Why are colon cancer rates in young people rising? ColonCancer Cancer Oncology ColorectalCancer DanaFarber ScienceMagazine
By Neha MathurMar 21 2023Reviewed by Danielle Ellis, B.Sc. . So, they identified five critical areas for investigating EOCRC biology.Background In the United States of America , EOCRC, also known as young-onset colorectal cancer, is predicted to be the leading cause of death in individuals aged 20 to 49 years by 2030. Cases are increasing dramatically among people below 30 years in many countries, including low- and middle-income countries .
High levels of microsatellite instability in people with this syndrome also predispose them to other types of cancer. However, pathogenic germline variants observed in Lynch syndrome only partially contribute to the observed rise of EOCRC. Left-sided tumors have different embryologic origins, and they get exposed to variable factors along the gut, which elucidate varying mutational profiles observed across the colon. Due to this, next-generation sequencing panels profiling the somatic mutational landscape of EOCRCs find it tedious to define the molecular landscape of EOCRC, including its clinical and pathologic manifestations.
Cancer Research eBook Compilation of the top interviews, articles, and news in the last year. Download a free copy Transcriptional and epigenetic profiling of sporadic and inherited premalignant lesions also revealed changes along the CRC tumorigenesis. Together, these methods could uncover the pathophysiology of EOCRC, contrasting with LOCRC yet having some shared features too.
Metabolic syndromes, such as diabetes mellitus , have globally increased in recent decades, and these factors also possibly increase the CRC risk. In addition, there is an increased trend towards following unhealthy dietary regimens, e.g., processed meat, artificial flavors- and sugar-sweetened beverages, which also increase the risk of cancers, including CRC, in adolescents.
Conclusions An in-depth investigation of the interplay between the exposome, tumor-TME, and host is fundamental to revealing the reasons for an observed dramatic rise in the incidence of EOCRC.
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Exploring the Immunogenicity of Noncanonical HLA-I Tumor Ligands Identified through ProteogenomicsAbstractPurpose:. Tumor antigens are central to antitumor immunity. Recent evidence suggests that peptides from noncanonical (nonC) aberrantly translated proteins can be presented on HLA-I by tumor cells. Here, we investigated the immunogenicity of nonC tumor HLA-I ligands (nonC-TL) to better understand their contribution to cancer immunosurveillance and their therapeutic applicability.Experimental Design:. Peptides presented on HLA-I were identified in 9 patient-derived tumor cell lines from melanoma, gynecologic, and head and neck cancer through proteogenomics. A total of 507 candidate tumor antigens, including nonC-TL, neoantigens, cancer-germline, or melanocyte differentiation antigens, were tested for T-cell recognition of preexisting responses in patients with cancer. Donor peripheral blood lymphocytes (PBL) were in vitro sensitized against 170 selected nonC-TL to isolate antigen-specific T-cell receptors (TCR) and evaluate their therapeutic potential.Results:. We found no recognition of the 507 nonC-TL tested by autologous ex vivo expanded tumor-reactive T-cell cultures while the same cultures demonstrated reactivity to mutated, cancer-germline, or melanocyte differentiation antigens. However, in vitro sensitization of donor PBL against 170 selected nonC-TL, led to the identification of TCRs specific to three nonC-TL, two of which mapped to the 5′ UTR regions of HOXC13 and ZKSCAN1, and one mapping to a noncoding spliced variant of C5orf22C. T cells targeting these nonC-TL recognized cancer cell lines naturally presenting their corresponding antigens. Expression of the three immunogenic nonC-TL was shared across tumor types and barely or not detected in normal cells.Conclusions:. Our findings predict a limited contribution of nonC-TL to cancer immunosurveillance but demonstrate they may be attractive novel targets for widely applicable immunotherapies.
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