Selection of Oral Therapeutics in China for the Treatment of Colorectal Cancer

2021 ◽  
Vol 22 (7) ◽  
Author(s):  
Jianxia Li ◽  
Yue Cai ◽  
Yanhong Deng
Keyword(s):  
Colorectal Cancer ◽  
Selection Of

scholarly journals AKT3 Expression in Mesenchymal Colorectal Cancer Cells Drives Growth and Is Associated with Epithelial-Mesenchymal Transition

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 801
Author(s):  
Joyce Y. Buikhuisen ◽  
Patricia M. Gomez Barila ◽  
Arezo Torang ◽  
Daniëlle Dekker ◽  
Joan H. de Jong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Surrogate Marker ◽  
High Expression ◽  
Mesenchymal Transition ◽  
High Propensity ◽  
Colorectal Cancer Cells ◽  
Epithelial Compartment ◽  
Selection Of

Colorectal cancer (CRC) is a heterogeneous disease that can currently be subdivided into four distinct consensus molecular subtypes (CMS) based on gene expression profiling. The CMS4 subtype is marked by high expression of mesenchymal genes and is associated with a worse overall prognosis compared to other CMSs. Importantly, this subtype responds poorly to the standard therapies currently used to treat CRC. We set out to explore what regulatory signalling networks underlie the CMS4 phenotype of cancer cells, specifically, by analysing which kinases were more highly expressed in this subtype compared to others. We found AKT3 to be expressed in the cancer cell epithelium of CRC specimens, patient derived xenograft (PDX) models and in (primary) cell cultures representing CMS4. Importantly, chemical inhibition or knockout of this gene hampers outgrowth of this subtype, as AKT3 controls expression of the cell cycle regulator p27KIP1. Furthermore, high AKT3 expression was associated with high expression of epithelial-mesenchymal transition (EMT) genes, and this observation could be expanded to cell lines representing other carcinoma types. More importantly, this association allowed for the identification of CRC patients with a high propensity to metastasise and an associated poor prognosis. High AKT3 expression in the tumour epithelial compartment may thus be used as a surrogate marker for EMT and may allow for a selection of CRC patients that could benefit from AKT3-targeted therapy.

scholarly journals Bevacizumab in neoadjuvant treatment of patients with liver metastases from colorectal carcinoma

2010 ◽  
Vol 18 (3) ◽  
pp. 75-78
Author(s):  
Ivan Nikolic ◽  
Svetlana Pavin ◽  
Biljana Kukic ◽  
Bogdan Bogdanovic ◽  
Miroslav Ilic ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Neoadjuvant Treatment ◽  
Hepatic Metastases ◽  
Response Rates ◽  
Control Group ◽  
Significant Difference ◽  
Experimental Group ◽  
Selection Of Patients ◽  
Selection Of

Background: Liver metastases are the leading cause of death in patients with colorectal cancer. Despite advances in chemotherapy, surgical resection of hepatic metastases is still considered the only curative options. However, the majority of patients have inoperable disease at presentation. Perioperative chemotherapy is the most successful way for improved selection of patients for resection. The aim of the study was to demonstrate if and to what extent does bevacizumab, introduced in chemotherapy, increase response rates, and development of liver metastases. Methods: Our study included 50 patients who were divided in two groups. The experimental group included patients who were treated with bevacizumab plus chemotherapy, and the control group included patients who were treated with chemotherapy only. Results: The comparison showed that the patients who were treated with bevacizumab became candidates for resection of liver metastases in higher percentage (85%:52%). In addition, distribution of patients regarding the development of metastases resulted in statistically significant difference. Ratio between the patients with good response from the experimental and the control group was 67%:39%. Ratio of patients with stable disease was 26%:48%, and of patients with progressive disease, it was 7%:3%. The estimate of margin after resection was statistically insignificant. Conclusion: Bevacizumab in combination with chemotherapy in therapy of liver metastases from primary colorectal cancer improves and increases response rates and development of liver metastases.

scholarly journals Biomarker Use in Colorectal Cancer Therapy

2011 ◽  
Vol 9 (11) ◽  
pp. 1293-1302 ◽  
Author(s):  
Robin K. Kelley ◽  
Grace Wang ◽  
Alan P. Venook
Keyword(s):  
Colorectal Cancer ◽  
Clinical Management ◽  
Mutational Analysis ◽  
Colorectal Cancers ◽  
Repair Protein ◽  
Established Role ◽  
Case Based ◽  
Mismatch Repair Protein ◽  
Selection Of ◽  
Novel Therapeutic

Biomarkers reflective of the molecular and genetic heterogeneity in colorectal cancers now guide certain aspects of clinical management and offer great potential for enrichment, stratification, and identification of novel therapeutic targets in drug development. Using case-based examples, this article reviews biomarkers that have an established role in the clinical management of colorectal cancer: mismatch repair protein testing and KRAS and BRAF mutational analysis. A selection of biomarkers undergoing validation for future clinical application is presented, and the dynamic and challenging interface between biomarkers in research and clinical practice is discussed.

scholarly journals Combining Correlated Outcomes and Surrogate Endpoints in a Network Meta-Analysis of Colorectal Cancer Treatments

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2663
Author(s):  
Tung Hoang ◽  
Jeongseon Kim
Keyword(s):  
Colorectal Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Cancer Treatments ◽  
Free Survival ◽  
Hazard Ratios ◽  
Credible Intervals ◽  
Grade 3 ◽  
Selection Of

This study aimed to investigate the efficacy and safety of systemic therapies in the treatment of unresectable advanced or metastatic colorectal cancer. Predicted hazard ratios (HRs) and their 95% credible intervals (CrIs) for overall survival (OS) were calculated from the odds ratio (OR) for the overall response rate and/or HR for progression-free survival using multivariate random effects (MVRE) models. We performed a network meta-analysis (NMA) of 49 articles to compare the efficacy and safety of FOLFOX/FOLFIRI±bevacizumab (Bmab)/cetuximab (Cmab)/panitumumab (Pmab), and FOLFOXIRI/CAPEOX±Bmab. The NMA showed significant OS improvement with FOLFOX, FOLFOX+Cmab, and FOLFIRI+Cmab compared with that of FOLFIRI (HR = 0.84, 95% CrI = 0.73–0.98; HR = 0.76, 95% CrI = 0.62–0.94; HR = 0.80, 95% CrI = 0.66–0.96, respectively), as well as with FOLFOX+Cmab and FOLFIRI+Cmab compared with that of FOLFOXIRI (HR = 0.69, 95% CrI = 0.51–0.94 and HR = 0.73, 95% CrI = 0.54–0.97, respectively). The odds of adverse events grade ≥3 were significantly higher for FOLFOX+Cmab vs. FOLFIRI+Bmab (OR = 2.34, 95% CrI = 1.01–4.66). Higher odds of events were observed for FOLFIRI+Pmab in comparison with FOLFIRI (OR = 2.16, 95% CrI = 1.09–3.84) and FOLFIRI+Bmab (OR = 3.14, 95% CrI = 1.51–5.89). FOLFOX+Cmab and FOLFIRI+Bmab showed high probabilities of being first- and second-line treatments in terms of the efficacy and safety, respectively. The findings of the efficacy and safety comparisons may support the selection of appropriate treatments in clinical practice. PROSPERO registration: CRD42020153640.

scholarly journals Genomic Alterations and Their Implications on Survival in Nonmetastatic Colorectal Cancer: Status Quo and Future Perspectives

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2001 ◽  
Author(s):  
Reetu Mukherji ◽  
John Marshall ◽  
Andreas Seeber
Keyword(s):  
Colorectal Cancer ◽  
Current Knowledge ◽  
Locally Advanced ◽  
Tumor Resection ◽  
Daily Routine ◽  
Precision Oncology ◽  
Genomic Alterations ◽  
Future Challenges ◽  
The Status ◽  
Selection Of

The selection of treatment according to genomic alterations is a standard approach in metastatic colorectal cancer but is only starting to have an impact in the earlier stages of the disease. The status of genes like KRAS, BRAF, and MMR has substantial survival implications, and concerted research efforts have revolutionized treatment towards precision oncology. In contrast, a genomic-based approach has not changed the adjuvant setting after curative tumor-resection in the daily routine so far. This review focuses on the current knowledge regarding prognostic and predictive genomic biomarkers in patients with locally advanced nonmetastasized colorectal cancer. Furthermore, we provide an outlook on future challenges for a personalized adjuvant treatment approach in patients with colorectal cancer.

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