Standard chemotherapy with cetuximab for treatment of colorectal cancer

Li, Xin Xiang; Liang, Lei; Huang, Li; Cai, San Jun

doi:10.3748/wjg.v21.i22.7022

Cited by 7 publications

(6 citation statements)

References 34 publications

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“…However, this benefit was mostly observed upon the mutation status of exon 2 in Kras. For patients with certain specific mutations in Kras, a greater sensitivity to anti-EGFR agents was found, when compared with other Kras mutations [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

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The impact of primary tumor location on efficacy of cetuximab in metastatic colorectal cancer patients with different Kras status: a systematic review and meta-analysis

Cao

et al. 2017

Oncotarget

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ObjectiveTo assess the prognostic role of primary tumor location along with Kras status in metastatic colorectal cancer (mCRCs) treated with cetuximab.Materials and MethodsDatabases of EMBASE, Pubmed, the Cochrane library, China National Knowledge Infrastructure and other databases from inception to July 2016 were searched. Randomized controlled trial (RCT) and/or retrospective studies of influence of primary tumor location on efficacy of cetuximab in patients with mCRC were identified. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), overall response rate (ORR) and disease control rate (DCR).ResultsTen studies including 2977 cases were finally included. The results of meta-analysis were in favor of cetuximab to patients with left-sided colorectal cancer in terms of OS (HR = 0.52, 95% CI: 0.40–0.66; p < 0.01), PFS (HR = 0.64, 95% CI: 0.58–0.70; p < 0.01), and ORR (OR = 2.17, 95% CI: 1.57–2.99; p < 0.01). Patients with right-sided CRC gained less benefit from cetuximab in terms of OS (HR = 1.89, 95% CI: 1.43–2.50; p < 0.01), compared with left-sided CRC. Regarding Kras status, left-sided mCRC with wild type Kras had better PFS (HR = 0.61, 95% CI: 0.51–0.74; p < 0.01) and OS (HR = 0.49, 95% CI: 0.35–0.69; p < 0.01) than right-sided cases when treated with cetuximab. We also found that cetuximab was both significantly effective in different treatment lines and regions when comparing by primary tumor locations (p < 0.01).ConclusionsmCRC Patients with left-sided, wild type Kras have a better prognosis than those with right-sided diseases when treated with cetuximab. The clinical application of cetuximab should be determined by the primary tumor location and molecular gene mutation status.

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Section: Discussionmentioning

confidence: 99%

“…Kars is one of the best known biomarker influencing the effectiveness of cetuximab [ 6 , 8 , 10 ]. Few months ago, Li Lin et al [ 8 ] used meta-analysis to investigate the cetuximab effectiveness in patients with different Kras status when combined with chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

The impact of primary tumor location on efficacy of cetuximab in metastatic colorectal cancer patients with different Kras status: a systematic review and meta-analysis

Cao

et al. 2017

Oncotarget

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“…Recall that cetuximab was first approved for colorectal cancer with EGFR expression by IHC in 2004 [ 105 ]. It was later found out that EGFR expression by IHC in colorectal cancer did not correlate with response to therapy, and subsequent investigation led to the identification of the KRAS mutation conferring resistance [ 106 ]. Further study revealed that the best responders were also wild-type for both KRAS and NRAS [ 107 ].…”

Section: Biomarker Development For Patients With Tumors Harboring Fgfmentioning

confidence: 99%

Inhibition of the fibroblast growth factor receptor (FGFR) pathway: the current landscape and barriers to clinical application

et al. 2016

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The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) is a tyrosine kinase signaling pathway that has a fundamental role in many biologic processes including embryonic development, tissue regeneration, and angiogenesis. Increasing evidence indicates that this pathway plays a critical role in oncogenesis via gene amplification, activating mutations, or translocation in tumors of various histologies. With multiplex sequencing technology, the detection of FGFR aberrations has become more common and is tied to cancer cell proliferation, resistance to anticancer therapies, and neoangiogenesis. Inhibition of FGFR signaling appears promising in preclinical studies, suggesting a pathway of clinical interest in the development of targeted therapy. Phase I trials have demonstrated a manageable toxicity profile. Currently, there are multiple FGFR inhibitors under study with many non-selective (multi-kinase) inhibitors demonstrating limited clinical responses. As we progress from the first generation of non-selective drugs to the second generation of selective FGFR inhibitors, it is clear that FGFR aberrations do not behave uniformly across cancer types; thus, a deeper understanding of biomarker strategies is undoubtedly warranted. This review aims to consolidate data from recent clinical trials with a focus on selective FGFR inhibitors. As Phase II clinical trials emerge, concentration on patient selection as it pertains to predicting response to therapy, feasible methods for overcoming toxicity, and the likelihood of combination therapies should be utilized. We will also discuss qualities that may be desirable in future generations of FGFR inhibitors, with the hope that overcoming these current barriers will expedite the availability of this novel class of medications.

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“…FDA-approved drugs, including temozolomide, gemcitabine, sunitinib, paclitaxel, and cetuximab, possess different mechanisms of antitumor action. Temozolomide, as an alkylating agent, promotes the initiation of apoptosis as a result of DNA damage during replication (Ohba and Hirose, 2016); sunitinib exhibits an anti-angiogenic effect by inhibiting tyrosine kinase receptors, in particular, the vascular endothelial growth factor receptor (Patel et al, 2016); gemcitabine, being a nucleotide analog bearing 2′-fluorine, blocks DNA synthesis (Song et al, 2016); cetuximab represents a monoclonal antibody that represses cell proliferation through the selective inhibition of the epidermal growth factor receptor (Li et al, 2015); and paclitaxel, belonging to the class of taxanes, exerts its cytostatic activity via suppression of the normal reorganization of microtubules during mitosis (Yardley, 2013). All these agents exhibit relatively high antitumor activity; however, the development of cancer cell resistance considerably reduces the efficacy of such therapy (Schlack et al, 2016).…”

Section: Combination Of Mirna-based Therapeutics and Chemotherapy To mentioning

confidence: 99%

Enhanced Inhibition of Tumorigenesis Using Combinations of miRNA-Targeted Therapeutics

Miroshnichenko

Patutina

2019

Front. Pharmacol.

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The search for effective strategies to inhibit tumorigenesis remains one of the most relevant scientific challenges. Among the most promising approaches is the direct modulation of the function of short non-coding RNAs, particularly miRNAs. These molecules are propitious targets for anticancer therapy, since they perform key regulatory roles in a variety of signaling cascades related to cell proliferation, apoptosis, migration, and invasion. The development of pathological states is often associated with deregulation of miRNA expression. The present review describes in detail the strategies aimed at modulating miRNA activity that invoke antisense oligonucleotide construction, such as small RNA zippers, miRNases (miRNA-targeted artificial ribonucleases), miRNA sponges, miRNA masks, anti-miRNA oligonucleotides, and synthetic miRNA mimics. The broad impact of developed miRNA-based therapeutics on the various events of tumorigenesis is also discussed. Above all, the focus of this review is to evaluate the results of the combined application of different miRNA-based agents and chemotherapeutic drugs for the inhibition of tumor development. Many studies indicate a considerable increase in the efficacy of anticancer therapy as a result of additive or synergistic effects of simultaneously applied therapies. Different drug combinations, such as a cocktail of antisense oligonucleotides or multipotent miRNA sponges directed at several oncogenic microRNAs belonging to the same/different miRNA families, a mixture of anti-miRNA oligonucleotides and cytostatic drugs, and a combination of synthetic miRNA mimics, have a more complex and profound effect on the various events of tumorigenesis as compared with treatment with a single miRNA-based agent or chemotherapeutic drug. These data provide strong evidence that the simultaneous application of several distinct strategies aimed at suppressing different cellular processes linked to tumorigenesis is a promising approach for cancer therapy.

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Standard chemotherapy with cetuximab for treatment of colorectal cancer

Cited by 7 publications

References 34 publications

The impact of primary tumor location on efficacy of cetuximab in metastatic colorectal cancer patients with different Kras status: a systematic review and meta-analysis

The impact of primary tumor location on efficacy of cetuximab in metastatic colorectal cancer patients with different Kras status: a systematic review and meta-analysis

Inhibition of the fibroblast growth factor receptor (FGFR) pathway: the current landscape and barriers to clinical application

Enhanced Inhibition of Tumorigenesis Using Combinations of miRNA-Targeted Therapeutics

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