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Cancers
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Chemotherapy for Colorectal Cancer
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Chemotherapy for Colorectal Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (1 June 2023) | Viewed by 10300

Special Issue Editor

Dr. Atsuo Takashima

E-Mail Website
Guest Editor
Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
Interests: colon cancer; clinical trial; targeted therapy; immunotherapy

Special Issue Information

Dear Colleagues,

In recent years, target therapy has developed in colorectal cancer. Over the years, there have been many challenges, such as the proper positioning of molecular-targeted drugs, postoperative adjuvant chemotherapy, and chemotherapy for elderly.

In this Special Issue, we wish to collect original research and review articles which address all innovations dedicated to treatments for elderly patients, adjuvant treatment, immune checkpoint inhibitors, and targeted therapies.

We hope that this Special Issue will contribute to furthering understanding on the recent advancements and future perspectives regarding chemotherapy for colorectal cancer.

Dr. Atsuo Takashima
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 short 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

  • adjuvant chemotherapy
  • FOLFOXIRI-based chemotherapy
  • anti-VEGF treatment (second line treatment)
  • salvage-line treatment (TAS102, Regorafenib, Fruquintinib, TAS102+BV)
  • targeted therapy (BRAF V600E mt, HER2 overexpression, KRAS G12C mt)
  • tumor sidedness
  • elderly patients

Published Papers (5 papers)

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Research

Jump to: Review

17 pages, 1500 KiB  
Article
The Impact of Sidedness on the Efficacy of Anti-EGFR-Based First-Line Chemotherapy in Advanced Colorectal Cancer Patients in Real-Life Setting—A Nation-Wide Retrospective Analysis (RACER)
by Paweł Michał Potocki, Rafał Wiśniowski, Dominik Haus, Zbyszko Chowaniec, Maciej Kozaczka, Magdalena Kustra, Marzenna Samborska-Plewicka, Marcin Szweda, Danuta Starzyczny-Słota, Magdalena Michalik, Grzegorz Słomian, Aneta Lebiedzińska, Natalia Jonak-Olczyk, Natalia Łaszewska-Kraińska, Krzysztof Adamowicz, Piotr Kolenda, Anna Drosik-Kwaśniewska, Marek Szwiec, Robert Dziura, Justyna Czech, Maria Dąbrowska, Ewa Nowakowska-Zajdel, Ewa Klank-Sokołowska, Kamil Konopka, Łukasz Kwinta, Jolanta Dobrzańska and Piotr J. Wysockiadd Show full author list remove Hide full author list
Cancers 2023, 15(17), 4361; https://doi.org/10.3390/cancers15174361 - 1 Sep 2023
Viewed by 1263
Abstract
Anti-EGFR antibodies combined with chemotherapy doublets are a cornerstone of the upfront treatment of colorectal cancer. RAS and BRAF mutations are established negative predictive factors for such therapy. The primary tumour located in the proximal colon has recently emerged as another negative predictive [...] Read more.
Anti-EGFR antibodies combined with chemotherapy doublets are a cornerstone of the upfront treatment of colorectal cancer. RAS and BRAF mutations are established negative predictive factors for such therapy. The primary tumour located in the proximal colon has recently emerged as another negative predictive factor. We have conducted a retrospective multicentre study to collect data on real-world population characteristics, practice patterns, and outcomes in patients with metastatic colorectal cancer treated in a first-line setting with either cetuximab or panitumumab in combination with either FOLFOX or FOLFIRI chemotherapy. The presented analysis focuses on the impact of the primary tumour location. 126 of 842 patients analysed (15.0%) had proximal primary. It was associated with a lower BMI at diagnosis, mucinous histology, and peritoneal metastases. It was also associated with inferior treatment outcomes in terms of response ratio: 59.4% vs. 74.22% (odds ratio [OR] 0.51, 95% CI 0.33–0.78, p = 0.010), and median depth of response: −36.7% vs. −50.0% (p = 0.038). There was only a borderline non-significant trend for inferior PFS in patients with proximal tumours. OS data was incomplete. The presented analysis confirms the negative impact of tumour sidedness on the efficacy of an upfront anti-EGFR-chemotherapy combination and provides valuable data on real-world population characteristics. Full article
(This article belongs to the Special Issue Chemotherapy for Colorectal Cancer)
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20 pages, 3648 KiB  
Article
Increasing Dosage of Leucovorin Results in Pharmacokinetic and Gene Expression Differences When Administered as Two-Hour Infusion or Bolus Injection to Patients with Colon Cancer
by Helena Taflin, Elisabeth Odin, Göran Carlsson, Bengt Gustavsson, Yvonne Wettergren and Elinor Bexe Lindskog
Cancers 2023, 15(1), 258; https://doi.org/10.3390/cancers15010258 - 30 Dec 2022
Viewed by 2348
Abstract
The combination of 5-fluorouracil (5-FU) and leucovorin (LV) forms the chemotherapy backbone for patients with colorectal cancer. However, the LV administration is often standardized and not based on robust scientific data. To address these issues, a randomized pharmacokinetics study was performed in patients [...] Read more.
The combination of 5-fluorouracil (5-FU) and leucovorin (LV) forms the chemotherapy backbone for patients with colorectal cancer. However, the LV administration is often standardized and not based on robust scientific data. To address these issues, a randomized pharmacokinetics study was performed in patients with colon cancer. Thirty patients were enrolled, receiving 60, 200 or 500 mg/m2 LV as a single two-hour infusion. Blood, tumor, mucosa, and resection margin biopsies were collected. Folate concentrations were analyzed with LC-MS/MS and gene expression with qPCR. Data from a previous study where patients received LV as bolus injections were used as comparison. Saturation of methylenetetrahydrofolate (MeTHF) and tetrahydrofolate (THF) levels was seen after two-hour infusion and polyglutamated MeTHF + THF levels in tumors decreased with increasing LV dosage. The decrease was associated with decreased FPGS and increased GGH expression, which was not observed after LV bolus injection. In the bolus group, results indicate activation of a metabolic switch possibly promoting TYMS inhibition in response to 5-FU. Different metabolic mechanisms appear to be induced when LV is administered as infusion and bolus injection. Since maximal inhibition of TYMS by the 5-FU metabolite 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP) requires excess polyglutamated MeTHF, the results point in favor of the bolus regimen. Full article
(This article belongs to the Special Issue Chemotherapy for Colorectal Cancer)
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Review

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17 pages, 321 KiB  
Review
Current Status of Angiogenesis Inhibitors as Second-Line Treatment for Unresectable Colorectal Cancer
by Satoshi Otsu and Shuichi Hironaka
Cancers 2023, 15(18), 4564; https://doi.org/10.3390/cancers15184564 - 14 Sep 2023
Cited by 2 | Viewed by 1064
Abstract
Colorectal cancer is the third most common disease and the second most common cause of death around the world. The drug for second-line treatment depends on the drugs used in first-line treatment and the biomarker status. As biomarkers, the RAS gene, BRAF gene, [...] Read more.
Colorectal cancer is the third most common disease and the second most common cause of death around the world. The drug for second-line treatment depends on the drugs used in first-line treatment and the biomarker status. As biomarkers, the RAS gene, BRAF gene, and dMMR/MSI-H, TMB-H, and HER2 statuses have been established in clinical practice, and the corresponding molecularly targeted therapeutic agents are selected based on the biomarker status. Given the frequency of biomarkers, it is assumed that when patients move on to second-line treatment, an angiogenesis inhibitor is selected in many cases. For second-line treatment, three angiogenesis inhibitors, bevacizumab (BEV), ramucirumab (RAM), and aflibercept (AFL), are available, and one of them is combined with cytotoxic agents. These three angiogenesis inhibitors are known to inhibit angiogenesis through different mechanisms of action. Although no useful biomarkers have been established for the selection of angiogenesis inhibitors, previous biomarker studies have suggested that angiogenesis-related factors such as VEGF-A and VEGF-D might be predictors of the therapeutic efficacy of angiogenesis inhibitors. These biomarkers are measured as protein levels in plasma and are considered to be promising biomarkers. We consider that the rationale for selecting among these three angiogenesis inhibitors should be clarified to benefit patients. Full article
(This article belongs to the Special Issue Chemotherapy for Colorectal Cancer)
20 pages, 836 KiB  
Review
Circulating Tumor DNA: The Dawn of a New Era in the Optimization of Chemotherapeutic Strategies for Metastatic Colo-Rectal Cancer Focusing on RAS Mutation
by Shohei Udagawa, Akira Ooki, Eiji Shinozaki, Koshiro Fukuda, Kensei Yamaguchi and Hiroki Osumi
Cancers 2023, 15(5), 1473; https://doi.org/10.3390/cancers15051473 - 25 Feb 2023
Cited by 2 | Viewed by 2085
Abstract
Genotyping of tumor tissues to assess RAS and BRAF V600E mutations enables us to select optimal molecularly targeted therapies when considering treatment strategies for patients with metastatic colorectal cancer. Tissue-based genetic testing is limited by the difficulty of performing repeated tests, due to [...] Read more.
Genotyping of tumor tissues to assess RAS and BRAF V600E mutations enables us to select optimal molecularly targeted therapies when considering treatment strategies for patients with metastatic colorectal cancer. Tissue-based genetic testing is limited by the difficulty of performing repeated tests, due to the invasive nature of tissue biopsy, and by tumor heterogeneity, which can limit the usefulness of the information it yields. Liquid biopsy, represented by circulating tumor DNA (ctDNA), has attracted attention as a novel method for detecting genetic alterations. Liquid biopsies are more convenient and much less invasive than tissue biopsies and are useful for obtaining comprehensive genomic information on primary and metastatic tumors. Assessing ctDNA can help track genomic evolution and the status of alterations in genes such as RAS, which are sometimes altered following chemotherapy. In this review, we discuss the potential clinical applications of ctDNA, summarize clinical trials focusing on RAS, and present the future prospects of ctDNA analysis that could change daily clinical practice. Full article
(This article belongs to the Special Issue Chemotherapy for Colorectal Cancer)
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13 pages, 604 KiB  
Review
Molecular Basis of HER2-Targeted Therapy for HER2-Positive Colorectal Cancer
by Ayumu Yoshikawa and Yoshiaki Nakamura
Cancers 2023, 15(1), 183; https://doi.org/10.3390/cancers15010183 - 28 Dec 2022
Cited by 7 | Viewed by 2976
Abstract
Human epidermal growth factor receptor 2 (HER2) amplification has emerged as a biomarker in colorectal cancer (CRC), occurring in 1–4% of metastatic CRC (mCRC). In addition to conventional methods, such as immunohistochemistry and fluorescence in situ hybridization, next-generation sequencing-based tissue or [...] Read more.
Human epidermal growth factor receptor 2 (HER2) amplification has emerged as a biomarker in colorectal cancer (CRC), occurring in 1–4% of metastatic CRC (mCRC). In addition to conventional methods, such as immunohistochemistry and fluorescence in situ hybridization, next-generation sequencing-based tissue or circulating tumor DNA analysis has recently been used to identify HER2 amplification and assess HER2 overexpression. Prospective clinical trials have demonstrated the efficacy of HER2-targeted therapies in HER2-positive mCRC. The TRIUMPH study, a phase II study of dual HER2 antibodies, i.e., pertuzumab plus trastuzumab, demonstrated promising efficacy for patients with HER2-positive mCRC confirmed by tissue-and/or blood-based techniques, which led to the regulatory approval of this combination therapy in Japan. The mechanisms associated with efficacy and resistance have also been explored in translational studies that incorporate liquid biopsy in prospective trials. In particular, HER2 copy number and co-alterations have repeatedly been reported as biomarkers related to efficacy. To improve the therapeutic efficacy of the current strategy, many clinical trials with various HER2-targeted agents are ongoing. This review discusses the molecular basis of HER2-targeted therapeutic strategies for patients with HER2-positive mCRC. Full article
(This article belongs to the Special Issue Chemotherapy for Colorectal Cancer)
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