–70.
  136. Zhang, Z.; Liu, Z.; Chen, Z. Comparison of Treatment Efficacy and Survival Outcomes Between Asian and Western Patients with Unresectable Gastric or Gastro-Esophageal Adenocarcinoma: A Systematic Review and Meta-Analysis. Front. Oncol. 2022, 12, 831207.
  137. Apicella, M.; Corso, S.; Giordano, S. Targeted therapies for gastric cancer: Failures and hopes from clinical trials. Oncotarget 2017, 8, 57654–57669.
  138. Skórzewska, M.; Gęca, K.; Polkowski, W.P. A Clinical Viewpoint on the Use of Targeted Therapy in Advanced Gastric Cancer. Cancers 2023, 15, 5490.
  139. Attia, H.; Smyth, E. Evolving therapies in advanced oesophago-gastric cancers and the increasing role of immunotherapy. Expert Rev. Anticancer Ther. 2021, 21, 535–546.
  140. Sato, Y.; Okamoto, K.; Kawano, Y.; Kasai, A.; Kawaguchi, T.; Sagawa, T.; Sogabe, M.; Miyamoto, H.; Takayama, T. Novel Biomarkers of Gastric Cancer: Current Research and Future Perspectives. J. Clin. Med. 2023, 12, 4646.
  141. Gao, J.P.; Xu, W.; Liu, W.T.; Yan, M.; Zhu, Z.G. Tumor heterogeneity of gastric cancer: From the perspective of tumor-initiating cell. World J. Gastroenterol. 2018, 24, 2567–2581.
  142. Wang, B.; Zhang, Y.; Qing, T.; Xing, K.; Li, J.; Zhen, T.; Zhu, S.; Zhan, X. Comprehensive analysis of metastatic gastric cancer tumour cells using single-cell RNA-seq. Sci. Rep. 2021, 11, 1141.
  143. Chen, J.; Liu, K.; Luo, Y.; Kang, M.; Wang, J.; Chen, G.; Qi, J.; Wu, W.; Wang, B.; Han, Y.; et al. Single-Cell Profiling of Tumor Immune Microenvironment Reveals Immune Irresponsiveness in Gastric Signet-Ring Cell Carcinoma. Gastroenterology 2023, 165, 88–103.
  144. Lee, H.H.; Kim, S.Y.; Jung, E.S.; Yoo, J.; Kim, T.M. Mutation heterogeneity between primary gastric cancers and their matched lymph node metastases. Gastric Cancer 2019, 22, 323–334.
  145. Jiang, H.; Yu, D.; Yang, P.; Guo, R.; Kong, M.; Gao, Y.; Yu, X.; Lu, X.; Fan, X. Revealing the transcriptional heterogeneity of organ-specific metastasis in human gastric cancer using single-cell RNA Sequencing. Clin. Transl. Med. 2022, 12, e730.
  146. Lee, J.E.; Kim, K.T.; Shin, S.J.; Cheong, J.H.; Choi, Y.Y. Genomic and evolutionary characteristics of metastatic gastric cancer by routes. Br. J. Cancer 2023, 129, 672–682.
  147. Ishii, T.; Shitara, K. Trastuzumab deruxtecan and other HER2-targeting agents for the treatment of HER2-positive gastric cancer. Expert Rev. Anticancer Ther. 2021, 21, 1193–1201.
  148. Guan, W.L.; He, Y.; Xu, R.H. Gastric cancer treatment: Recent progress and future perspectives. J. Hematol. Oncol. 2023, 16, 57.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Oncology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Cristina Díaz del Arco
,
María Jesús Fernández Aceñero
,
Luis Ortega Medina
View Times: 554
Entry Collection: Gastrointestinal Disease
Revisions: 2 times (View History)
Update Date: 29 Feb 2024
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback