Comprehensive review of targeted therapy for colorectal cancer

Xie, Yuanhong; Chen, Yingxuan; Fang, Jing‐Yuan

doi:10.1038/s41392-020-0116-z

Cited by 917 publications

(663 citation statements)

References 497 publications

(552 reference statements)

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“…Colorectal cancer (CRC) is globally the third most commonly diagnosed and second leading cause of cancer-related deaths for both sexes [ 1 ]. Recent improvements in survival are associated with both earlier disease detection and the development of personalized tumor biology-based therapies [ 1 , 2 ]. The main factor in cancer management however is still the traditional tumor-node-metastasis (TNM) staging system.…”

Section: Introductionmentioning

confidence: 99%

“…Currently, only a few molecular markers have been implemented for the management of CRC although these have mainly been for therapy stratification such as testing for activating KRAS , NRAS and BRAF gene mutations as exclusion criteria for the use of EGFR-targeted therapies in metastatic CRC (mCRC) [ 2 ]. Although RAS and BRAF mutations are considered to be poor prognostic factors [ 7 ], outside of targeted therapies, they are not used for outcome predictions in routine CRC diagnostics.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Immuno-Interface Score to Predict Outcome in Colorectal Cancer Independent of Microsatellite Instability Status

Nestarenkaite

Fadhil

Rasmusson

et al. 2020

Cancers

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Tumor-associated immune cells have been shown to predict patient outcome in colorectal (CRC) and other cancers. Spatial digital image analysis-based cell quantification increases the informative power delivered by tumor microenvironment features and leads to new prognostic scoring systems. In this study we evaluated the intratumoral density of immunohistochemically stained CD8, CD20 and CD68 cells in 87 cases of CRC (48 were microsatellite stable, MSS, and 39 had microsatellite instability, MSI) in both the intratumoral tumor tissue and within the tumor-stroma interface zone (IZ) which was extracted by a previously developed unbiased hexagonal grid analytics method. Indicators of immune-cell gradients across the extracted IZ were computed and explored along with absolute cell densities, clinicopathological and molecular data, including gene mutation (BRAF, KRAS, PIK3CA) and MSI status. Multiple regression modeling identified (p < 0.0001) three independent prognostic factors: CD8+ and CD20+ Immunogradient indicators, that reflect cell migration towards the tumor, were associated with improved patient survival, while the infiltrative tumor growth pattern was linked to worse patient outcome. These features were combined into CD8-CD20 Immunogradient and immuno-interface scores which outperformed both tumor-node-metastasis (TNM) staging and molecular characteristics, and importantly, revealed high prognostic value both in MSS and MSI CRCs.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immuno-Interface Score to Predict Outcome in Colorectal Cancer Independent of Microsatellite Instability Status

Nestarenkaite

Fadhil

Rasmusson

et al. 2020

Cancers

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show abstract

“…In vivo PET with radiolabeled mAb can help to study the kinetics of mAb delivery and localization in both animals and humans [ 61 ]. Cetuximab competitively targeting the ligand-binding site of epidermal growth factor receptor (EGFR) was the first mAb approved by the FDA for the treatment of EGFR-expressing, metastatic colorectal carcinoma [ 62 ]. As shown in Fig.…”

Section: Assessment Of Biological Functionsmentioning

confidence: 99%

Recent progress in the molecular imaging of therapeutic monoclonal antibodies

Zeng

Qian

2020

Journal of Pharmaceutical Analysis

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Therapeutic monoclonal antibodies have become one of the central components of the healthcare system and continuous efforts are made to bring innovative antibody therapeutics to patients in need. It is equally critical to acquire sufficient knowledge of their molecular structure and biological functions to ensure the efficacy and safety by incorporating new detection approaches since new challenges like individual differences and resistance are presented. Conventional techniques for determining antibody disposition including plasma drug concentration measurements using LC-MS or ELISA, and tissue distribution using immunohistochemistry and immunofluorescence are now complemented with molecular imaging modalities like positron emission tomography and near-infrared fluorescence imaging to obtain more dynamic information, while methods for characterization of antibody’s interaction with the target antigen as well as visualization of its cellular and intercellular behavior are still under development. Recent progress in detecting therapeutic antibodies, in particular, the development of methods suitable for illustrating the molecular dynamics, is described here.

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“…Selected peptides were primarily chosen from discovery analyses performed on a cohort of CRC samples; this list was then supplemented with additional peptides from pathways of interest. These sites include EGFR and T cell signaling pathway peptides, as EGFR inhibitors and immune checkpoint blockade (ICB) are two common therapies within CRC and other cancer types (26,27). Selected pTyr sites primarily cover two branches of the kinome: tyrosine kinases and CMGC kinases (cyclin-dependent kinases (CDK), mitogen-activated protein (MAP) kinases, glycogen synthase kinases, and CDKlike kinases), which include tyrosine kinase signaling pathways relevant in cancer (7).…”

Section: Targeted Ptyr Proteomic Workflow Utilizing Internal Standardmentioning

confidence: 99%

High-density, targeted monitoring of tyrosine phosphorylation reveals activated signaling networks in human tumors

Stopfer

Flower

Gajadhar

et al. 2020

Preprint

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A targeted, mass spectrometry-based method, termed "SureQuant pTyr," enables highly sensitive and reproducible profiling of tyrosine phosphorylation levels in human colorectal tumors and reveals dysregulated signaling networks for enhanced tumor characterization and biomarker identification. 2 Abstract:Tyrosine phosphorylation (pTyr) plays a pivotal role in signal transduction and is commonly dysregulated in cancer. As a result, profiling tumor pTyr levels may reveal therapeutic insights critical to combating disease. Existing discovery and targeted mass spectrometry-based methods used to monitor pTyr networks involve a tradeoff between broad coverage of the pTyr network, reproducibility in target identification across analyses, and accurate quantification. To address these limitations, we developed a targeted approach, termed "SureQuant pTyr," coupling low input pTyr enrichment with a panel of isotopically labeled, tyrosine phosphorylated internal standard (IS) peptides. Using internal standard guided acquisition, the real-time detection of IS peptides during the analysis initiates the sensitive and selective quantitation of endogenous pTyr targets. This framework allows for reliable quantification of several hundred commonly dysregulated pTyr targets with high quantitative accuracy, enhances target detection success rates, and improves the robustness and usability of targeted acquisition. We establish the clinical applicability of SureQuant pTyr by profiling pTyr signaling levels in human colorectal tumors using minimal sample input, characterizing patient specific oncogenic driving mechanisms. While in some cases pTyr profiles align with previously reported proteomic, genomic, and transcriptomic molecular characterizations, we highlight instances of new insights gained using pTyr characterization and emphasize the complementary nature of pTyr measurements with traditional biomarkers for improving patient stratification and identifying therapeutic targets. The turn-key nature of this approach opens the door to rapid and reproducible pTyr profiling in research and clinical settings alike and enable pTyr-based measurements for applications in precision medicine.

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Comprehensive review of targeted therapy for colorectal cancer

Cited by 917 publications

References 497 publications

Immuno-Interface Score to Predict Outcome in Colorectal Cancer Independent of Microsatellite Instability Status

Immuno-Interface Score to Predict Outcome in Colorectal Cancer Independent of Microsatellite Instability Status

Recent progress in the molecular imaging of therapeutic monoclonal antibodies

High-density, targeted monitoring of tyrosine phosphorylation reveals activated signaling networks in human tumors

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