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Emerging Biomarkers and Targeted Therapies Reshaping Clinical Management of Colorectal Cancer

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Review Article

Emerging Biomarkers and Targeted Therapies Reshaping Clinical Management of Colorectal Cancer

  • Tamer A. Addissouky 123*
  • Ibrahim El Tantawy El Sayed 2
  • Majeed M. A. Ali 1

*Corresponding Author: Tamer A. Addissouky, Al-HADI University College, Baghdad. Iraq. - Department of Biochemistry, Science Faculty, Menoufia University, Egypt. - MLS ministry of health, Alexandria, Egypt. - MLS, ASCP, USA.

Citation: Tamer A. Addissouky, Ibrahim El Tantawy El Sayed, Majeed M. A. Ali, (2024), Emerging Biomarkers and Targeted Therapies Reshaping Clinical Management of Colorectal Cancer, J. Cancer Research and Cellular Therapeutics, 8(2); DOI:10.31579/2640-1053/184

Copyright: © 2024, Tamer A. Addissouky. this is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 24 January 2024 | Accepted: 01 February 2024 | Published: 28 February 2024

Keywords: colorectal cancer; immunotherapy targeted therapy; precision medicine biomarkers

Abstract

Background: Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Key risk factors include lifestyle, diet, inflammation, and family history. Understanding molecular pathways underlying CRC initiation and progression is critical to guide prevention and treatment.

Purpose: This review summarizes recent advances in CRC screening, therapy, and future directions.

Main body: New stool DNA panels and blood-based assays offer non-invasive options for early CRC detection, though require further validation. Immuno- and targeted therapies matched to tumor molecular profiles have transformed metastatic CRC treatment. Pembrolizumab elicits durable responses in mismatch repair-deficient tumors, and anti-EGFR antibodies cetuximab/panitumumab improve outcomes for left-sided RAS/RAF wild-type CRC. Larotrectinib and entrectinib are highly active in NTRK fusion-positive CRC. Research focusing on new immunotherapies, leveraging the microbiome, and combining multi-omics data to enable precision medicine holds promise. Disparities across groups remain a challenge. 

Conclusions: Recent therapeutic advances have significantly improved survival for metastatic CRC patients. Advances in non-invasive diagnostics, next-generation sequencing, and computational approaches will enable more sophisticated molecular profiling and tailored therapy selection. Realizing the potential of emerging immunotherapies and integrating knowledge of the microbiome remain important frontiers.

Background

Colorectal cancer (CRC) remains one of the most prevalent cancer diagnoses and leading causes of cancer mortality worldwide. Global disease burden has risen in tandem with adoption of certain dietary and lifestyle changes in economically transitioning countries. Understanding key risk factors and pathogenic mechanisms is imperative to guide prevention and treatment strategies [1-3]. Established environmental and lifestyle risk factors for CRC beyond screening non-adherence include smoking, heavy alcohol intake, obesity, consumption of processed or red meat, and low dietary fiber/vegetable intake. Chronic intestinal inflammation is also an important risk factor, as seen in inflammatory bowel disease. Family history of CRC confers increased risk, and several inherited cancer syndromes like Lynch syndrome dramatically predispose to early-onset CRC. Recently, the gut microbiome has emerged as a potentially important modifiable factor, though mechanisms require further characterization [4-8]. Understanding how these exposures drive CRC initiation and progression at the molecular level remains an area of active investigation. Key pathogenic pathways include chromosomal instability, microsatellite instability, and CpG island methylator phenotype pathways which dictate patterns of genetic mutations arising in tumors. Recent research has also focused on altered metabolic, inflammatory, and immune pathways within the tumor microenvironment which enable growth and metastasis [9].

Early Diagnosis and Screening

Detecting colorectal cancer (CRC) at an early stage is critical, as 5-year survival drops precipitously from 90% for localized disease to 14% for metastatic cancer. While screening has improved early diagnosis, novel modalities beyond colonoscopy and stool testing are emerging as depicted in table 1. In 2014, Cologuard, a multitarget stool DNA test, was FDA-approved for CRC screening based on superior sensitivity to standard fecal immunochemical testing. However, concerns remain regarding specificity. Plasma-based tests like Epi proColon (methylated SEPT9 DNA) and OncoBEAM (mutant KRAS/NRAS DNA) are now commercially available as screening tools, though evidence is still limited [10-11]. An area of active research is development of blood-based biomarkers for early detection. Circulating tumor cells (CTCs), cell-free tumor DNA, exosomes, miRNAs, proteins, and metabolites are all under study as non-invasive diagnostic markers. Recent advances have identified methylated gene panels, glycosylated protein markers, and metabolite signatures that can discriminate CRC from controls with high accuracy [12-24]. Machine learning and artificial intelligence tools applied to medical imaging and liquid biomarkers show enormous potential to transform early diagnosis. Deep learning algorithms can synthesize diverse data sources into predictive models. However, extensive further validation is required before clinical implementation [25-33]. While colonoscopy remains the gold standard, the advent of stool DNA panels, blood-based assays, and AI-enhanced imaging offer new options for non-invasive screening that could significantly improve early detection and save lives. But rigorous assessment of clinical utility and cost-effectiveness remains needed as these tools continue to evolve [34-35].

Table 1. Emerging Non-Invasive Screening Tests for Colorectal Cancer

Advances in Treatment and Innovative Therapeutics

The treatment landscape for colorectal cancer (CRC) has been transformed over the past decade by the arrival of new chemotherapeutic regimens, immunotherapies, targeted agents, and a growing emphasis on precision medicine. Significant gains have been made in systemic therapies for metastatic CRC, extending and improving quality of survival. Several new chemotherapy backbones and combinations have been established through positive randomized phase III trials and endorsed in clinical guidelines. The FOLFOXIRI regimen (folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan) plus bevacizumab has become a standard first-line option for eligible metastatic CRC patients based on significant extensions in median progression-free and overall survival compared to doublet chemotherapy plus bevacizumab. For patients progressing after first-line treatment, addition of the novel vascular endothelial growth factor (VEGF) inhibitors ramucirumab or regorafenib to continuous 5-fluorouracil-based chemotherapy was shown to provide a survival advantage. The multikinase inhibitor regorafenib also showed activity as monotherapy in phase III trials [36-37].

Beyond chemotherapy, arguably the most exciting advances have come in the form of immunotherapy and targeted therapies directed against specific molecular aberrations. After demonstrating remarkable activity in microsatellite instability-high (MSI-H) solid tumors, pembrolizumab and nivolumab have emerged as mainstream options for metastatic CRC patients whose tumors exhibit mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H). The pivotal phase II CheckMate-142 trial established pembrolizumab as an effective therapy for previously-treated MSI-H/dMMR metastatic CRC, eliciting an immune-related objective response rate of 31%. Building on this, KEYNOTE-177 established pembrolizumab monotherapy as superior to standard chemotherapy in the first-line setting for this population. Ongoing studies are assessing pembrolizumab in combination with chemotherapy backbone, epidermal growth factor receptor (EGFR) inhibitors, or MEK inhibitors as initial therapy for metastatic MSI-H/dMMR CRC. Beyond MSI-H/dMMR disease, research is ongoing into other potential immunotherapy biomarkers and rational combination strategies to extend benefit to broader groups of CRC patients [38-40]. In parallel, monoclonal antibodies and small molecule inhibitors targeting key oncogenic drivers matched to specific biomarkers have moved into standard practice. Cetuximab and panitumumab, monoclonal antibodies directed against EGFR, are now firmly established components of therapy for left-sided RAS/RAF wild-type metastatic CRC. Multiple trials have proven superior outcomes with the addition of these biologics to chemotherapy backbones for this molecularly defined population. Though less common, actionable NTRK and BRAF mutations also now have clinical grade targeted therapies. Larotrectinib and entrectinib, highly selective tropomyosin receptor kinase (TRK) inhibitors, elicit rapid and often durable responses in the small subset of CRC tumors harboring NTRK fusion genes. Encorafenib (BRAF inhibitor) combined with anti-EGFR antibody cetuximab shows excellent efficacy in BRAF-mutant CRC based on the BEACON trial. While these targets affect a smaller proportion of patients, the activity of matched targeted agents is dramatic and provides proof of concept for ongoing biomarker-driven drug development [41-43].

Traditional Medicine

Some traditional herbal medicines and practices derived from ancient healing systems have shown potential anti-cancer benefits against colorectal cancer in preliminary cell line, animal, and early human studies. Most mechanisms relate to anti-inflammatory, antioxidant, and anti-proliferative properties. Curcumin, a polyphenol derived from turmeric, can inhibit growth and metastasis of colorectal cancer cells through regulating multiple signaling pathways. A small clinical trial in colorectal cancer patients found curcumin combined with chemotherapy reduced tumor cell proliferation compared to chemotherapy alone. Other polyphenols like EGCG from green tea, resveratrol from grapes, and silibinin from milk thistle also demonstrate anti-cancer effects. The traditional Chinese medicine formula PHY906, containing Scutellaria baicalensis (Huang Qin), has been shown in mouse models to normalize intestinal microbiota and reduce chemotherapy-induced toxicity. A phase I/II trial in patients with advanced colorectal cancer suggested PHY906 plus capecitabine improves progression-free survival compared to capecitabine alone. Larger randomized trials of PHY906 are underway [44-47]. 

Nanomedicine

Nanomedicine utilizes specially engineered nanoparticles (NPs) sized 1-100 nm for cancer imaging, drug delivery, and theranostics. Over the past decade, NP platforms have made significant progress towards clinical implementation for colorectal cancer. Dozens of NP constructs have been studied for colorectal cancer drug delivery, including liposomes, dendrimers, carbon nanotubes, and inorganic nanoparticles. Liposomal irinotecan received FDA approval in 2015 based on improved progression-free survival compared to standard irinotecan in metastatic colorectal cancer. Iron oxide, gold, and silica NPs have demonstrated potential as highly sensitive contrast agents for enhanced colorectal cancer imaging. Tumor-targeted gold NPs also enable photothermal ablation of tumors when exposed to near infrared light. An exciting development is the emergence of theranostics - NPs that integrate therapy and diagnostics into a single platform. For example, new approaches use fluorescent silica NPs to improve tumor visualization during surgery, while loaded with chemotherapeutics for sustained postoperative treatment [48-50].

Future Directions

While recent years have seen impressive advances in colorectal cancer across multiple fronts, significant opportunities and challenges remain to further progress. Exciting new innovations in treatment, diagnostics, and prevention on the horizon warrant expanded research. Novel immunotherapies offer new paradigms in activating anti-tumor immunity. Beyond immune checkpoint inhibitors like pembrolizumab, ongoing research is exploring cancer vaccines, CAR T cells, oncolytic viruses, and combination immunotherapies. These approaches aim to generate more durable responses than current options [51-53]. Leveraging the microbiome therapeutically also holds promise. Fecal microbial transplantation to restore intestinal homeostasis and probiotics/prebiotics to prevent colitis show potential to reduce colorectal cancer risk. Additional research is needed to identify mechanisms and optimal approaches [54-56]. Expanding our understanding of colorectal cancer genetics and immunology will enable more sophisticated molecular profiling, guiding personalized precision medicine. Multi-omics integration and systems biology modeling will provide a more comprehensive view of CRC carcinogenesis [57]. Detecting pre-malignant polyps and early-stage tumors remains challenging. Development and validation of blood or stool biomarkers, through proteomics, metabolomics, and epigenetics, is a key priority. AI-enhanced imaging and endoscopy could also improve screening [58-59]. Disparities persist in CRC incidence and outcomes across socioeconomic, geographic, and racial/ethnic groups. Resolving these inequities requires coordinated efforts targeting risk factor reduction, screening access, diagnosis delays, and treatment availability [60]. Multidisciplinary collaboration harnessing new technologies will accelerate progress against colorectal cancer. Advances in genomics, immunotherapy, nanomedicine, applied AI, and precision diagnostics bring hope for improved outcomes and will shape the future of CRC research.

Conclusions:

Recent years have witnessed remarkable progress in the treatment of metastatic colorectal cancer, with median overall survival improving from around 12 months with older chemotherapy regimens to over 30 months with modern combination strategies incorporating targeted agents and immunotherapies matched to specific biomarkers. Looking forward, leveraging rapid advances across fields including genomics, immunotherapy, nanotechnology, and artificial intelligence offers immense opportunities to further advance screening, diagnosis, prevention, and therapeutic decision-making for colorectal cancer. Key priorities include developing and validating non-invasive biomarker approaches to enable earlier detection, expanding insights into colorectal cancer genetics and immunology to extend precision medicine approaches to larger groups of patients, further characterizing the role of the microbiome in colorectal carcinogenesis and response to therapy, designing innovative clinical trial methodologies to efficiently assess emerging immunotherapies and targeted agents matched to lower frequency biomarkers, and applying cutting-edge computational tools to synthesize diverse multi-omics data sources into predictive models guiding personalized therapy selection while accounting for inter- and intra-tumor heterogeneity. 

Recommendations:

Several recommendations can be made to accelerate progress against colorectal cancer:

  • Expand research and clinical validation of emerging non-invasive screening technologies like stool/blood biomarker panels and AI-enhanced medical imaging to improve early detection.
  • Develop and implement standardized molecular profiling of colorectal tumors at diagnosis using next-generation sequencing and immunohistochemistry to match patients to targeted therapies and immunotherapies. 
  • Design and support innovative clinical trials focusing on novel immunotherapies, integrating multi-omics data, and utilizing master protocols that assign therapy by genomic profile rather than cancer type.
  • Investigate the therapeutic potential of the gut microbiome through basic mechanistic studies and clinical trials of interventions like fecal transplant, pre/probiotics, and synbiotics.
  • Promote data sharing, collaboration between academia and industry, and leverage big data and AI to enable precision oncology and understand mechanisms of treatment resistance.
  • Prioritize reducing disparities in prevention, screening, diagnosis, and treatment across all populations through coordinated policy and community outreach efforts.
  • Fund research into novel nanotechnology platforms for colorectal cancer drug delivery, theranostics, and enhanced imaging.
  • Train more clinician-scientists qualified to advance molecular pathology, computational biology, immunotherapy, and clinical trials focused on targeted therapies.

Abbreviations:

CRC - Colorectal Cancer

EGFR - Epidermal Growth Factor Receptor

CMS - Consensus Molecular Subtypes

NPs - Nanoparticles

AI - Artificial Intelligence

FIT - Fecal Immunochemical Test

dMMR - Mismatch Repair Deficient

MSI-H - Microsatellite Instability-High

PD-1 - Programmed Death-1

PFS - Progression-Free Survival

OS - Overall Survival

Declarations:

Ethics approval and consent to participate: Not Applicable

Consent for publication: Not Applicable

Availability of data and materials: all data are available and sharing is available as well as publication.

Competing interests: The authors hereby that they have no competing interests.

Funding: Corresponding author supplied all study materials. There was no further funding for this study.

Authors' contributions: The authors completed the study protocol and were the primary organizers of data collection and the manuscript's draft and revision process. Tamer A. Addissouky wrote the article and ensured its accuracy. All authors contributed to the discussion, assisted in designing the study and protocol and engaged in critical discussions of the draft manuscript.

Acknowledgements: 

The authors thank all the researchers, editors, reviewers, and the supported universities that have done great efforts on their studies. Moreover, we are grateful to the editors, reviewers, and reader of this journal.

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Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

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Virginia E. Koenig

Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

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Delcio G Silva Junior

Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

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Ziemlé Clément Méda

Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.

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Mina Sherif Soliman Georgy

We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.

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Layla Shojaie

The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.

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Sing-yung Wu

Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.

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Orlando Villarreal

Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

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Katarzyna Byczkowska

Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

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Anthony Kodzo-Grey Venyo

Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

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Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

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Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

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Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

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Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

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Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

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Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

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Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

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Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

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Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

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Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

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Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

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Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

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Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

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Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

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Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

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S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

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Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

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George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

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Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

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Khurram Arshad

Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.

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Gomez Barriga Maria Dolores

The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.

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Lin Shaw Chin

Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.

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Maria Dolores Gomez Barriga

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.

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Dr Maria Dolores Gomez Barriga

Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.

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Dr Maria Regina Penchyna Nieto

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.

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Dr Marcelo Flavio Gomes Jardim Filho

Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”

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Zsuzsanna Bene

Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner

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Dr Susan Weiner