Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and is heterogeneous both morphologically and molecularly. In an era of personalized medicine, the greatest challenge is to predict individual response to therapy and distinguish patients likely to be cured with surgical resection of tumors and systemic therapy from those resistant or non-responsive to treatment. Patients would avoid futile treatments, including clinical trial regimes and ultimately this would prevent under- and over-treatment and reduce unnecessary adverse side effects. In this review, the potential of specific biomarkers will be explored to address two key questions-1) Can the prognosis of patients that will fare well or poorly be determined beyond currently recognized prognostic indicators? and 2) Can an individual patient's response to therapy be predicted and those who will most likely benefit from treatment/s be identified? Identifying and validating key prognostic and predictive biomarkers and an understanding of the underlying mechanisms of drug resistance and toxicity in CRC are important steps in order to personalize treatment. This review addresses recent data on biological prognostic and predictive biomarkers in CRC. In addition, patient cohorts most likely to benefit from currently available systemic treatments and/or targeted therapies are discussed in this review.
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http://dx.doi.org/10.3390/cancers12040812 | DOI Listing |
Tumori
December 2024
Hereditary Digestive Tract Tumors Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Background: Lynch syndrome (LS), an autosomal dominant disorder resulting from germline pathogenic variants in DNA mismatch repair genes, poses an elevated risk of developing different types of cancer, particularly colorectal and endometrial. Early identification of LS individuals is vital for implementing preventive measures. This study aims to assess the adherence rate of LS individuals to colorectal surveillance and identify influencing factors.
View Article and Find Full Text PDFBMC Cancer
December 2024
Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Background: Accurate prediction of pathological complete response (pCR) and disease-free survival (DFS) in locally advanced rectal cancer (LARC) patients undergoing neoadjuvant chemoradiotherapy (NCRT) is essential for formulating effective treatment plans. This study aimed to construct and validate the machine learning (ML) models to predict pCR and DFS using pathomics.
Method: A retrospective analysis was conducted on 294 patients who received NCRT from two independent institutions.
BMC Cancer
December 2024
Department of Medical Oncology, Division of Life Sciences and Medicine, The First Affiliated Hospital of University of Science and Technology of China (USTC), University of Science and Technology of China, Anhui Provincial Cancer Hospital, Hefei, 230001, China.
Background: The objective of this study is to investigate the potential association between change in body composition before and after cetuximab-based therapy and the prognostic outcomes among individuals diagnosed with advanced colorectal cancer.
Methods: A retrospective analysis was undertaken on a cohort of 81 patients diagnosed with RAS wild-type (WT) metastatic colorectal cancer (mCRC) who were treated with cetuximab-based first-line therapy. To assess relevant body composition parameters, quantitative computed tomography (QCT) scans were conducted both before and after cetuximab treatment.
Invest New Drugs
December 2024
Division of Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
Antiangiogenic drugs may cause vascular normalization and correct hypoxia in tumors, shifting cells to mitochondrial respiration as the primary source of energy. In turn, the addition of an inhibitor of mitochondrial respiration to antiangiogenic therapy holds potential to induce synthetic lethality. This study evaluated the mitochondrial inhibitor ME-344 in combination with bevacizumab in patients with refractory metastatic colorectal cancer (mCRC).
View Article and Find Full Text PDFOncogene
December 2024
Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Insufficient tumor cell-intrinsic interferon response represents a major obstacle in immune checkpoint blockade (ICB) therapy, particularly in anti-PD-1 treatment. Although cholesterol metabolism has been demonstrated to be a critical regulator of anti-tumor immune responses, whether cholesterol influences tumor cell-intrinsic interferon response in microsatellite instability (MSI) colorectal cancer (CRC) remains unknown. Through comprehensive siRNA library screening and Gene Set Enrichment Analysis (GSEA), we identified mevalonate kinase (MVK) as a crucial negative regulator of tumor cell-intrinsic interferon response in MSI CRC cells.
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