Precision medicine in colorectal cancer: the molecular profile alters treatment strategies

Tran, Nguyen H.; Cavalcante, Ludmila L.; Lubner, Sam Joseph; Mulkerin, Daniel; LoConte, Noelle K.; Clipson, Linda; Matkowskyj, Kristina A.; Deming, Dustin A.

doi:10.1177/1758834015591952

Cited by 71 publications

(42 citation statements)

References 45 publications

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“…The treatment paradigm for CRLM is rapidly shifting to a more personalized approach so as to execute precision medicine [31]. In a large, non-randomized study, patients exhibiting factors associated with a high risk of recurrence gained more benefit from adjuvant therapy than those with factors suggesting a low risk of recurrence [32].…”

Section: Discussionmentioning

confidence: 99%

The role of neoadjuvant chemotherapy for resectable colorectal liver metastases: a systematic review and meta-analysis

et al. 2016

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Neoadjuvant chemotherapy is being increasingly accepted as an effective treatment of resectable colorectal liver metastases (CRLM), but it may also damage the hepatic parenchyma. We performed a meta-analysis to compare the outcomes of patients who received neoadjuvant chemotherapy (NEO) prior to hepatic resection with hepatic resection without neoadjuvant chemotherapy (SG). Eligible trials were identified from Embase, PubMed, the Web of Science and the Cochrane library. Hazard ratios (HRs) with a 95% confidence intervals (CIs) were used to measure the pooled effect using a random-effects model. Statistical heterogeneity was detected by I2 test. Sensitivity analyses and publication bias were also assessed. The study outcomes included 3-year, 5-year disease-free and overall survival rate, respectively. Eighteen studies involving 6,254 patients were included. The pooled HRs for 5-year DFS and 5-year OS for NEO in the included studies calculated using the random-effects model were 1.38 (95 % CI; 1.26-1.51, p=0.00; I2=9.6%, p=0.36) and 1.19 (95% CI: 1.02-1.38; p=0.03; I2=49.2%, p=0.03), respectively. For CRLM patients with factors indicating a high risk of recurrence, the pooled HR for 5-year OS of NEO in the included studies calculated using the random-effects model was 0.69 (95% CI: 0.55-0.87; p=0.00; I2=0.0%, p=0.48). These results suggest neoadjuvant chemotherapy improved survival of patients with initially resectable CRLM and a high risk of disease recurrence.

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Section: Discussionmentioning

confidence: 99%

The role of neoadjuvant chemotherapy for resectable colorectal liver metastases: a systematic review and meta-analysis

et al. 2016

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“…However, subsequent analyses has suggested that CRC patients with KRAS G13 mutations benefit from anti-EGFR therapy (Tejpar et al, 2012). This issue continues to evolve (Van Cutsem et al, 2015) because the National Comprehensive Cancer Network recommendation now indicates that CRC patients with any KRAS or NRAS mutation, including those of Q61 and A146, will not benefit from anti-EGFR therapy (Tran et al, 2015).…”

Section: Ras Mutation Hotspots -Structural Biological and Functionalmentioning

confidence: 99%

RAS isoforms and mutations in cancer at a glance

Hobbs

Der

Rossman

2016

Journal of Cell Science

779

709

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RAS proteins (KRAS4A, KRAS4B, NRAS and HRAS) function as GDP-GTP-regulated binary on-off switches, which regulate cytoplasmic signaling networks that control diverse normal cellular processes. Gain-of-function missense mutations in RAS genes are found in ∼25% of human cancers, prompting interest in identifying anti-RAS therapeutic strategies for cancer treatment. However, despite more than three decades of intense effort, no anti-RAS therapies have reached clinical application. Contributing to this failure has been an underestimation of the complexities of RAS. First, there is now appreciation that the four human RAS proteins are not functionally identical. Second, with >130 different missense mutations found in cancer, there is an emerging view that there are mutation-specific consequences on RAS structure, biochemistry and biology, and mutation-selective therapeutic strategies are needed. In this Cell Science at a Glance article and accompanying poster, we provide a snapshot of the differences between RAS isoforms and mutations, as well as the current status of anti-RAS drug-discovery efforts.

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“…Depending upon the stage, the treatment of colon cancer involves multiple modalities, including surgery, radiotherapy, interventional radiology approaches and systemic chemotherapy. Although targeted therapy drugs for colon cancer have been introduced (2), such as bevacizumab, cetuximab and panitumumab, the prognosis remains unsatisfactory (3,4). Thus, there is still a great clinical need to develop drugs for colon cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol inactivates PI3K/Akt signaling through upregulating BMP7 in human colon cancer cells

et al. 2017

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Abstract. Colon cancer is common worldwide and accounts for the significant cancer related morbidity and mortality in patients. Although extensive advancement has been made in colon cancer treatment and diagnosis in the last decades, there is still a giant gap between the clinical expectation. It has been reported that resveratrol (Res) may be a potential candidate for cancer treatment. However, the specific mechanism underlying this activity remains unclear. In this study, we investigated the anticancer activity of Res in human colon cancer cells, and unveiled the possible mechanism for this effect. With cell viability, flow cytometry, PCR and western blot analysis, we demonstrated the efficacious anticancer activity of Res in HCT116 cells. Mechanically, we found that Res greatly upregulates BMP7 in HCT116 cells. Exogenous BMP7 enhances the anticancer effect of Res in HCT116 cells, which was almost reversed by the BMP7 specific antibody. Res does not activate the BMPs/Smads signaling, but decreases the phosphorylation of Akt1/2/3 substantially in HCT116 cells. Exogenous BMP7 enhances the inhibitory effect of Res on the phosphorylation of Akt1/2/3, while BMP7 immunodepletion reverses this effect notably. Res markedly decreases the phosphorylation of PTEN, which can be enhanced by exogenous BMP7 but partly reversed by the BMP7 antibody. Our findings suggested that Res may be a promising candidate for colon cancer treatment, and the anticancer activity may be mediated by inactivating PI3K/Akt signaling through upregulating BMP7 to decrease, at least, the phosphorylation of

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Precision medicine in colorectal cancer: the molecular profile alters treatment strategies

Cited by 71 publications

References 45 publications

The role of neoadjuvant chemotherapy for resectable colorectal liver metastases: a systematic review and meta-analysis

The role of neoadjuvant chemotherapy for resectable colorectal liver metastases: a systematic review and meta-analysis

RAS isoforms and mutations in cancer at a glance

Resveratrol inactivates PI3K/Akt signaling through upregulating BMP7 in human colon cancer cells

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