Review
Oncology
Guang Yang, Xi (Richard) Yu, Daniel J. J. Weisenberger, Tao Lu, Gangning Liang
Summary: Human colorectal cancer (CRC) is a global health burden, especially for minority populations. The disease is complex, with diverse molecular features linked to the location of the primary tumor, posing challenges to treatment and patient outcome improvement. Liver and other organ system metastases are major causes of CRC-related mortality and obstacles to improving outcomes. This review summarizes CRC tumor subgroups, molecular features, treatments, outcomes, and disparities in health and metastases.
Article
Biochemistry & Molecular Biology
Dasa Jevsinek Skok, Nina Hauptman
Summary: This article investigates the CpG island methylator phenotype (CIMP) in colorectal cancer development, using unsupervised hierarchical clustering to identify four distinct subtypes. Through mapping methylated regions to Ensembl database, 253 genes were found to exhibit aberrant methylation in promoter regions, with bone morphogenic protein 4 (BMP4) being highlighted as the most prominent candidate. This finding highlights the potential role of BMP4 in colorectal cancer development and progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Oscar Murcia, Alejandro Martinez-Roca, Miriam Juarez, Mar Giner-Calabuig, Miren Alustiza, Cristina Mira, Carolina Mangas-Sanjuan, Eva Serrano, Francisco Antonio Ruiz-Gomez, Sandra Baile-Maxia, Lucia Medina, Cristina Alenda, Artemio Paya, Maria Rodriguez-Soler, Pedro Zapater, Rodrigo Jover
Summary: The study suggests that CIMP may be a useful marker for endoscopic surveillance after polypectomy, improving the accuracy in predicting the risk of metachronous advanced colorectal lesions (MACLs). Patients with CIMP+ polyps show a higher risk and shorter time to MACL development, even after adjustment for other factors. The addition of CIMP analysis enhances the sensitivity, negative predictive value, and overall accuracy in estimating MACL risk.
Article
Multidisciplinary Sciences
Yuan-Chang Dai, Chuan-Yin Fang, Hsin-Yi Yang, Yi-Jun Jian, Shou-Chieh Wang, Yi-Wen Liu
Summary: Colorectal cancer (CRC) is a common malignancy in Taiwan and worldwide, with EMT playing a crucial role in its progression. The study investigates the correlation between EMT-related protein expression and clinicopathologic features of CRC in Taiwan, revealing associations with cancer stage, histopathologic grade, and other prognostic factors. Additionally, DNA methylation of the CD44 gene showed differences between tumor and non-tumor tissues, but may not be enough to inactivate the gene. The expression of E-cadherin, claudin-1, and nuclear beta-catenin was closely related to clinicopathologic prognostic determinants of CRC in Taiwan, while CD44 gene methylation level and protein expression showed no correlation with clinicopathologic features.
Review
Oncology
Hyun Jin Shin, Junjie T. Hua, Haolong Li
Summary: Epigenetic modifications, particularly DNA methylation, are extensively studied in cancer and have been shown to distinguish between benign and malignant tumors in various cancers, including prostate cancer. Aberrant DNA methylation patterns, such as the CpG island hypermethylator phenotype (CIMP), are associated with aggressive subtypes, higher Gleason score, and overall worse prognosis in prostate cancer. DNA methylation alterations can serve as potential biomarkers for prostate cancer and have the potential for targeted treatment development.
FRONTIERS IN ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Karpinski Pawel, Sasiadek Maria Malgorzata
Summary: The CpG island methylator phenotype (CIMP) is an important manifestation of epigenetic instability in cancer. It has been extensively studied in various tumor types, but its use as a diagnostic marker and therapeutic target in solid tumors is limited by the lack of generalizability and reproducibility of epigenetic markers, as well as its poor predictive value in clinical outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Valentina Condelli, Giovanni Calice, Alessandra Cassano, Michele Basso, Maria Grazia Rodriquenz, Angela Zupa, Francesca Maddalena, Fabiana Crispo, Michele Pietrafesa, Michele Aieta, Alessandro Sgambato, Giampaolo Tortora, Pietro Zoppoli, Matteo Landriscina
Summary: This study identified and validated a novel epigenetic eight-gene signature, with hypermethylation of the promoter regions, that can predict poor outcomes for a subgroup of metastatic colorectal carcinomas. The study showed that methylation events were enriched in genes located on specific chromosomal regions associated with adenoma-to-carcinoma progression, providing prognostic information for identifying metastatic colorectal carcinomas with poor prognosis.
Article
Oncology
Harumi Yamada, Hideyuki Takeshima, Ryoji Fujiki, Satoshi Yamashita, Shigeki Sekine, Takayuki Ando, Naoko Hattori, Atsushi Okabe, Takaki Yoshikawa, Kazutaka Obama, Hitoshi Katai, Atsushi Kaneda, Toshikazu Ushijima
Summary: The CpG island methylator phenotype (CIMP) is associated with prognosis and drug sensitivity in multiple cancer types. This study demonstrates that mutations in the SWI/SNF chromatin remodeling complex, particularly ARID1A, are associated with CIMP induction in gastric cancer, as well as in uterine endometrial and colorectal cancers. The loss of ARID1A function causes aberrant DNA methylation and is likely a potential mechanism for CIMP induction.
Article
Biochemistry & Molecular Biology
Seok-Byung Lim, Soobok Joe, Hyo-Ju Kim, Jong Lyul Lee, In Ja Park, Yong Sik Yoon, Chan Wook Kim, Jong-Hwan Kim, Sangok Kim, Jin-Young Lee, Hyeran Shim, Hoang Bao Khanh Chu, Sheehyun Cho, Jisun Kang, Si-Cho Kim, Hong Seok Lee, Young-Joon Kim, Seon-Young Kim, Chang Sik Yu
Summary: Aberrant DNA methylation plays a crucial role in the onset and progression of colorectal cancer (CRC) in Korea. Through methylation analysis of 172 tumors and 128 adjacent normal colon tissues, hypermethylated positions in tumors were found to be concentrated in CpG islands and promoter regions, while hypomethylated positions were mainly found in the open-sea regions away from CpG islands. Stratification of patients based on the CpG island methylator phenotype (CIMP) validated previous clinicopathological implications. This study provides valuable insights into the utilization of CRC-associated methylation markers in Korean patients and lays a solid foundation for further investigations into personalized and ethnicity-specific CRC treatments.
Article
Cell Biology
Qin Wang, Guangwei Zhu, Chunlin Lin, Penghang Lin, Hui Chen, Ruofan He, Yongjian Huang, Shugang Yang, Jianxin Ye
Summary: This study identified that AP-1 promotes the proliferation, migration, and invasion of colorectal cancer cells by activating the vimentin promoter. However, this effect was abolished when vimentin was knocked down. Animal experiments confirmed that AP-1 regulates tumor growth through vimentin.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Biochemical Research Methods
Josephine Yates, Valentina Boeva
Summary: This study utilized a pan-cancer approach to define and explore CpG island methylator phenotype (CIMP) in 26 cancer types. The results confirmed the existence of CIMP in 19 cancers, showed its association with survival differences in eight cancer types, and identified potential drivers of CIMP. The study also found that CIMP was strongly correlated with tumor microenvironment characteristics.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Sara Monteiro-Reis, Vera Miranda-Goncalves, Catarina Guimaraes-Teixeira, Claudia Martins-Lima, Joao Lobo, Diana Montezuma, Paula C. Dias, Helene Neyret-Kahn, Isabelle Bernard-Pierrot, Rui Henrique, Carmen Jeronimo
Summary: In this study, we found that the VIM promoter is epigenetically regulated in normal and neoplastic urothelium, leading to a switch in VIM expression associated with EMT and the acquisition of invasive and metastatic properties. These findings might contribute to the development of novel therapeutic strategies for bladder cancer based on epigenetics.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Alvaro Gutierrez, Hannah Demond, Priscilla Brebi, Carmen Gloria Ili
Summary: Colorectal cancer is the third most common cancer globally, and biomarkers play a crucial role in diagnosis and predicting metastasis. Key signaling pathways associated with cancer progression include the MAPK pathway, p53 pathway, and TGF-beta pathway.
Article
Oncology
Maria del Carmen Turpin-Sevilla, Fernando Perez-Sanz, Jose Garcia-Solano, Patricia Sebastian-Leon, Javier Trujillo-Santos, Pablo Carbonell, Eduardo Estrada, Anne Tuomisto, Irene Herruzo, Lochlan J. Fennell, Markus J. Makinen, Edith Rodriguez-Braun, Vicki L. J. Whitehall, Ana Conesa, Pablo Conesa-Zamora
Summary: Aberrant methylation patterns at specific genome sequences (CpG) are driving forces for carcinogenesis processes. Different histological subtypes of colorectal cancer (CRC) exhibit distinct global methylation patterns, with a shift from promoter hypermethylation to genomic hypomethylation occurring at a small sequence between 250 bp and 1 Kb from the gene TSS.
Article
Oncology
Sabine Meessen, Nicola Currey, Zeenat Jahan, Hannah W. Parker, Mark A. Jenkins, Daniel D. Buchanan, John L. Hopper, Eva Segelov, Jane E. Dahlstrom, Maija R. J. Kohonen-Corish
Summary: EMAST is a DNA mismatch repair defect related to MSI-H and MSI-L, with potential as a valuable prognostic and predictive marker for colorectal carcinomas.
Meeting Abstract
Oncology
Arvind Dasari, Maen Abdelrahim, Jared David Acoba, Krishna Chaitanya Alluri, Tomislav Dragovich, Syed Mohammad Ali Kazmi, Benjamin Leon Musher, Ryan Sun, Lucas Wong, Y. Nancy You, Robert Anthony Zaiden, Scott Kopetz
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Review
Oncology
Cathy Eng, Kristen K. Ciombor, May Cho, Jennifer A. Dorth, Lakshmi N. Rajdev, David P. Horowitz, Marc J. Gollub, Alexandre A. Jacome, Natalie A. Lockney, Roberta L. Muldoon, Mary Kay Washington, Brittany A. O'Brian, Amala Benny, Cody M. Lebeck Lee, Al B. Benson, Karyn A. Goodman, Van Karlyle Morris
Summary: The social stigma surrounding an anal cancer diagnosis has traditionally prevented open discussions about the disease, but awareness is growing with recent treatment options and an increasing rate of diagnoses. The main risk factor for anal cancer is human papillomavirus infection; patients with HIV are more likely to develop anal cancer. This article provides an overview of anal canal carcinoma, the role of screening, advancements in radiation therapy, and current trials investigating treatment-related toxicities.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Kanwal Raghav, Fang-Shu Ou, Alan P. Venook, Federico Innocenti, Ryan Sun, Heinz-Josef Lenz, Scott Kopetz
Summary: Clinical trial updates allow for dissemination of additional results from studies where the primary end point has already been reported. This study aimed to determine the prevalence of acquired genomic alterations (Acq-GAs) on anti-EGFR-chemotherapy compared to anti-VEGF-chemotherapy and later-line anti-EGFR-antibody therapy in metastatic colorectal cancer (mCRC). The findings indicate divergent resistance mechanisms with rare occurrence of Acq-GAs with up-front use of anti-EGFR-chemotherapy.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Veronika Fedirko, Scott Kopetz, Carrie R. Daniel
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Editorial Material
Oncology
Madhulika Eluri, Scott Kopetz, Christine M. Parseghian
Summary: The use of serial ctDNA in metastatic colorectal cancer has the potential to refine patient selection, reduce chemotherapy toxicity, and assess emerging resistance mechanisms for novel therapeutic strategies. However, important questions remain regarding its validation as a predictive biomarker of treatment response.
CLINICAL CANCER RESEARCH
(2023)
Letter
Oncology
Kanwal Raghav, Scott Kopetz, Ying Yuan
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Kristen K. Ciombor, Cathy Eng
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Andreana N. Holowatyj, Wanqing Wen, Timothy Gibbs, Hannah M. Seagle, Samantha R. Keller, Digna R. Velez Edwards, Mary K. Washington, Cathy Eng, Jose Perea, Wei Zheng, Xingyi Guo
Summary: This study investigated somatic mutation patterns in colorectal cancer patients of different races/ethnicities and sexes, finding that non-Hispanic Black and Asian/Pacific Islander patients with early-onset nonhypermutated colorectal cancer had higher tumor mutation rates compared to non-Hispanic white patients. Significant differences were observed in the mutation frequencies of several genes between racial/ethnic groups in early-onset nonhypermutated colorectal cancers. Furthermore, heterogeneity was observed in the effects of certain genes between early-onset and late-onset nonhypermutated colorectal cancer, as well as between males and females. These findings provide important insights into the genomic patterns and disparities of early-onset colorectal cancer based on race/ethnicity and sex.
Article
Medicine, General & Internal
Karl Bordeau, Morgan Michalet, Aicha Keskes, Simon Valdenaire, Pierre Debuire, Marie Cantaloube, Morgane Cabaille, William Jacot, Roxana Draghici, Sylvain Demontoy, Xavier Quantin, Marc Ychou, Eric Assenat, Thibault Mazard, Ludovic Gauthier, Marie Dupuy, Boris Guiu, Celine Bourgier, Norbert Ailleres, Pascal Fenoglietto, David Azria, Olivier Riou
Summary: Liver stereotactic body radiotherapy (SBRT) provides effective local control and minimal toxicity for liver metastases. This study presents the first clinical results of stereotactic MR-guided radiotherapy (MRgRT) for liver metastases from a prospective registry. The treatment was well-tolerated, with low rates of acute and late toxicities. The overall survival and local control rates were promising, but distant relapse remains a challenge.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Oncology
Karl Bordeau, Morgan Michalet, Aicha Keskes, Simon Valdenaire, Pierre Debuire, Marie Cantaloube, Morgane Cabaille, Fabienne Portales, Roxana Draghici, Marc Ychou, Eric Assenat, Thibault Mazard, Emmanuelle Samalin, Ludovic Gauthier, Pierre-Emmanuel Colombo, Sebastien Carrere, Francois-Regis Souche, Norbert Ailleres, Pascal Fenoglietto, David Azria, Olivier Riou
Summary: Stereotactic MR-guided Adaptive RadioTherapy (SMART) is a promising treatment for pancreatic tumors, providing effective and well-tolerated therapy. It has the potential to improve the management of pancreatic adenocarcinoma, but further studies are needed to confirm its exact role.
Article
Oncology
Blessie Elizabeth Nelson, Apostolia M. Tsimberidou, Xueyao Fu, Siqing Fu, Vivek Subbiah, Anil K. Sood, Jordi Rodon, Daniel D. Karp, George Blumenschein, Scott Kopetz, Shubham Pant, Sarina A. Piha-Paul
Summary: This study evaluated the combination of bevacizumab, temsirolimus, and valproic acid in patients with advanced malignancies and found modest efficacy but significant toxicity. The study is the first to evaluate this combination and suggests potential for anticancer activity, but careful management of toxicity is necessary for future development.
Article
Oncology
Hagen F. Kennecke, Rebecca Auer, May Cho, N. Arvind Dasari, Cynthia Davies-Venn, Cathy Eng, Jennifer Dorth, Julio Garcia-Aguilar, Manju George, Karyn A. Goodman, Lillian Kreppel, Joshua E. Meyer, Jose Monzon, Leonard Saltz, Deborah Schrag, J. Joshua Smith, Jason A. Zell, Prajnan Das, Natl Canc Inst Rectal Anal Task Force
Summary: The optimal management of locally advanced rectal cancer is rapidly evolving. A task force convened by the National Cancer Institute developed consensus on the design of future clinical trials for rectal cancer based on iterative reviews and a Delphi analytical approach. The task force achieved consensus on various aspects, including the use of neoadjuvant therapy, the importance of patient involvement, the identification of patients likely to benefit from nonoperative management or minimally invasive surgery, the utility of circulating tumor DNA measurements, and the need for appropriate end points and data management.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Biotechnology & Applied Microbiology
Himani Vaidya, Hye Seon Jeong, Kelsey Keith, Shinji Maegawa, Gennaro Calendo, Jozef Madzo, Jaroslav Jelinek, Jean-Pierre J. Issa
Summary: DNA methylation drift and increased entropy with age are primarily caused by and are sensors for, stem cell replication in adult tissues. These findings have implications for tissue-specific functional declines with aging and the development of DNA-methylation-based biological clocks.
Article
Oncology
Michael LaPelusa, Christopher Cann, Kristen K. Ciombor, Cathy Eng
Summary: This study examined the genetic mutations in pretreatment tumor tissue and posttreatment ctDNA in patients with metastatic SCCA and assessed the impact of therapy on the concordance between them. The results showed a high degree of temporal mutational heterogeneity in patients with SCCA, supporting the use of ctDNA as a real-time tracking mechanism for solid tumors' molecular evolution. The study also highlighted the potential of ctDNA in identifying emerging actionable mutations. Further research is needed to validate these findings.
Article
Oncology
Kyaw Z. Thein, Amadeo B. Biter, Kimberly C. Banks, Andrew W. Duda, Jennifer Saam, Jason Roszik, Filip Janku, Ferdinandos Skoulidis, John V. Heymach, Scott Kopetz, Funda Meric-Bernstam, David S. Hong
Summary: This study conducted a comprehensive analysis of KRAS(G12C) mutations in different types of cancer through liquid biopsy. The results showed that KRAS(G12C) mutations were detected in various cancers, with the highest detection rate in lung cancer.
JCO PRECISION ONCOLOGY
(2022)
