Cancers

Editorial

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Open AccessEditorial

Recent Research on Gastrointestinal Carcinoma

by Giulia Rovesti, Giorgia Marisi and Andrea Casadei-Gardini

Cancers 2021, 13(2), 333; https://doi.org/10.3390/cancers13020333 - 18 Jan 2021

Cited by 1 | Viewed by 1358

Abstract

This series of 10 articles (eight original articles and two reviews) is presented by international leaders in gastrointestinal cancer research [...] Full article

(This article belongs to the Special Issue Recent Research on Gastrointestinal Carcinoma)

Research

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12 pages, 1940 KiB

Open AccessArticle

Endoscopic Images by a Single-Shot Multibox Detector for the Identification of Early Cancerous Lesions in the Esophagus: A Pilot Study

by Yao-Kuang Wang, Hao-Yi Syu, Yi-Hsun Chen, Chen-Shuan Chung, Yu Sheng Tseng, Shinn-Ying Ho, Chien-Wei Huang, I-Chen Wu and Hsiang-Chen Wang

Cancers 2021, 13(2), 321; https://doi.org/10.3390/cancers13020321 - 17 Jan 2021

Cited by 29 | Viewed by 3140

Abstract

Diagnosis of early esophageal neoplasia, including dysplasia and superficial cancer, is a great challenge for endoscopists. Recently, the application of artificial intelligence (AI) using deep learning in the endoscopic field has made significant advancements in diagnosing gastrointestinal cancers. In the present study, we [...] Read more.

Diagnosis of early esophageal neoplasia, including dysplasia and superficial cancer, is a great challenge for endoscopists. Recently, the application of artificial intelligence (AI) using deep learning in the endoscopic field has made significant advancements in diagnosing gastrointestinal cancers. In the present study, we constructed a single-shot multibox detector using a convolutional neural network for diagnosing different histological grades of esophageal neoplasms and evaluated the diagnostic accuracy of this computer-aided system. A total of 936 endoscopic images were used as training images, and these images included 498 white-light imaging (WLI) and 438 narrow-band imaging (NBI) images. The esophageal neoplasms were divided into three classifications: squamous low-grade dysplasia, squamous high-grade dysplasia, and squamous cell carcinoma, based on pathological diagnosis. This AI system analyzed 264 test images in 10 s, and the sensitivity, specificity, and diagnostic accuracy of this system in detecting esophageal neoplasms were 96.2%, 70.4%, and 90.9%, respectively. The accuracy of this AI system in differentiating the histological grade of esophageal neoplasms was 92%. Our system showed better accuracy in diagnosing NBI (95%) than WLI (89%) images. Our results showed the great potential of AI systems in identifying esophageal neoplasms as well as differentiating histological grades. Full article

(This article belongs to the Special Issue Recent Research on Gastrointestinal Carcinoma)

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17 pages, 20777 KiB

Open AccessArticle

The Long Noncoding RNA LOC441461 (STX17-AS1) Modulates Colorectal Cancer Cell Growth and Motility

by Jui-Ho Wang, Tzung-Ju Lu, Mei-Lang Kung, Yi-Fang Yang, Chung-Yu Yeh, Ya-Ting Tu, Wei-Shone Chen and Kuo-Wang Tsai

Cancers 2020, 12(11), 3171; https://doi.org/10.3390/cancers12113171 - 28 Oct 2020

Cited by 13 | Viewed by 2817

Abstract

Colorectal carcinoma (CRC) is one of the most prevalent cancers worldwide and has a high mortality rate. Long noncoding RNAs (lncRNAs) have been noted to play critical roles in cell growth; cell apoptosis; and metastasis in CRC. This study determined that LOC441461 expression [...] Read more.

Colorectal carcinoma (CRC) is one of the most prevalent cancers worldwide and has a high mortality rate. Long noncoding RNAs (lncRNAs) have been noted to play critical roles in cell growth; cell apoptosis; and metastasis in CRC. This study determined that LOC441461 expression was significantly higher in CRC tissues than in adjacent normal mucosa. Pathway enrichment analysis of LOC441461-coexpressed genes revealed that LOC441461 was involved in biological functions related to cancer cell growth and motility. Knockdown of the LOC441461 expression significantly suppressed colon cancer cell growth by impairing cell cycle progression and inducing cell apoptosis. Furthermore, significantly higher LOC441461 expression was discovered in primary colon tumors and metastatic liver tumors than in the corresponding normal mucosa, and LOC441461 knockdown was noted to suppress colon cancer cell motility. Knockdown of LOC441461 expression suppressed the phosphorylation of MLC and LIMK1 through the inhibition of RhoA/ROCK signaling. Overall, LOC441461 was discovered to play an oncogenic role in CRC cell growth and motility through RhoA/ROCK signaling. Our findings provide new insights into the regulation of lncRNAs and their application in the treatment of colon cancer Full article

(This article belongs to the Special Issue Recent Research on Gastrointestinal Carcinoma)

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13 pages, 976 KiB

Open AccessArticle

Preoperative or Perioperative Docetaxel, Oxaliplatin, and Capecitabine (GASTRODOC Regimen) in Patients with Locally-Advanced Resectable Gastric Cancer: A Randomized Phase-II Trial

by Manlio Monti, Paolo Morgagni, Oriana Nanni, Massimo Framarini, Luca Saragoni, Daniele Marrelli, Franco Roviello, Roberto Petrioli, Uberto Fumagalli Romario, Lorenza Rimassa, Silvia Bozzarelli, Annibale Donini, Luigina Graziosi, Verena De Angelis, Giovanni De Manzoni, Maria Bencivenga, Valentina Mengardo, Emilio Parma, Carlo Milandri, Gianni Mura, Alessandra Signorini, Gianluca Baiocchi, Sarah Molfino, Giovanni Sgroi, Francesca Steccanella, Stefano Rausei, Ilaria Proserpio, Jacopo Viganò, Silvia Brugnatelli, Andrea Rinnovati, Stefano Santi, Giorgio Ercolani, Flavia Foca, Linda Valmorri, Dino Amadori and Giovanni Luca Frassineti Show full author list Hide full author list

Cancers 2020, 12(10), 2790; https://doi.org/10.3390/cancers12102790 - 29 Sep 2020

Cited by 15 | Viewed by 2600

Abstract

Docetaxel associated with oxaliplatin and 5-fluorouracil (FLOT) has been reported as the best perioperative treatment for gastric cancer. However, there is still some debate about the most appropriate number and timing of chemotherapy cycles. In this randomized multicenter phase II study, patients with [...] Read more.

Docetaxel associated with oxaliplatin and 5-fluorouracil (FLOT) has been reported as the best perioperative treatment for gastric cancer. However, there is still some debate about the most appropriate number and timing of chemotherapy cycles. In this randomized multicenter phase II study, patients with resectable gastric cancer were staged through laparoscopy and peritoneal lavage cytology, and randomly assigned (1:1) to either four cycles of neoadjuvant chemotherapy (arm A) or two preoperative + two postoperative cycles of docetaxel, oxaliplatin, and capecitabine (DOC) chemotherapy (arm B). The primary endpoint was to assess the percentage of patients receiving all the planned preoperative or perioperative chemotherapeutic cycles. Ninety-one patients were enrolled between September 2010 and August 2016. The treatment was well tolerated in both arms. Thirty-three (71.7%) and 24 (53.3%) patients completed the planned cycles in arms A and B, respectively (p = 0.066), reporting an odds ratio for early interruption of treatment of 0.45 (95% confidence interval (CI): 0.18–1.07). Resection was curative in 39 (88.6%) arm A patients and 35 (83.3%) arm B patients. Five-year progression-free survival (PFS) was 51.2% (95% CI: 34.2–65.8) in arm A and 40.3% (95% CI: 28.9–55.2) in arm B (p = 0.300). Five-year survival was 58.5% (95% CI: 41.3–72.2) and 53.9% (95% CI: 35.5–69.3) (p = 0.883) in arms A and B, respectively. The planned treatment was more frequently completed and was more active, albeit not significantly, in the neoadjuvant arm than in the perioperative group. Full article

(This article belongs to the Special Issue Recent Research on Gastrointestinal Carcinoma)

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13 pages, 4127 KiB

Open AccessArticle

Acute Radiation Colitis after Preoperative Short-Course Radiotherapy for Rectal Cancer: A Morphological, Immunohistochemical and Genetic Study

by Magda Zanelli, Alessia Ciarrocchi, Giovanni De Petris, Maurizio Zizzo, Massimo Costantini, Alessandra Bisagni, Federica Torricelli, Davide Nicoli, Dafne Ramundo, Stefano Ricci, Andrea Palicelli, Francesca Sanguedolce, Stefano Ascani, Carolina Castro Ruiz, Valerio Annessi, Raffaella Zamponi, Mara Bortesi, Veronica Martino, Marialisa Marchetti and Loredana De Marco

Cancers 2020, 12(9), 2571; https://doi.org/10.3390/cancers12092571 - 09 Sep 2020

Cited by 4 | Viewed by 3222

Abstract

Preoperative radiotherapy is a widely accepted treatment procedure in rectal cancer. Radiation-induced changes in the tumor are well described, whereas less attention has been given to the non-neoplastic mucosa. Our aim is to provide a detailed analysis of the morphological features present in [...] Read more.

Preoperative radiotherapy is a widely accepted treatment procedure in rectal cancer. Radiation-induced changes in the tumor are well described, whereas less attention has been given to the non-neoplastic mucosa. Our aim is to provide a detailed analysis of the morphological features present in non-neoplastic mucosa that pathologists need to be familiar with, in order to avoid misdiagnosis, when evaluating rectal cancer specimens of patients preoperatively treated with radiotherapy, especially with short-course regimen. We compared 2 groups of 95 rectal cancer patients treated preoperatively with either short-course (45 patients) or long-course radiotherapy (50 patients). Depending on the type of protocol, different histopathological features, in terms of inflammation, glandular abnormalities and endocrine differentiation were seen in the non-neoplastic mucosa within the irradiated volume. Of note, features mimicking dysplasia, such as crypt distortion, nuclear and cytoplasmic atypia of glandular epithelium, were identified only in the short-course group. DNA mutation analysis, using a panel of 56 genes frequently mutated in cancer, and p53 immunostaining were performed on both tumor and radiation-damaged mucosa in a subset of short course cases. Somatic mutations were identified only in tumors, supporting the concept that tissues with radiation-induced “dysplastic-like” features are not genetically transformed. Pathologists should be aware of the characteristic morphological changes induced by radiation. The presence of features simulating dysplasia in the group treated with short-course radiotherapy may lead to serious diagnostic mistakes, if erroneously interpreted. Next generation sequencing (NGS) analysis further validated the morphological concept that radiation-induced abnormalities do not represent pre-neoplastic lesions. Full article

(This article belongs to the Special Issue Recent Research on Gastrointestinal Carcinoma)

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14 pages, 853 KiB

Open AccessArticle

High-Throughput Sequencing of Gastric Cancer Patients: Unravelling Genetic Predispositions Towards an Early-Onset Subtype

by Julita Machlowska, Przemysław Kapusta, Jacek Baj, Folkert H. M. Morsink, Paweł Wołkow, Ryszard Maciejewski, G. Johan A. Offerhaus and Robert Sitarz

Cancers 2020, 12(7), 1981; https://doi.org/10.3390/cancers12071981 - 21 Jul 2020

Cited by 20 | Viewed by 3934

Abstract

Background: Gastric cancer is the fourth most common cause of cancer-related death. Currently, it is broadly accepted that the molecular complexity and heterogeneity of gastric cancer, both inter- and intra-tumor, display important barriers for finding specific biomarkers for the early detection and diagnosis [...] Read more.

Background: Gastric cancer is the fourth most common cause of cancer-related death. Currently, it is broadly accepted that the molecular complexity and heterogeneity of gastric cancer, both inter- and intra-tumor, display important barriers for finding specific biomarkers for the early detection and diagnosis of this malignancy. Early-onset gastric cancer is not as prevalent as conventional gastric carcinoma, but it is a preferable model for studying the genetic background, as young patients are less exposed to environmental factors, which influence cancer development. Aim: The main objective of this study was to reveal age-dependent genotypic characteristics of gastric cancer subtypes, as well as conduct mutation profiling for the most frequent alterations in gastric cancer development, using targeted next-generation sequencing technology. Patients and methods: The study group included 53 patients, consisting of 18 patients with conventional gastric cancer and 35 with an early-onset subtype. The DNA of all index cases was used for next-generation sequencing, employing a panel of 94 genes and 284 single nucleotide polymorphisms (SNPs) (TruSight Cancer Panel, Illumina), which is characteristic for common and rare types of cancer. Results: From among the 53 samples processed for sequencing, we were able to identify seven candidate genes (STK11, RET, FANCM, SLX4, WRN, MEN1, and KIT) and nine variants among them: one splice_acceptor, four synonymous, and four missense variants. These were selected for the age-dependent differentiation of gastric cancer subtypes. We found four variants with C-Score ≥ 10, as 10% of the most deleterious substitutions: rs1800862 (RET), rs10138997 (FANCM), rs2230009 (WRN), and rs2959656 (MEN1). We identified 36 different variants, among 24 different genes, which were the most frequent genetic alterations among study subjects. We found 16 different variants among the genes that were present in 100% of the total cohort: SDHB (rs2746462), ALK (rs1670283), XPC (rs2958057), RECQL4 (rs4925828; rs11342077, rs398010167; rs2721190), DDB2 (rs326212), MEN1 (rs540012), AIP (rs4930199), ATM (rs659243), HNF1A (rs1169305), BRCA2 (rs206075; rs169547), ERCC5 (rs9514066; rs9514067), and FANCI (rs7183618). Conclusions: The technology of next-generation sequencing is a useful tool for studying the development and progression of gastric carcinoma in a high-throughput way. Our study revealed that early-onset gastric cancer has a different mutation frequency profile in certain genes compared to conventional subtype. Full article

(This article belongs to the Special Issue Recent Research on Gastrointestinal Carcinoma)

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16 pages, 1833 KiB

Open AccessArticle

From CENTRAL to SENTRAL (SErum aNgiogenesis cenTRAL): Circulating Predictive Biomarkers to Anti-VEGFR Therapy

by Riccardo Giampieri, Pina Ziranu, Bruno Daniele, Antonio Zizzi, Daris Ferrari, Sara Lonardi, Alberto Zaniboni, Luigi Cavanna, Gerardo Rosati, Mariaelena Casagrande, Nicoletta Pella, Laura Demurtas, Maria Giulia Zampino, Pietro Sozzi, Valeria Pusceddu, Domenico Germano, Eleonora Lai, Vittorina Zagonel, Carla Codecà, Michela Libertini, Marco Puzzoni, Roberto Labianca, Stefano Cascinu and Mario Scartozzi Show full author list Hide full author list

Cancers 2020, 12(5), 1330; https://doi.org/10.3390/cancers12051330 - 22 May 2020

Cited by 8 | Viewed by 3047

Abstract

Background: In the last decade, a series of analyses failed to identify predictive biomarkers of resistance/susceptibility for anti-angiogenic drugs in metastatic colorectal cancer (mCRC). We conducted an exploratory preplanned analysis of serum pro-angiogenic factors (SErum aNgiogenesis-cenTRAL) in 72 mCRC patients enrolled in the [...] Read more.

Background: In the last decade, a series of analyses failed to identify predictive biomarkers of resistance/susceptibility for anti-angiogenic drugs in metastatic colorectal cancer (mCRC). We conducted an exploratory preplanned analysis of serum pro-angiogenic factors (SErum aNgiogenesis-cenTRAL) in 72 mCRC patients enrolled in the phase II CENTRAL (ColorEctalavastiNTRiAlLdh) trial, with the aim to identify potential predictive factors for sensitivity/resistance to first line folinic acid-fluorouracil-irinotecan regimen (FOLFIRI) plus bevacizumab. Methods: First-line FOLFIRI/bevacizumab patients were prospectively assessed for the following circulating pro-angiogenic factors, evaluated with ELISA (enzyme-linked immunosorbent assay)-based technique at baseline and at every cycle: Vascular endothelial growth factor A (VEGF-A), hepatocyte growth factor (HGF), stromal derived factor-1 (SDF-1), placental derived growth factor (PlGF), fibroblast growth factor-2 (FGF-2), monocyte chemotactic protein-3 (MCP-3), interleukin-8 (IL-8). Results: Changes in circulating FGF-2 levels among different blood samples seemed to correlate with clinical outcome. Patients who experienced an increase in FGF-2 levels at the second cycle of chemotherapy compared to baseline, had a median Progression Free Survival (mPFS) of 12.85 vs. 7.57 months (Hazard Ratio—HR: 0.73, 95% Confidence Interval—CI: 0.43-1.27, p = 0.23). Similar results were seen when comparing FGF-2 concentrations between baseline and eight-week time point (mPFS 12.98 vs. 8.00 months, HR: 0.78, 95% CI: 0.46–1.33, p = 0.35). Conclusions: Our pre-planned, prospective analysis suggests that circulating FGF-2 levels’ early increase could be used as a marker to identify patients who are more likely to gain benefit from FOLFIRI/bevacizumab first-line therapy. Full article

(This article belongs to the Special Issue Recent Research on Gastrointestinal Carcinoma)

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12 pages, 995 KiB

Open AccessArticle

mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated with Everolimus

by Fabio Gelsomino, Andrea Casadei-Gardini, Francesco Caputo, Giulio Rossi, Federica Bertolini, Tiziana Petrachi, Andrea Spallanzani, Elisa Pettorelli, Shaniko Kaleci and Gabriele Luppi

Cancers 2020, 12(5), 1201; https://doi.org/10.3390/cancers12051201 - 10 May 2020

Cited by 5 | Viewed by 2427

Abstract

Background. Everolimus (Eve), which is a mammalian target of Rapamicin (mTOR) inhibitor, is part of the therapeutic armamentarium of neuroendocrine tumors (NETs). Currently, there are no validated biomarkers predicting Eve efficacy in NETs. In this study, we explore whether the expression of phosphorilated [...] Read more.

Background. Everolimus (Eve), which is a mammalian target of Rapamicin (mTOR) inhibitor, is part of the therapeutic armamentarium of neuroendocrine tumors (NETs). Currently, there are no validated biomarkers predicting Eve efficacy in NETs. In this study, we explore whether the expression of phosphorilated (p)-mTOR and p70S6-kinase (S6K), a downstream effector of mTOR, correlates with the outcome of patients with NET that were treated with Eve. Methods. Tissue specimens that were derived from NETs treated with Eve at our Institution were examined for the expression levels of p-mTOR and p-S6K by immunohistochemistry. Response rate (RR), progression-free survival (PFS), and overall survival (OS) were analyzed in two groups: p-mTOR/p-S6K positive (group 1) and p-mTOR/p-S6K negative (group 2). Univariate and multivariate Cox regression analysis were performed. Results. Twenty-four patients with advanced NETs that were treated with Eve were included in the analysis. Eight out 24 (33.3%) patients were both p-mTOR and p-S6K positive. A better median PFS and OS in group 1 (18.2 and 39.9 months) as compared to group 2 (13 and 32.4 months) was depicted, with a toxicity profile that was comparable with data literature. Conclusions. Our study suggests that the activation of mTOR pathway can predict better outcomes in patients with NET treated with Eve. However, these results warrant further confirmation in a prospective setting. Full article

(This article belongs to the Special Issue Recent Research on Gastrointestinal Carcinoma)

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12 pages, 1771 KiB

Open AccessArticle

Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer

by Eizaburou Hideura, Yutaka Suehiro, Jun Nishikawa, Takuya Shuto, Hiroyuki Fujimura, Shunsuke Ito, Atsushi Goto, Kouichi Hamabe, Issei Saeki, Takeshi Okamoto, Shingo Higaki, Ikuei Fujii, Chieko Suzuki, Tomomi Hoshida, Toshihiko Matsumoto, Taro Takami, Isao Sakaida and Takahiro Yamasaki

Cancers 2020, 12(4), 789; https://doi.org/10.3390/cancers12040789 - 26 Mar 2020

Cited by 18 | Viewed by 3212

Abstract

The main modalities for gastric cancer screening are limited to upper gastrointestinal endoscopy and contrast radiography. The former is invasive, and the latter has high false-negative rates. Thus, alternative diagnostic strategies are required. One solution may be a liquid biopsy. Methylated RUNX3 is [...] Read more.

The main modalities for gastric cancer screening are limited to upper gastrointestinal endoscopy and contrast radiography. The former is invasive, and the latter has high false-negative rates. Thus, alternative diagnostic strategies are required. One solution may be a liquid biopsy. Methylated RUNX3 is a well-known biomarker of gastric cancer but it is very difficult to detect with conventional bisulfite-based methylation assays when only a small amount of serum is available. We developed the combined restriction digital PCR (CORD) assay, a new methylation assay allowing for the counting of as little as one copy of a methylated gene in a small sample of DNA without necessitating DNA bisulfite treatment. We evaluated the sensitivity and specificity of the serum DNA testing of methylated RUNX3 by the CORD assay for the detection of early gastric cancer using 50 patients with early gastric cancer and 61 control individuals. The CORD assay had a sensitivity of 50.0% and a specificity of 80.3% for early gastric cancer. Methylated RUNX3 copies were significantly associated with tumor size, massive submucosal invasion, and lymph-vascular invasion. After the treatment, the median number of methylated RUNX3 copies was significantly decreased. The CORD assay may provide an alternative screening strategy to detect even early-stage gastric cancer. Full article

(This article belongs to the Special Issue Recent Research on Gastrointestinal Carcinoma)

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14 pages, 1798 KiB

Open AccessArticle

¹H-NMR Based Serum Metabolomics Highlights Different Specific Biomarkers between Early and Advanced Hepatocellular Carcinoma Stages

by Andrea Casadei-Gardini, Laura Del Coco, Giorgia Marisi, Fabio Conti, Giulia Rovesti, Paola Ulivi, Matteo Canale, Giovanni Luca Frassineti, Francesco Giuseppe Foschi, Serena Longo, Francesco Paolo Fanizzi and Anna Maria Giudetti

Cancers 2020, 12(1), 241; https://doi.org/10.3390/cancers12010241 - 18 Jan 2020

Cited by 40 | Viewed by 5485

Abstract

The application of non-targeted serum metabolomics profiling represents a noninvasive tool to identify new clinical biomarkers and to provide early diagnostic differentiation, and insight into the pathological mechanisms underlying hepatocellular carcinoma (HCC) progression. In this study, we used proton Nuclear Magnetic Resonance ( [...] Read more.

The application of non-targeted serum metabolomics profiling represents a noninvasive tool to identify new clinical biomarkers and to provide early diagnostic differentiation, and insight into the pathological mechanisms underlying hepatocellular carcinoma (HCC) progression. In this study, we used proton Nuclear Magnetic Resonance (¹H-NMR) Spectroscopy and multivariate data analysis to profile the serum metabolome of 64 HCC patients, in early (n = 28) and advanced (n = 36) disease stages. We found that ¹H-NMR metabolomics profiling could discriminate early from advanced HCC patients with a cross-validated accuracy close to 100%. Orthogonal partial least squares discriminant analysis (OPLS-DA) showed significant changes in serum glucose, lactate, lipids and some amino acids, such as alanine, glutamine, 1-methylhistidine, lysine and valine levels between advanced and early HCC patients. Moreover, in early HCC patients, Kaplan–Meier analysis highlighted the serum tyrosine level as a predictor for overall survival (OS). Overall, our analysis identified a set of metabolites with possible clinical and biological implication in HCC pathophysiology. Full article

(This article belongs to the Special Issue Recent Research on Gastrointestinal Carcinoma)

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Review

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14 pages, 1294 KiB

Open AccessReview

Complementary Use of Carbohydrate Antigens Lewis a, Lewis b, and Sialyl-Lewis a (CA19.9 Epitope) in Gastrointestinal Cancers: Biological Rationale towards a Personalized Clinical Application

by Rossella Indellicato, Aida Zulueta, Anna Caretti and Marco Trinchera

Cancers 2020, 12(6), 1509; https://doi.org/10.3390/cancers12061509 - 09 Jun 2020

Cited by 16 | Viewed by 4061

Abstract

Carbohydrate antigen 19.9 (CA19.9) is used as a tumor marker for clinical and research purposes assuming that it is abundantly produced by gastrointestinal cancer cells due to a cancer-associated aberrant glycosylation favoring its synthesis. Recent data has instead suggested a different picture, where [...] Read more.

Carbohydrate antigen 19.9 (CA19.9) is used as a tumor marker for clinical and research purposes assuming that it is abundantly produced by gastrointestinal cancer cells due to a cancer-associated aberrant glycosylation favoring its synthesis. Recent data has instead suggested a different picture, where immunodetection on tissue sections matches biochemical and molecular data. In addition to CA19.9, structurally related carbohydrate antigens Lewis a and Lewis b are, in fact, undetectable in colon cancer, due to the down-regulation of a galactosyltransferase necessary for their synthesis. In the pancreas, no differential expression of CA19.9 or cognate glycosyltransferases occurs in cancer. Ductal cells only express such Lewis antigens in a pattern affected by the relative levels of each glycosyltransferase, which are genetically and epigenetically determined. The elevation of circulating antigens seems to depend on the obstruction of neoplastic ducts and loss of polarity occurring in malignant ductal cells. Circulating Lewis a and Lewis b are indeed promising candidates for monitoring pancreatic cancer patients that are negative for CA19.9, but not for improving the low diagnostic performance of such an antigen. Insufficient biological data are available for gastric and bile duct cancer. Studying each patient in a personalized manner determining all Lewis antigens in the surgical specimens and in the blood, together with the status of the tissue-specific glycosylation machinery, promises fruitful advances in translational research and clinical practice. Full article

(This article belongs to the Special Issue Recent Research on Gastrointestinal Carcinoma)

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33 pages, 851 KiB

Open AccessReview

Molecular-Biology-Driven Treatment for Metastatic Colorectal Cancer

by Eleonora Lai, Nicole Liscia, Clelia Donisi, Stefano Mariani, Simona Tolu, Andrea Pretta, Mara Persano, Giovanna Pinna, Francesca Balconi, Annagrazia Pireddu, Valentino Impera, Marco Dubois, Marco Migliari, Dario Spanu, Giorgio Saba, Silvia Camera, Francesca Musio, Pina Ziranu, Marco Puzzoni, Laura Demurtas, Valeria Pusceddu, Manuela Dettori, Elena Massa, Francesco Atzori, Mariele Dessì, Giorgio Astara, Clelia Madeddu and Mario Scartozzi Show full author list Hide full author list

Cancers 2020, 12(5), 1214; https://doi.org/10.3390/cancers12051214 - 13 May 2020

Cited by 24 | Viewed by 6510

Abstract

Background: Metastatic CRC (mCRC) is a molecular heterogeneous disease. The aim of this review is to give an overview of molecular-driven treatment of mCRC patients. Methods: A review of clinical trials, retrospective studies and case reports was performed regarding molecular biomarkers with therapeutic [...] Read more.

Background: Metastatic CRC (mCRC) is a molecular heterogeneous disease. The aim of this review is to give an overview of molecular-driven treatment of mCRC patients. Methods: A review of clinical trials, retrospective studies and case reports was performed regarding molecular biomarkers with therapeutic implications. Results: RAS wild-type status was confirmed as being crucial for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies and for rechallenge strategy. Antiangiogenic therapies improve survival in first- and second-line settings, irrespective of RAS status, while tyrosine kinase inhibitors (TKIs) remain promising in refractory mCRC. Promising results emerged from anti-HER2 drugs trials in HER2-positive mCRC. Target inhibitors were successful for BRAF^V600E mutant mCRC patients, while immunotherapy was successful for microsatellite instability-high/defective mismatch repair (MSI-H/dMMR) or DNA polymerase epsilon catalytic subunit (POLE-1) mutant patients. Data are still lacking on NTRK, RET, MGMT, and TGF-β, which require further research. Conclusion: Several molecular biomarkers have been identified for the tailored treatment of mCRC patients and multiple efforts are currently ongoing to increase the therapeutic options. In the era of precision medicine, molecular-biology-driven treatment is the key to impro patient selection and patient outcomes. Further research and large phase III trials are required to ameliorate the therapeutic management of these patients. Full article

(This article belongs to the Special Issue Recent Research on Gastrointestinal Carcinoma)

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