Metastatic colorectal cancer-prolonging overall survival with targeted therapies

Dattatreya, Satya

doi:10.4103/2278-330x.114152

Cited by 27 publications

(20 citation statements)

References 34 publications

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“…Progress in multidisciplinary treatment had greatly improved the outcomes of patients diagnosed with early stage of the disease, but the outcomes of those diagnosed with advanced stage of the disease remains still very poor (Dattatreya, 2013). Better prognosis of colorectal cancer patients depends on early detection of the disease.…”

Section: Discussionmentioning

confidence: 99%

“…Despite recent progresses in diagnosis of colorectal cancer and in its management (Dattatreya, 2013;Price et al, 2013;Khoshbaten et al, 2014), the number of mortalities is still progressively increasing every year. Many patients with localized colorectal cancer have micrometastatic disease are usually miss diagnosed, which results in disease recurrence and mortality several years after diagnosis (Noura et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Periostin as a promising target of therapeutical intervention for colorectal cancer

Song

Shi

et al. 2014

Bangladesh J Pharmacol

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Periostin as a promising target of therapeutical intervention for colorectal cancer

Song

Shi

et al. 2014

Bangladesh J Pharmacol

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“…Although adjuvant chemotherapies have initially a high response rate, entire populations of patients do not benefit from treatment [14,15]. Therefore, personalized medicine gets more and more essential [16,17], comprising new classes of therapeutic agents like small molecules [18][19][20] and therapeutic monoclonal antibodies [21][22][23]. Most of these drugs are directed against specific cellular and molecular targets of signaling pathways, such as key receptors, or signaling proteins, which are elevated in certain tumors [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Precision Cut Cancer Tissue Slices in Anti-Cancer Drug Testing

Unger¹,

Bentz²,

Krüger³

et al. 2015

J Mol Pathophysiol

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Background: To meet the urgent need to predict individual drug responses of patients and thus support drug development, better preclinical models of solid tumors are inevitable. Here, a newly developed precision cut cancer tissue slice culture is presented and its use in drug testing was evaluated. Methods: Efficacy of therapeutic compounds from different classes, i.e. Staurosporine, IRESSATM, and Herceptin® was tested within the drug testing platform using fresh precision cut cancer slices from human colon, lung, or breast tumor tissues. The stability and significance of the model were evaluated on the level of gene expression, by antibody diffusion assays, and drug responses were detected by immunohistochemical staining, Meso Scale Discovery (Akt, pAkt) analysis, Western blotting (pAkt, pMAPK), viability (ATP) and apoptosis assays (Caspase-3/7). Results: We obtained sufficient numbers of tissue slices from cancer specimens to be able to perform a wide range of experiments for each individual tumor. In our culture system, cells remained viable and proliferated for at least 4 days within their tissue environment. Viability of tissue slices decreased significantly due to therapeutic treatment in a dose-dependent manner. Gene expression varied remarkably in primary cultivated cells and HT-29 cells in comparison to cultivated tumor slices, which closely represent freshly isolated tumor tissue. An Alexa Fluor 488-labelled antibody showed diffusion in deeper cell layers and the ability of the system to evaluate effects of antibody therapy. Sustained viability of the precision cut cancer tissue slices over 72h enabled to test different drugs. Staurosporine, Iressa TM , and Herceptin® showed a dose-dependent reduction of viability and downstream signaling pathways like Akt and MAPK kinase phosphorylation in EGFR-or Her-2-positive Caco-2 or BT-474 cells or tissue slices, respectively. No effect was seen in EGFR-or Her-2-negative cells and tissues. Conclusions: We showed that this preclinical model is applicable to examine the effects of various anti-cancer compounds like cytotoxic chemotherapeutic drugs as well as targeted therapeutics. It may therefore have significant impact on drug development and patient selection for initial clinical trials.

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“…Although the CRC mortality rate has been dramatically decreased owing to significant improvement in early diagnostics, surgical techniques, and chemotherapy, the disease‐free survival rate for patients with advanced‐stage CRC remains low. Because invasion and proliferation are the two most important characteristics of CRC contributing to a poor prognosis , it is imperative to identify novel therapeutic targets and develop more effective treatment strategies for patients with CRC.…”

Section: Introductionmentioning

confidence: 99%

High expression of DJ‐1 promotes growth and invasion via the PTEN‐AKT pathway and predicts a poor prognosis in colorectal cancer

et al. 2018

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Cancer cell invasion and unlimited proliferation are key factors in patients with colorectal cancer (CRC). Increased protein deglycase DJ‐1 in cancer cells is known to promote tumor growth; however, its role in CRC progression is not well defined. In this study, we investigated 100 CRC patients with disease stages I–IV to determine whether DJ‐1 could serve as a prognostic biomarker in CRC. These results showed that DJ‐1 expression in CRC tissues was higher than that in normal colon tissues and was associated with the (Tumor Node Metastasis) TNM stage. CRC patients with low DJ‐1 expression had a longer overall survival than those with high expression, and multivariate and univariate analyses indicated that DJ‐1 expression was an independent prognostic factor for overall survival in CRC. Furthermore, DJ‐1 overexpression in two colon cancer cell lines, HCT116 and SW480, activated protein kinase AKT and downregulated tumor suppressor PTEN, whereas DJ‐1 knockdown upregulated PTEN expression and effectively suppressed CRC cell invasion and proliferation both in vitro and in vivo, revealing a mechanism underlying DJ‐1 pro‐oncogenic activity in CRC. Treatment of MK2206, the specific AKT inhibitor, significantly decreased DJ‐1‐mediated cell proliferation and mobility in vitro. Taken together, these results suggest that DJ‐1 may be a novel prognostic biomarker and potential therapeutic target in human CRC.

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Metastatic colorectal cancer-prolonging overall survival with targeted therapies

Cited by 27 publications

References 34 publications

Periostin as a promising target of therapeutical intervention for colorectal cancer

Periostin as a promising target of therapeutical intervention for colorectal cancer

Precision Cut Cancer Tissue Slices in Anti-Cancer Drug Testing

High expression of DJ‐1 promotes growth and invasion via the PTEN‐AKT pathway and predicts a poor prognosis in colorectal cancer

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