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Cancers
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Perspectives on the Efficacy and Biomarkers of Immunotherapy and Targeted...
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Perspectives on the Efficacy and Biomarkers of Immunotherapy and Targeted Therapy for Patients with Colorectal Cancer

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

Deadline for manuscript submissions: 31 December 2025 | Viewed by 4235

Special Issue Editor

Dr. Ibrahim Halil Sahin

E-Mail Website
Guest Editor
Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Interests: gastrointestinal oncology; targeted therapy; immunotherapy

Special Issue Information

Dear Colleagues,

In this Special Issue, we intend to provide a comprehensive update on precision medicine treatments and immunotherapeutics for patients with colorectal cancer. The scope of this Special Issue will include the efficacy of novel targeted therapeutic agents and immune checkpoint inhibitors, treatment-related adverse events and their management and the role of biomarkers for treatment selection as well as molecular underpinnings of mechanisms of resistance covering these novel agents.

This Special Issue aims to focus on these topics, amongst others. In this Special Issue, original research articles and reviews are welcome.

I look forward to receiving your contributions.

Dr. Ibrahim Halil Sahin
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

  • colorectal cancer
  • precision medicine
  • targeted therapeutics
  • immunotherapy
  • KRAS
  • BRAF
  • HER2
  • biomarkers

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (2 papers)

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Research

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12 pages, 1173 KB  
Article
A Comprehensive Molecular and Clinical Study of Patients with Young-Onset Colorectal Cancer
by Elham Nasrollahi, Shuaichao Wang, Rami Yanes, Cyndi Gonzalez Gomez, Tara Magge, Abigail Overacre, Ronan Hsieh, Ashley Mcfarquhar, Curtis Tatsuoka, Aatur Singhi, Anwaar Saeed and Ibrahim Halil Sahin
Cancers 2025, 17(17), 2763; https://doi.org/10.3390/cancers17172763 - 25 Aug 2025
Viewed by 627
Abstract
Background: Young-onset colorectal cancer (YO-CRC) has emerged as a distinct clinical entity, often presenting at advanced stages. Despite the increasing incidence, the molecular and clinical underpinnings of YO-CRC remain underexplored. This study aims to characterize the clinical and molecular features of YO-CRC [...] Read more.
Background: Young-onset colorectal cancer (YO-CRC) has emerged as a distinct clinical entity, often presenting at advanced stages. Despite the increasing incidence, the molecular and clinical underpinnings of YO-CRC remain underexplored. This study aims to characterize the clinical and molecular features of YO-CRC and to evaluate their impact on OS. Methods: We reviewed 110 patients diagnosed with YO-CRC at our institution who underwent next-generation sequencing. Demographic, clinical, and molecular data, including age, gender, race, tumor location, cancer stage, and mutation status (KRAS, NRAS, BRAF, POLE, ERBB-2/HER2, microsatellite status), were collected by reviewing electronic medical records. For OS analysis, we focused on patients diagnosed with de novo stage IV. Cox proportional hazards regression and Kaplan–Meier survival analysis were utilized to assess the association of these factors with OS, with statistical significance determined by a p-value threshold of <0.05. Results: Among 110 patients, n = 44 (40%) presented with local disease (stage 1–3), while n = 66 (60%) presented with de novo metastatic disease at the time of diagnosis. The median age at diagnosis was 44.5 years. The cohort consisted of 64% males and 36% females, with 84% of patients identified as White. Most tumors were left-sided (77%), including the distal colon/sigmoid (44%) and rectum (33%). KRAS and BRAF mutations were present in 36% and 5.5%, respectively. ERBB-2/HER2 amplification and microsatellite instability were observed in 4.5% and 6.4%, respectively. Tumor mutation burden (TMB) was <10 in 57% of patients, with 14% having TMB > 20. CNV analysis revealed that 14% of patients had copy gains, 12% had concurrent gains/losses, and 31% had copy losses. Among 66 patients with de novo metastatic disease, 44% had died by the time of analysis, with a median overall survival (OS) of 43.6 months (95% CI, 28.7—not reached). KRAS mutations were found to be significantly associated with worse survival outcomes. Cox regression analysis reveals the prognostic significance of KRAS status, with a hazard ratio (HR) of 3.52 (95% CI: 1.59–7.76, p = 0.002), indicating a significantly higher risk of death for KRAS-mutant YO-CRC patients. Conclusions: Patients with YO-CRC are more likely to present with de novo metastatic disease and left-sided tumors with distinct molecular characteristics. KRAS mutations are a key prognostic factor in YO-CRC, highlighting the need for therapeutic interventions to improve outcomes in this high-risk group. Full article
(This article belongs to the Special Issue Perspectives on the Efficacy and Biomarkers of Immunotherapy and Targeted Therapy for Patients with Colorectal Cancer)
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Review

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20 pages, 963 KB  
Review
Targeting the KRAS Oncogene for Patients with Metastatic Colorectal Cancer
by Ruoyu Miao, James Yu and Richard D. Kim
Cancers 2025, 17(9), 1512; https://doi.org/10.3390/cancers17091512 - 30 Apr 2025
Cited by 3 | Viewed by 3105
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide, with KRAS mutations occurring in approximately 40% of cases. These mutations drive tumorigenesis through the constitutive activation of key signaling pathways, such as RAS-RAF-MEK-ERK (MAPK) and PI3K-AKT-mTOR, contributing to therapeutic resistance and [...] Read more.
Colorectal cancer (CRC) is one of the most common cancers worldwide, with KRAS mutations occurring in approximately 40% of cases. These mutations drive tumorigenesis through the constitutive activation of key signaling pathways, such as RAS-RAF-MEK-ERK (MAPK) and PI3K-AKT-mTOR, contributing to therapeutic resistance and poor prognosis. Advances in molecular biology have led to significant breakthroughs, including the development of KRAS G12C inhibitors, such as sotorasib and adagrasib, which have shown promise in clinical trials. However, their efficacy is limited to a small subset of KRAS-mutant CRC, and resistance mechanisms often emerge through compensatory pathway activation. Combination strategies, including KRAS inhibitors with anti-EGFR agents, have been explored in trials like KRYSTAL-1 and CodeBreaK 300. Emerging research highlights the role of the tumor microenvironment in immune evasion and therapeutic resistance, offering opportunities for novel immunotherapy approaches, including KRAS neoantigen vaccines and adoptive T-cell therapy. Despite these advancements, challenges such as intratumoral heterogeneity, limited immune infiltration, and non-G12C KRAS mutations remain significant hurdles. This review provides a comprehensive overview of the molecular mechanisms, current advances and challenges, and future prospects in the management of KRAS-mutant CRC. Full article
(This article belongs to the Special Issue Perspectives on the Efficacy and Biomarkers of Immunotherapy and Targeted Therapy for Patients with Colorectal Cancer)
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