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Cancers
Special Issues
Precision Medicine in Gastrointestinal Oncology
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Precision Medicine in Gastrointestinal Oncology

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (1 March 2022) | Viewed by 19107

Special Issue Editor

Dr. Maen Abdelrahim

E-Mail Website
Guest Editor
1. Section of Gastrointestinal Oncology-Houston Methodist Cancer Center and Institute of Academic Medicine, 6445 Fannin, OPC-24, Houston, TX 77030, USA
2. Cockrell Center for Advanced Therapeutics (CCAT)—Phase I Program, Houston Methodist Research Institute, Houston, TX 77030, USA
3. Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
Interests: pancreatic cancer; liver cancer; cholangiocarcinoma; biliary cancer; transplant oncology; phase I drugs; targeted therapy; drug discovery; immunotherapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Precision medicine and targeted therapy have revolutionized the treatment of various cancers in the past decade. Precision medicine is a therapeutic approach designed to treat individual patients with the most appropriate treatment regimen based on the patients’ genetic and molecular profiles by using next-generation sequencing (NGS) to analyze the genes of their cancer cells. Using this approach, we can detect cancer-specific driver gene mutations for which molecular targeted drugs can be designed to specifically and effectively target such actionable gene mutation for a better outcome and minimal toxicity. Given our knowledge and the increased accessibility of affordable tumor genome sequencing technologies, targeted and immune-based cancer therapeutics have emerged as desirable treatment options not only by oncologists but also by cancer patients.  

With the increasing incidence and mortality of gastrointestinal (GI) cancers and the limited availability of successful therapy, there is an unmet need for a new approach to treat GI malignancies beyond the classical chemotherapy. The development of biomarkers as well as targeted therapies for GI cancer has recently been investigated and applied. Our knowledge of GI cancer molecular profile and biomarkers like Ras, BRAF, HER2, PDL-1, and others has led to the development and utilization of targeted and immuno-based therapies, and hence this Special Issue “Precision Medicine in Gastrointestinal Oncology".

In this Special Issue, we would like to highlight the advancement of precision medicine in GI cancer to inform oncologists and readers about the current availability and use of targeted therapies in upper and lower GI cancers. Our goal is to describe the biomarker-based rationale behind GI cancer classifications in addition to publishing recent advances in GI cancer targeted therapy that include basic, translational, and prospective and retrospective clinical discoveries from esophageal, gastric, colorectal, pancreatic, as well as hepatobiliary cancers.

In this Special Issue we would also like to emphasize emerging targeted strategies that include targeting IDH, FGFR, EGFR, VEGFR, claudin 18.2, HER2, MET, PD-1/PD-L1, PD-L2, BRCA/PARP, and PIK3CA/Akt pathways, as well as other newly discovered and applied targets and immuno-modulatory pathways in GI malignancies. We encourage you to submit your original research articles, however, review articles and case series with clear educational points and analysis are welcomed and will be equally considered. 

In this Special Issue we will also accept manuscripts that highlight and descript the current progress in circulating tumor cells, circulating tumor DNA, stool DNA, microRNAs, and the exosome as diagnostic, monitoring, and predictive markers in gastrointestinal cancer.

Dr. Maen Abdelrahim
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • targeted therapy in GI cancers
  • novel therapeutic targets in GI cancers
  • actionable mutations in GI cancers
  • targeted therapy in combination with chemotherapy
  • targeted therapy in combination with immunotherapy
  • resistant mechanisms of GI targeted therapy
  • toxicity of GI targeted therapy
  • predictive biomarkers in GI cancers
  • diagnostic and monitoring markers in GI cancers

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Published Papers (4 papers)

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24 pages, 5669 KiB  
Review
Utility of Cell-Free DNA Detection in Transplant Oncology
by Tejaswini Reddy, Abdullah Esmail, Jenny C. Chang, Rafik Mark Ghobrial and Maen Abdelrahim
Cancers 2022, 14(3), 743; https://doi.org/10.3390/cancers14030743 - 31 Jan 2022
Cited by 13 | Viewed by 5210
Abstract
Transplant oncology is an emerging field in cancer treatment that applies transplant medicine, surgery, and oncology to improve cancer patient survival and quality of life. A critical concept that must be addressed to ensure the successful application of transplant oncology to patient care [...] Read more.
Transplant oncology is an emerging field in cancer treatment that applies transplant medicine, surgery, and oncology to improve cancer patient survival and quality of life. A critical concept that must be addressed to ensure the successful application of transplant oncology to patient care is efficient monitoring of tumor burden pre-and post-transplant and transplant rejection. Cell-free DNA (cfDNA) detection has emerged as a vital tool in revolutionizing the management of cancer patients who undergo organ transplantation. The advances in cfDNA technology have provided options to perform a pre-transplant evaluation of minimal residual disease (MRD) and post-transplant evaluation of cancer recurrence and transplant rejection. This review aims to provide a comprehensive overview of the history and emergence of cfDNA technology, its applications to specifically monitor tumor burden at pre-and post-transplant stages, and evaluate transplant rejection. Full article
(This article belongs to the Special Issue Precision Medicine in Gastrointestinal Oncology)
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13 pages, 1490 KiB  
Review
Transplant Oncology: An Evolving Field in Cancer Care
by Maen Abdelrahim, Abdullah Esmail, Ala Abudayyeh, Naoka Murakami, Ashish Saharia, Robert McMillan, David Victor, Sudha Kodali, Akshay Shetty, Joy V. Nolte Fong, Linda W. Moore, Kirk Heyne, A. Osama Gaber and Rafik Mark Ghobrial
Cancers 2021, 13(19), 4911; https://doi.org/10.3390/cancers13194911 - 29 Sep 2021
Cited by 39 | Viewed by 5320
Abstract
Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The application of oncology, transplant medicine, and surgery to improve patients’ survival and quality of life is the core of transplant oncology. Hepatobiliary malignancies have been treated by liver [...] Read more.
Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The application of oncology, transplant medicine, and surgery to improve patients’ survival and quality of life is the core of transplant oncology. Hepatobiliary malignancies have been treated by liver transplantation (LT) with significant improved outcome. In addition, as the liver is the most common site of metastasis for colorectal cancer (CRC), patients with CRC who have stable unresectable liver metastases are good candidates for LT, and initial studies have shown improved survival compared to palliative systemic therapy. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years in a stepwise manner; however, they have only been shown to improve patient survival in the setting of limited systemic therapy options. This review illustrates the concept and history of transplant oncology as an evolving field for the management of hepatocellular carcinoma, intrahepatic biliary cancer, and liver-only metastasis of non-hepatobiliary carcinoma. The utility of immunotherapy in the transplant setting is discussed as well as the feasibility of using circulating tumor DNA for surveillance post-transplantation. Full article
(This article belongs to the Special Issue Precision Medicine in Gastrointestinal Oncology)
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16 pages, 1270 KiB  
Review
Playing on the Dark Side: SMYD3 Acts as a Cancer Genome Keeper in Gastrointestinal Malignancies
by Paola Sanese, Candida Fasano and Cristiano Simone
Cancers 2021, 13(17), 4427; https://doi.org/10.3390/cancers13174427 - 2 Sep 2021
Cited by 9 | Viewed by 3613
Abstract
The SMYD3 methyltransferase has been found overexpressed in several types of cancers of the gastrointestinal (GI) tract. While high levels of SMYD3 have been positively correlated with cancer progression in cellular and advanced mice models, suggesting it as a potential risk and prognosis [...] Read more.
The SMYD3 methyltransferase has been found overexpressed in several types of cancers of the gastrointestinal (GI) tract. While high levels of SMYD3 have been positively correlated with cancer progression in cellular and advanced mice models, suggesting it as a potential risk and prognosis factor, its activity seems dispensable for autonomous in vitro cancer cell proliferation. Here, we present an in-depth analysis of SMYD3 functional role in the regulation of GI cancer progression. We first describe the oncogenic activity of SMYD3 as a transcriptional activator of genes involved in tumorigenesis, cancer development and transformation and as a co-regulator of key cancer-related pathways. Then, we dissect its role in orchestrating cell cycle regulation and DNA damage response (DDR) to genotoxic stress by promoting homologous recombination (HR) repair, thereby sustaining cancer cell genomic stability and tumor progression. Based on this evidence and on the involvement of PARP1 in other DDR mechanisms, we also outline a synthetic lethality approach consisting of the combined use of SMYD3 and PARP inhibitors, which recently showed promising therapeutic potential in HR-proficient GI tumors expressing high levels of SMYD3. Overall, these findings identify SMYD3 as a promising target for drug discovery. Full article
(This article belongs to the Special Issue Precision Medicine in Gastrointestinal Oncology)
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Other

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13 pages, 1318 KiB  
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Transarterial Chemoembolization (TACE) Plus Sorafenib Compared to TACE Alone in Transplant Recipients with Hepatocellular Carcinoma: An Institution Experience
by Maen Abdelrahim, David Victor, Abdullah Esmail, Sudha Kodali, Edward A. Graviss, Duc T. Nguyen, Linda W. Moore, Ashish Saharia, Robert McMillan, Joy N. Fong, Ahmed Uosef, Mahmoud Elshawwaf, Kirk Heyne and Rafik M. Ghobrial
Cancers 2022, 14(3), 650; https://doi.org/10.3390/cancers14030650 - 27 Jan 2022
Cited by 25 | Viewed by 3500
Abstract
Background: Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third most common cause of cancer-related mortality worldwide. Transarterial chemoembolization has shown survival benefits in patients with early to intermediate-stage HCC, becoming the standard of care and recommended treatment modality by [...] Read more.
Background: Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third most common cause of cancer-related mortality worldwide. Transarterial chemoembolization has shown survival benefits in patients with early to intermediate-stage HCC, becoming the standard of care and recommended treatment modality by most clinical practice guidelines. The most recent trials of the TACE plus sorafenib combined therapy in patients with unresectable HCC have yielded inconsistent outcomes. The purpose of this study was to compare the outcomes of HCC patients treated with the TACE sorafenib combination as opposed to TACE monotherapy. Methods: This retrospective study included all patients with unresectable HCC who underwent liver transplantation and were treated by either TACE alone or TACE plus sorafenib between July 2008–December 2019. Demographic and clinical data as well as HCC recurrence post-liver transplant (LT) were reported as frequencies and proportions for categorical variables and as the median and interquartile range (IQR) or mean. Chi-square or Fisher’s exact tests were performed for categorical variables and the Kruskal-Wallis test or unpaired test was performed for continuous variables. Kaplan-Meier curves present overall patient survival and HCC-free survival. Results: A total of 128 patients received LT, with a median (IQR) age of 61.4 (57.0, 66.3) years; most were males (77%). Within the TACE-only group, 79 (77%) patients met the Milan criteria and 24 (23%) were beyond the Milan criteria, while the TACE plus sorafenib group had a higher proportion of patients beyond the Milan criteria: 16 (64%) vs. 9 (36%); p = 0.01. The five-year disease-free survival (DFS) between the treatment groups approached significance, with 100% DFS in the TACE plus sorafenib group vs. 67.2% in the TACE-alone group, p = 0.07. Five-year patient survival was 77.8% in the TACE plus sorafenib group compared to 61.5% in the TACE-alone group (p = 0.51). However, in patients who met the beyond Milan criteria, those who received TACE alone had a lower average amount of (percent) tumor necrosis on explant pathology (43.8% ± 32%) compared to patients who received TACE plus sorafenib (69.6% ± 32.8%, p = 0.03). Conclusion: This study identified that using TACE plus sorafenib is generally well-tolerated and demonstrated improved overall survival compared to TACE only in transplant recipients with unresectable HCC. A multi-center and prospective randomized controlled trial is needed to substantiate these findings. Full article
(This article belongs to the Special Issue Precision Medicine in Gastrointestinal Oncology)
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