Prospective Biomarker Study in Advanced RAS Wild-Type Colorectal Cancer: POSIBA Trial (GEMCAD 10-02)

García-Albéniz, Xabier; Alonso, Vicente; Escudero, P.; Méndez, Miguel; Gállego, Javier; Rodríguez, José Ramón; Salud, A.; Fernández-Plana, Julen; Manzano, Hermini; Zanui, Montserrat; Falcó, E.; Feliú, Jaime; Gil, M. G.; Fernández-Martos, Carlos; Bohn, Uriel; Alonso, C. Llano; Calderero, V.; Rojo, Federico; Cuatrecasas, Míriam; Maurel, Joan

doi:10.1634/theoncologist.2018-0728

Cited by 9 publications

(11 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unfortunately, they are only effective in a small percentage of patients [5,6,7] due to primary or secondary/acquired resistance to this kind of therapy. Notably, even the patients that initially respond to the EGFR blockade therapy usually develop secondary resistance over time by a number of causes [8,9,10,11,12,13,14]. Alterations in RAS, among other genes, represents the main mechanisms of this resistance [11,12].…”

Section: Introductionmentioning

confidence: 99%

“…Despite these efforts, additional mechanisms of resistance to EGFR blockade are thought to be present in CRC and little is known about the determinants of sensitivity to this therapy [13,14,15,16]. Among them, it is important to mention Raf , PI3K , and MAP2K1 mutations, ERBB2 and MET amplification, low EGFR gene copy number, IGF1 overexpression, PTEN loss, over-activation of STAT3 by JAK, or mediated by nuclear PKM2 [5,6,9,10]. The latest evidences strongly suggest that complex molecular alterations coupled with changes in the tumor microenvironment may substantially contribute to the clinical efficacy of EGFR antagonists, even in CRC that are both KRAS and NRAS wild type [5,6,7,8,9,10,14].…”

Section: Introductionmentioning

confidence: 99%

“…Among them, it is important to mention Raf , PI3K , and MAP2K1 mutations, ERBB2 and MET amplification, low EGFR gene copy number, IGF1 overexpression, PTEN loss, over-activation of STAT3 by JAK, or mediated by nuclear PKM2 [5,6,9,10]. The latest evidences strongly suggest that complex molecular alterations coupled with changes in the tumor microenvironment may substantially contribute to the clinical efficacy of EGFR antagonists, even in CRC that are both KRAS and NRAS wild type [5,6,7,8,9,10,14]. In this review, we first discuss the mechanisms by which EGFR secondary alterations induce compensatory functions against the inhibition of EGFR.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Immune Resistance and EGFR Antagonists in Colorectal Cancer

Giordano

Remo²,

Porrás

et al. 2019

Cancers

View full text Add to dashboard Cite

: Targeting the epidermal growth factor receptor (EGFR) either alone or in combination with chemotherapy in patients with RAS wild type metastatic colorectal cancer (mCRC) has revolutionized the treatment of CRC, but with less results than initially envisaged. In recent years, the discovery of multiple pathways leading to the escape from anti-EGFR therapy has revealed an enormous complexity and heterogeneity of human CRC due to the intrinsic genomic instability and immune/cancer cell interaction. Therefore, understanding the mechanistic basis of acquired resistance to targeted therapies represents a major challenge to improve the clinical outcomes of patients with CRC. The latest findings strongly suggest that complex molecular alterations coupled with changes of the immune tumor microenvironment may substantially contribute to the clinical efficacy of EGFR antagonist. In this review, we discuss the most recent findings that contribute to both primary and acquired anti-EGFR therapy resistance. In addition, we analyze how strategies aiming to enhance the favorable effects in the tumor microenvironment may contribute to overcome resistance to EGFR therapies.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Immune Resistance and EGFR Antagonists in Colorectal Cancer

Giordano

Remo²,

Porrás

et al. 2019

Cancers

View full text Add to dashboard Cite

show abstract

“…It's being increasingly recognized that immune condition plays a decisive role in the genesis and progressiveness of malignant tumors. The host's immune dysfunction signi cantly impairs body's anti-tumor surveillance, along with ill-transformed cells' immune-avoiding mechanism acquired from the accumulation of gene mutation, is a vital step towards tumor development [11][12][13] . The most wildly recognized prognostic biomarkers for immune therapy were programmed death ligand (PD-1), tumor mutation burden (TMB) and microsatellite instability/ mismatch repair de ciency (dMMR) 14 .…”

Section: Introductionmentioning

confidence: 99%

Identification of an immune-related gene signature to improve prognosis prediction of colorectal cancer patients

Dai

Yao

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Despite recent advance in immune therapy, great heterogeneity exists in colorectal cancer (CRC) patients’ outcome. In this study, we aimed to analyze the Immune-related gene (IRG) expression profiles from two independent public databases and develop an effective signature to forecast patients’ prognosis.Method: IRGs were collected from The Cancer Genome Atlas (TCGA) database to identify a prognostic genes signature, which was verified in Gene Expression Omnibus (GEO) database. Gene function enrichment and immune cell infiltration analyses were conducted. A prognostic nomogram was built incorporating the IRG signature with clinical risk factors.Results: The training and test datasets had 487 and 579 patients, respectively. A prognostic six-gene-signature (CCL22, LIMK1, MAPKAPK3, FLOT1, GPRC5B and IL20RB) was developed through feature selection, and yielded incredible differentiation between low and high-risk group in the training set (P < 0.001), which was confirmed in the test group (P < 0.001). The signature outperformed tumor staging regarding survival prediction. Go and KEGG functional annotation analysis suggested the signature were significantly enriched in metabolic process and regulation of immunity (P<0.05). When combined with clinical risk factors, the model showed robust prediction capability.Conclusion: The immune-related six-gene signature is a reliable prognostic indicator for CRC patients and could bring insight for personalized cancer management.

show abstract

“…However, they are only effective in a small percentage of patients [11][12][13] due to either intrinsic or acquired resistance to this type of therapy. Unfortunately, even the patients that initially respond to EGFR antagonists usually acquired resistance over time [14][15][16]. Taken together, these findings necessitate a change in treatment and prediction approaches.…”

Section: Introductionmentioning

confidence: 99%

Actionable Potentials of Less Frequently Mutated Genes in Colorectal Cancer and Their Roles in Precision Medicine

et al. 2020

View full text Add to dashboard Cite

Global statistics have placed colorectal cancer (CRC) as the third most frequently diagnosed cancer and the fourth principal cause of cancer-related deaths worldwide. Improving survival for CRC is as important as early detection. Personalized medicine is important in maximizing an individual’s treatment success and minimizing the risk of adverse reactions. Approaches in achieving personalized therapy in CRC have included analyses of specific genes with its clinical implications. Tumour genotyping via next-generation sequencing has become a standard practice to guide clinicians into predicting tumor behaviour, disease prognosis, and treatment response. Nevertheless, better prognostic markers are necessary to further stratify patients for personalized treatment plans. The discovery of new markers remains indispensable in providing the most effective chemotherapy in order to improve the outcomes of treatment and survival in CRC patients. This review aims to compile and discuss newly discovered, less frequently mutated genes in CRC. We also discuss how these mutations are being used to assist therapeutic decisions and their potential prospective clinical utilities. In addition, we will summarize the importance of profiling the large genomic rearrangements, gene amplification, and large deletions and how these alterations may assist in determining the best treatment option for CRC patients.

show abstract

Prospective Biomarker Study in Advanced RAS Wild-Type Colorectal Cancer: POSIBA Trial (GEMCAD 10-02)

Abstract: This articles compares the capacity of several biomarkers (BRAF mutation, PIK3CA mutation/PTEN loss and DP phenotype) to predict 12‐month progression‐free survival and compares it with that of clinical variables

Cited by 9 publications

References 29 publications

Immune Resistance and EGFR Antagonists in Colorectal Cancer

Immune Resistance and EGFR Antagonists in Colorectal Cancer

Identification of an immune-related gene signature to improve prognosis prediction of colorectal cancer patients

Actionable Potentials of Less Frequently Mutated Genes in Colorectal Cancer and Their Roles in Precision Medicine

Contact Info

Product

Resources

About