Incorporating Novel Technologies in Precision Oncology for Colorectal Cancer: Advancing Personalized Medicine

Simple Summary Cancer affects millions of individuals every year, with colorectal cancer being among the most common. There is an increased need to identify new biomarkers that can not only diagnose patients early, but also stratify them so the best treatment can be initiated for each patient. Every human has a unique genetic makeup that causes them to respond differently to cancer. In recent years, new technologies have provided unprecedented access to tumor samples from patients. Through these analyses, we can not only diagnose and classify patients based on their comparative risk, but also monitor their response to emerging therapies. Continued progress using these methods will transform how we approach treatment modalities for cancer patients. Abstract Colorectal cancer (CRC) is one of the most heterogeneous and deadly diseases, with a global incidence of 1.5 million cases per year. Genomics has revolutionized the clinical management of CRC by enabling comprehensive molecular profiling of cancer. However, a deeper understanding of the molecular factors is needed to identify new prognostic and predictive markers that can assist in designing more effective therapeutic regimens for the improved management of CRC. Recent breakthroughs in single-cell analysis have identified new cell subtypes that play a critical role in tumor progression and could serve as potential therapeutic targets. Spatial analysis of the transcriptome and proteome holds the key to unlocking pathogenic cellular interactions, while liquid biopsy profiling of molecular variables from serum holds great potential for monitoring therapy resistance. Furthermore, gene expression signatures from various pathways have emerged as promising prognostic indicators in colorectal cancer and have the potential to enhance the development of equitable medicine. The advancement of these technologies for identifying new markers, particularly in the domain of predictive and personalized medicine, has the potential to improve the management of patients with CRC. Further investigations utilizing similar methods could uncover molecular subtypes specific to emerging therapies, potentially strengthening the development of personalized medicine for CRC patients.

[1]  Liaoran Niu,et al.  Single-cell analysis unveils activation of mast cells in colorectal cancer microenvironment , 2023, Cell & Bioscience.

[2]  F. Finotello,et al.  Single cell dynamics of tumor specificity vs bystander activity in CD8+ T cells define the diverse immune landscapes in colorectal cancer , 2023, Cell discovery.

[3]  S. Zhuo,et al.  A nomogram based on collagen signature for predicting the immunoscore in colorectal cancer , 2023, Frontiers in immunology.

[4]  Wenchuan Wu,et al.  The evolution and heterogeneity of neutrophils in cancers: origins, subsets, functions, orchestrations and clinical applications , 2023, Molecular Cancer.

[5]  Rania A. Elsayed,et al.  Internet of Medical Things and Healthcare 4.0: Trends, Requirements, Challenges, and Research Directions , 2023, Sensors.

[6]  A. Hakimi,et al.  A multimodal atlas of tumour metabolism reveals the architecture of gene–metabolite covariation , 2023, Nature Metabolism.

[7]  Wei Zhang,et al.  Single-cell sequencing technology in colorectal cancer: a new technology to disclose the tumor heterogeneity and target precise treatment , 2023, Frontiers in Immunology.

[8]  S. Lee,et al.  Single-cell and spatial sequencing application in pathology , 2023, Journal of pathology and translational medicine.

[9]  S. Bullman,et al.  Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer , 2022, Nature.

[10]  Xiaohui Xie,et al.  A novel senescence-related lncRNA signature that predicts prognosis and the tumor microenvironment in patients with lung adenocarcinoma , 2022, Frontiers in Genetics.

[11]  Michael R Hamblin,et al.  Tumor-derived exosomal non-coding RNAs as diagnostic biomarkers in cancer , 2022, Cellular and Molecular Life Sciences.

[12]  Jing-Yuan Fang,et al.  Amino acid metabolism-based molecular classification of colon adenocarcinomavia in silico analysis , 2022, Frontiers in Immunology.

[13]  Lin Feng,et al.  Decoding the colorectal cancer ecosystem emphasizes the cooperative role of cancer cells, TAMs and CAFsin tumor progression , 2022, Journal of Translational Medicine.

[14]  F. Chibon,et al.  CINSARC signature outperforms gold-standard TNM staging and consensus molecular subtypes for clinical outcome in stage II–III colorectal carcinoma , 2022, Modern Pathology.

[15]  Evan Z. Macosko,et al.  The expanding vistas of spatial transcriptomics , 2022, Nature Biotechnology.

[16]  J-J Zheng,et al.  Identification of ferroptosis-related genes for the prediction of prognosis and chemotherapy benefit of gastric cancer. , 2022, European review for medical and pharmacological sciences.

[17]  P. Allavena,et al.  Macrophages as tools and targets in cancer therapy , 2022, Nature Reviews Drug Discovery.

[18]  Zhan-tao Xie,et al.  Single‐cell landscape and clinical outcomes of infiltrating B cells in colorectal cancer , 2022, Immunology.

[19]  Tengyu Ma,et al.  A novel senescence-associated LncRNA signature predicts the prognosis and tumor microenvironment of patients with colorectal cancer: a bioinformatics analysis , 2022, Journal of Gastrointestinal Oncology.

[20]  A. Kalmár,et al.  A Detailed Overview About the Single-Cell Analyses of Solid Tumors Focusing on Colorectal Cancer , 2022, Pathology oncology research : POR.

[21]  Zhiwei Peng,et al.  Spatial transcriptomics atlas reveals the crosstalk between cancer-associated fibroblasts and tumor microenvironment components in colorectal cancer , 2022, Journal of translational medicine.

[22]  Xiaofeng Dai,et al.  Advances and Trends in Omics Technology Development , 2022, Frontiers in Medicine.

[23]  Yang Li,et al.  Identification of Endoplasmic Reticulum Stress-Related Subtypes, Infiltration Analysis of Tumor Microenvironment, and Construction of a Prognostic Model in Colorectal Cancer , 2022, Cancers.

[24]  S. Prabhakar,et al.  Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer , 2022, Nature Genetics.

[25]  Konstantinos I. Kotis,et al.  A Smarter Health through the Internet of Surgical Things , 2022, Sensors.

[26]  R. Pilloton,et al.  State of the Art in Smart Portable, Wearable, Ingestible and Implantable Devices for Health Status Monitoring and Disease Management , 2022, Sensors.

[27]  Guanyu Yu,et al.  Development and Validation of an 8-Gene Signature to Improve Survival Prediction of Colorectal Cancer , 2022, Frontiers in Oncology.

[28]  Hao Zheng,et al.  Multi-Omics Characterization of a Glycerolipid Metabolism-Related Gene Enrichment Score in Colon Cancer , 2022, Frontiers in Oncology.

[29]  S. Poyarkov,et al.  Transcriptomic signatures in colorectal cancer progression. , 2022, Current molecular medicine.

[30]  F. Gao,et al.  DNA Repair–Related Gene Signature in Predicting Prognosis of Colorectal Cancer Patients , 2022, Frontiers in Genetics.

[31]  F. Ginhoux,et al.  Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancer , 2022, Nature Communications.

[32]  Tariq Ahmad Masoodi,et al.  Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments , 2022, Molecular Cancer.

[33]  A. Bardelli,et al.  Liquid biopsies to monitor and direct cancer treatment in colorectal cancer , 2022, British Journal of Cancer.

[34]  Xue Liang,et al.  Single‐cell RNA sequencing technologies and applications: A brief overview , 2022, Clinical and translational medicine.

[35]  L. P. Verhagen,et al.  Understanding natural killer cell biology from a single cell perspective. , 2022, Cellular immunology.

[36]  Peter Smibert,et al.  Multiplexed single-cell analysis reveals prognostic and nonprognostic T cell types in human colorectal cancer , 2022, JCI insight.

[37]  A. Rojiani,et al.  Clinical and molecular assessment of an onco‐immune signature with prognostic significance in patients with colorectal cancer , 2022, Cancer medicine.

[38]  Jordi Vitrià,et al.  Artificial intelligence to improve polyp detection and screening time in colon capsule endoscopy , 2022, Frontiers in Medicine.

[39]  Y. Morine,et al.  A transcriptomic signature that predicts cancer recurrence after hepatectomy in patients with colorectal liver metastases. , 2022, European journal of cancer.

[40]  S. Toden,et al.  Non-coding RNAs as liquid biopsy biomarkers in cancer , 2022, British Journal of Cancer.

[41]  D. Hanahan Hallmarks of Cancer: New Dimensions. , 2022, Cancer discovery.

[42]  A. Leiser,et al.  Real-world application of tumor mutational burden-high (TMB-high) and microsatellite instability (MSI) confirms their utility as immunotherapy biomarkers , 2021, ESMO open.

[43]  Changping Wu,et al.  The Role of the Tumor Microenvironment and Treatment Strategies in Colorectal Cancer , 2021, Frontiers in Immunology.

[44]  Xu-tao Lin,et al.  Identification of an Autophagy-Related Gene Signature for the Prediction of Prognosis in Early-Stage Colorectal Cancer , 2021, Frontiers in Genetics.

[45]  Qian Li,et al.  Recent Metabolomics Analysis in Tumor Metabolism Reprogramming , 2021, Frontiers in Molecular Biosciences.

[46]  R. Labianca,et al.  Early-Onset Colorectal Adenocarcinoma in the IDEA Database: Treatment Adherence, Toxicities, and Outcomes With 3 and 6 Months of Adjuvant Fluoropyrimidine and Oxaliplatin , 2021, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[47]  Xiaojian Wu,et al.  Cancer-associated fibroblasts impact the clinical outcome and treatment response in colorectal cancer via immune system modulation: a comprehensive genome-wide analysis , 2021, Molecular Medicine.

[48]  Min Liu,et al.  Comprehensive Analysis to Identify the Epithelial–Mesenchymal Transition-Related Immune Signatures as a Prognostic and Therapeutic Biomarkers in Hepatocellular Carcinoma , 2021, Frontiers in Surgery.

[49]  M. Bizzarri,et al.  Personalization of medical treatments in oncology: time for rethinking the disease concept to improve individual outcomes , 2021, EPMA Journal.

[50]  Dawei Jiang,et al.  Characterizing Intercellular Communication of Pan-Cancer Reveals SPP1+ Tumor-Associated Macrophage Expanded in Hypoxia and Promoting Cancer Malignancy Through Single-Cell RNA-Seq Data , 2021, Frontiers in Cell and Developmental Biology.

[51]  W. Liang,et al.  The association between CD8+ tumor-infiltrating lymphocytes and the clinical outcome of cancer immunotherapy: A systematic review and meta-analysis , 2021, EClinicalMedicine.

[52]  Yanqiao Zhang,et al.  Corrigendum: ENC1 Facilitates Colorectal Carcinoma Tumorigenesis and Metastasis via JAK2/STAT5/AKT Axis-Mediated Epithelial Mesenchymal Transition and Stemness , 2021, Frontiers in Cell and Developmental Biology.

[53]  Stephen R. Williams,et al.  A single-cell and spatially resolved atlas of human breast cancers , 2021, Nature Genetics.

[54]  Ruibin Xi,et al.  Spatiotemporal Immune Landscape of Colorectal Cancer Liver Metastasis at Single-Cell Level. , 2021, Cancer discovery.

[55]  D. Chan,et al.  Tumour heterogeneity and evolutionary dynamics in colorectal cancer , 2021, Oncogenesis.

[56]  Liren Li,et al.  Molecular subtype identification and prognosis stratification by a metabolism-related gene expression signature in colorectal cancer , 2021, Journal of Translational Medicine.

[57]  A. Ganesan,et al.  Spatial transcriptomics using combinatorial fluorescence spectral and lifetime encoding, imaging and analysis , 2021, Nature Communications.

[58]  Xiaojian Wu,et al.  Genome-Wide Analysis Reveals Hypoxic Microenvironment Is Associated With Immunosuppression in Poor Survival of Stage II/III Colorectal Cancer Patients , 2021, Frontiers in Medicine.

[59]  S. Reddy,et al.  Mast Cells: A New Frontier for Cancer Immunotherapy , 2021, Cells.

[60]  Qiu Lin,et al.  A New Oxaliplatin Resistance-Related Gene Signature With Strong Predicting Ability in Colon Cancer Identified by Comprehensive Profiling , 2021, Frontiers in Oncology.

[61]  J Zhang,et al.  Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer , 2021, Nature Communications.

[62]  Ying Cui,et al.  ENC1 Facilitates Colorectal Carcinoma Tumorigenesis and Metastasis via JAK2/STAT5/AKT Axis-Mediated Epithelial Mesenchymal Transition and Stemness , 2021, Frontiers in Cell and Developmental Biology.

[63]  D. Schrag,et al.  Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. , 2021, JAMA.

[64]  R. Kolhe,et al.  The clinical relevance of gene expression based prognostic signatures in colorectal cancer. , 2021, Biochimica et biophysica acta. Reviews on cancer.

[65]  R. Kamm,et al.  Engineering approaches for studying immune-tumor cell interactions and immunotherapy , 2020, iScience.

[66]  Kai Yin,et al.  Myeloid-Derived Suppressor Cells: A New and Pivotal Player in Colorectal Cancer Progression , 2020, Frontiers in Oncology.

[67]  Jun Yu,et al.  The role of natural killer cell in gastrointestinal cancer: killer or helper , 2020, Oncogene.

[68]  R. Bristow,et al.  Early Adaptation of Colorectal Cancer Cells to the Peritoneal Cavity Is Associated with Activation of “Stemness” Programs and Local Inflammation , 2020, Clinical Cancer Research.

[69]  Zhenguang Wang,et al.  Re-Evaluation of the Survival Paradox Between Stage IIB/IIC and Stage IIIA Colon Cancer , 2020, Frontiers in Oncology.

[70]  A. Goodman,et al.  The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker. , 2020, Cancer cell.

[71]  T. Kuijpers,et al.  Plasticity in Pro- and Anti-tumor Activity of Neutrophils: Shifting the Balance , 2020, Frontiers in Immunology.

[72]  Wei Zhang,et al.  Landscape of cell heterogeneity and evolutionary trajectory in ulcerative colitis-associated colon cancer revealed by single-cell RNA sequencing , 2020, Chinese journal of cancer research = Chung-kuo yen cheng yen chiu.

[73]  Richard T. Barfield,et al.  Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival , 2020, Nature Communications.

[74]  R. Labianca,et al.  Localised Colon Cancer: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. , 2020, Annals of oncology : official journal of the European Society for Medical Oncology.

[75]  N. Nagarajan,et al.  Human Tumor-Infiltrating MAIT Cells Display Hallmarks of Bacterial Antigen Recognition in Colorectal Cancer , 2020, Cell reports. Medicine.

[76]  M. Griffin,et al.  Human Monocyte Subset Distinctions and Function: Insights From Gene Expression Analysis , 2020, Frontiers in Immunology.

[77]  T. Hinks,et al.  MAIT Cell Activation and Functions , 2020, Frontiers in Immunology.

[78]  Y. Yatabe,et al.  Tumor Location Is Associated With the Prevalence of Braf And Pik3ca Mutations in Patients with Wild-Type Ras Colorectal Cancer: A Prospective Multi-Center Cohort Study in Japan , 2020, Translational oncology.

[79]  J. Carles,et al.  Evolving Landscape of Molecular Prescreening Strategies for Oncology Early Clinical Trials , 2020, JCO precision oncology.

[80]  Ye Wang,et al.  Changing Technologies of RNA Sequencing and Their Applications in Clinical Oncology , 2020, Frontiers in Oncology.

[81]  Deepali V. Sawant,et al.  Single-Cell Analyses Inform Mechanisms of Myeloid-Targeted Therapies in Colon Cancer , 2020, Cell.

[82]  J. Meyerhardt,et al.  Metabolic Profiling of Formalin-Fixed Paraffin-Embedded Tissues Discriminates Normal Colon from Colorectal Cancer , 2020, Molecular Cancer Research.

[83]  Rob Knight,et al.  Microbiome analyses of blood and tissues suggest cancer diagnostic approach , 2020, Nature.

[84]  T. Schumacher,et al.  CD8+ T cell states in human cancer: insights from single-cell analysis , 2020, Nature Reviews Cancer.

[85]  E. G. Nabel,et al.  National Cancer Institute , 2020, Definitions.

[86]  Binbin Cui,et al.  Colorectal cancer-derived exosomal miR-106b-3p promotes metastasis by downregulating DLC-1 expression. , 2020, Clinical science.

[87]  S. Haan,et al.  Prognostic and Predictive Molecular Biomarkers for Colorectal Cancer: Updates and Challenges , 2020, Cancers.

[88]  Jeffrey W. Clark,et al.  Serial ctDNA Monitoring to Predict Response to Systemic Therapy in Metastatic Gastrointestinal Cancers , 2020, Clinical Cancer Research.

[89]  Yue Zhang,et al.  Advances in immunotherapy for colorectal cancer: a review , 2020, Therapeutic advances in gastroenterology.

[90]  K. Ghaedi,et al.  Signaling pathways involved in colorectal cancer progression , 2019, Cell & Bioscience.

[91]  P. Laurent-Puig,et al.  Analysis of circulating tumour DNA (ctDNA) from patients enrolled in the IDEA-FRANCE phase III trial: Prognostic and predictive value for adjuvant treatment duration , 2019, Annals of Oncology.

[92]  A. Bardelli,et al.  How liquid biopsies can change clinical practice in oncology. , 2019, Annals of oncology : official journal of the European Society for Medical Oncology.

[93]  C. Supuran,et al.  Personalized Treatment Response Assessment for Rare Childhood Tumors Using Microcalorimetry–Exemplified by Use of Carbonic Anhydrase IX and Aquaporin 1 Inhibitors , 2019, International journal of molecular sciences.

[94]  Ga Ram Kim,et al.  Clinicopathological and biomolecular characteristics of stage IIB/IIC and stage IIIA colon cancer: Insight into the survival paradox , 2019, Journal of surgical oncology.

[95]  C. Chee,et al.  Making sense of adjuvant chemotherapy in colorectal cancer. , 2019, Journal of gastrointestinal oncology.

[96]  Edward S. Kim,et al.  The current state of molecular testing in the treatment of patients with solid tumors, 2019 , 2019, CA: a cancer journal for clinicians.

[97]  T. M. Murali,et al.  Benchmarking algorithms for gene regulatory network inference from single-cell transcriptomic data , 2019, Nature Methods.

[98]  Yongdong Feng,et al.  Cancer-associated fibroblasts enhance tumor-associated macrophages enrichment and suppress NK cells function in colorectal cancer , 2019, Cell Death & Disease.

[99]  S. Wong,et al.  Targeting immune cells for cancer therapy , 2019, Redox biology.

[100]  E. Pearce,et al.  Metabolic interventions in the immune response to cancer , 2019, Nature Reviews Immunology.

[101]  A. Bardelli,et al.  Plasma HER2 (ERBB2) Copy Number Predicts Response to HER2-targeted Therapy in Metastatic Colorectal Cancer , 2019, Clinical Cancer Research.

[102]  Huy Q. Dinh,et al.  Monocyte heterogeneity and functions in cancer , 2019, Journal of leukocyte biology.

[103]  Y. Zhang,et al.  Exosomes: biogenesis, biologic function and clinical potential , 2019, Cell & Bioscience.

[104]  Aimin Jiang,et al.  Dendritic Cells and CD8 T Cell Immunity in Tumor Microenvironment , 2018, Front. Immunol..

[105]  J. Fleshman,et al.  MicroRNAs as potential liquid biopsy biomarkers in colorectal cancer: A systematic review. , 2018, Biochimica et biophysica acta. Reviews on cancer.

[106]  Lu Wen,et al.  Single-cell multiomics sequencing and analyses of human colorectal cancer , 2018, Science.

[107]  Anubhav Srivastava,et al.  Discovery and Validation of Clinical Biomarkers of Cancer: A Review Combining Metabolomics and Proteomics , 2018, Proteomics.

[108]  Benjamin Werner,et al.  Longitudinal Liquid Biopsy and Mathematical Modeling of Clonal Evolution Forecast Time to Treatment Failure in the PROSPECT-C Phase II Colorectal Cancer Clinical Trial. , 2018, Cancer discovery.

[109]  P. Johnston,et al.  Transcriptional Subtyping and CD8 Immunohistochemistry Identifies Patients With Stage II and III Colorectal Cancer With Poor Prognosis Who Benefit From Adjuvant Chemotherapy , 2018, JCO precision oncology.

[110]  U. Testa,et al.  Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells , 2018, Medical sciences.

[111]  Hans Clevers,et al.  Intra-tumour diversification in colorectal cancer at the single-cell level , 2018, Nature.

[112]  C. Ishioka,et al.  Consensus molecular subtypes classification of colorectal cancer as a predictive factor for chemotherapeutic efficacy against metastatic colorectal cancer , 2018, Oncotarget.

[113]  Umberto Ricardi,et al.  Eighth Edition of the UICC Classification of Malignant Tumours: an overview of the changes in the pathological TNM classification criteria—What has changed and why? , 2018, Virchows Archiv.

[114]  M. Andreu,et al.  Colorectal cancer molecular classification using BRAF, KRAS, microsatellite instability and CIMP status: Prognostic implications and response to chemotherapy , 2018, PloS one.

[115]  L. Miller,et al.  Incorporating blood-based liquid biopsy information into cancer staging: time for a TNMB system? , 2018, Annals of oncology : official journal of the European Society for Medical Oncology.

[116]  N. Ellis,et al.  Colorectal Cancer Disparity in African Americans: Risk Factors and Carcinogenic Mechanisms. , 2017, The American journal of pathology.

[117]  A. van Oudenaarden,et al.  Single-cell sequencing reveals dissociation-induced gene expression in tissue subpopulations , 2017, Nature Methods.

[118]  Noam Shental,et al.  Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine , 2017, Science.

[119]  Xiaoling Li,et al.  MiR-590-5p, a density-sensitive microRNA, inhibits tumorigenesis by targeting YAP1 in colorectal cancer. , 2017, Cancer letters.

[120]  Fangfang Guo,et al.  Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy , 2017, Cell.

[121]  S. Kopetz,et al.  Platelets, circulating tumor cells, and the circulome , 2017, Cancer and Metastasis Reviews.

[122]  Elisa Ficarra,et al.  Selective analysis of cancer-cell intrinsic transcriptional traits defines novel clinically relevant subtypes of colorectal cancer , 2017, Nature Communications.

[123]  N. Hacohen,et al.  Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors , 2017, Science.

[124]  A. Bardelli,et al.  Integrating liquid biopsies into the management of cancer , 2017, Nature Reviews Clinical Oncology.

[125]  Alan U. Sabino,et al.  Stochastic model of contact inhibition and the proliferation of melanoma in situ , 2017, Scientific Reports.

[126]  Dorota Kwapisz,et al.  The first liquid biopsy test approved. Is it a new era of mutation testing for non-small cell lung cancer? , 2017, Annals of translational medicine.

[127]  J. Guinney,et al.  Consensus molecular subtypes and the evolution of precision medicine in colorectal cancer , 2017, Nature Reviews Cancer.

[128]  S. Pillai,et al.  B lymphocytes and cancer: a love-hate relationship. , 2016, Trends in cancer.

[129]  Rostyslav V Bubnov,et al.  Medicine in the early twenty-first century: paradigm and anticipation - EPMA position paper 2016 , 2016, EPMA Journal.

[130]  M. Sarfaraz,et al.  Temporal characterization of serum metabolite signatures in lung cancer patients undergoing treatment , 2016, Metabolomics.

[131]  D. Repana,et al.  Irinotecan chemotherapy combined with fluoropyrimidines versus irinotecan alone for overall survival and progression-free survival in patients with advanced and/or metastatic colorectal cancer. , 2016, The Cochrane database of systematic reviews.

[132]  W. Koh,et al.  Single-cell genome sequencing: current state of the science , 2016, Nature Reviews Genetics.

[133]  N. Pavlova,et al.  The Emerging Hallmarks of Cancer Metabolism. , 2016, Cell metabolism.

[134]  S. Turley,et al.  Immunological hallmarks of stromal cells in the tumour microenvironment , 2015, Nature Reviews Immunology.

[135]  Jeffrey S. Morris,et al.  The Consensus Molecular Subtypes of Colorectal Cancer , 2015, Nature Medicine.

[136]  J. Skibber,et al.  Overtreatment of young adults with colon cancer: more intense treatments with unmatched survival gains. , 2015, JAMA surgery.

[137]  Sashwati Roy,et al.  Laser capture microdissection: Big data from small samples. , 2015, Histology and histopathology.

[138]  M. Duffy Personalized treatment for patients with colorectal cancer: role of biomarkers. , 2015, Biomarkers in medicine.

[139]  C. Seretis,et al.  Hypercoagulation in colorectal cancer: What can platelet indices tell us? , 2015, Platelets.

[140]  E. Kohn,et al.  The MAPK pathway across different malignancies: A new perspective , 2014, Cancer.

[141]  G. Poston,et al.  TNM staging of colorectal cancer should be reconsidered by T stage weighting. , 2014, World journal of gastroenterology.

[142]  Olga Golubnitschaja,et al.  Predictive, Preventive and Personalised Medicine as the hardcore of ‘Horizon 2020’: EPMA position paper , 2014, EPMA Journal.

[143]  Caroline Mollevi,et al.  Specific Extracellular Matrix Remodeling Signature of Colon Hepatic Metastases , 2013, PloS one.

[144]  D. Frank Signal Transduction in Cancer , 2013 .

[145]  David M. Thomas,et al.  The Hippo pathway and human cancer , 2013, Nature Reviews Cancer.

[146]  K. Guan,et al.  The YAP and TAZ transcription co-activators: key downstream effectors of the mammalian Hippo pathway. , 2012, Seminars in cell & developmental biology.

[147]  Sven Diederichs,et al.  The hallmarks of cancer , 2012, RNA biology.

[148]  Johannes G. Reiter,et al.  The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers , 2012, Nature.

[149]  Sridhar Ramaswamy,et al.  Development and independent validation of a prognostic assay for stage II colon cancer using formalin-fixed paraffin-embedded tissue. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[150]  Davide Corà,et al.  A molecularly annotated platform of patient-derived xenografts ("xenopatients") identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. , 2011, Cancer discovery.

[151]  J. Gu [Precaution of over or under treatment for colorectal cancer]. , 2011, Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery.

[152]  S. Paik,et al.  Relationship between tumor gene expression and recurrence in four independent studies of patients with stage II/III colon cancer treated with surgery alone or surgery plus adjuvant fluorouracil plus leucovorin. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[153]  A. Bardelli,et al.  Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[154]  R. Goodwin,et al.  Overview of systemic therapy for colorectal cancer. , 2009, Clinics in colon and rectal surgery.

[155]  S. Milstien,et al.  Cross-talk between LPA1 and epidermal growth factor receptors mediates up-regulation of sphingosine kinase 1 to promote gastric cancer cell motility and invasion. , 2008, Cancer research.

[156]  G. Tortora,et al.  EGFR antagonists in cancer treatment. , 2008, The New England journal of medicine.

[157]  Marc Peeters,et al.  Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[158]  Boris Pasche,et al.  TGF-β signaling alterations and susceptibility to colorectal cancer , 2007 .

[159]  Silvia Benvenuti,et al.  Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. , 2007, Cancer research.

[160]  A. Lièvre,et al.  KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. , 2006, Cancer research.

[161]  Neal J Meropol,et al.  Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[162]  D. Kyriakou,et al.  Levels of Serum Cytokines and Acute Phase Proteins in Patients With Essential and Cancer‐Related Thrombocytosis , 2003, American journal of clinical oncology.

[163]  J. Maroun Capecitabine in the management of colorectal cancer , 2001, Expert review of anticancer therapy.

[164]  L. Sobin,et al.  TNM classification , 2001 .

[165]  N. Normanno,et al.  Epidermal growth factor-related peptides and their receptors in human malignancies. , 1995, Critical reviews in oncology/hematology.

[166]  I. Tsigelny,et al.  Genomic Landscape of Cell-Free DNA in Patients with Colorectal Cancer. , 2018, Cancer discovery.

[167]  B. Jung,et al.  Transforming Growth Factor β Superfamily Signaling in Development of Colorectal Cancer. , 2017, Gastroenterology.

[168]  Y. Fouad,et al.  Revisiting the hallmarks of cancer. , 2017, American journal of cancer research.

[169]  L. V. van't Veer,et al.  Gene expression signature to improve prognosis prediction of stage II and III colorectal cancer. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[170]  J. Downward Targeting RAS signalling pathways in cancer therapy , 2003, Nature Reviews Cancer.

[171]  Micheal Tadros,et al.  World Journal of Gastrointestinal Oncology Practical considerations for colorectal cancer screening in older adults , 2022 .

[172]  Ning Ma,et al.  Cuproptosis-related long non-coding RNAs model that effectively predicts prognosis in hepatocellular carcinoma , 2022, World Journal of Gastrointestinal Oncology.