Proteomics for identifying mechanisms and biomarkers of drug resistance in cancer

Li, Xinhui; Cui, Li; Xiao, Zhi‐Qiang

doi:10.1016/j.jprot.2011.09.004

Cited by 26 publications

(22 citation statements)

References 53 publications

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“…A large proportion of the World population depends on the traditional medicine because of the shortage and high expenses of orthodox medicine (Dutta and Maharia, 2012;Li et al, 2011;Sultana et al, 2011). Natural products play a central role in the development of novel drug for the treatment and prevention of diseases (Khan et al, 2015;Sharma et al, 2015;Yu et al, 2013;Dhanamani et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Assessment of dual inhibitory activity of epifriedelanol isolated from Cayratia trifolia against ovarian cancer

Palanisamy

Sowmya

Velmurugan

et al. 2016

Bangladesh J Pharmacol

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Cayratia trifolia is used as diuretic, in tumors, neuralgia and splenopathy. However, compounds depicting anti-ovarian cancer activities from this plant source have not yet been identified and structurally characterized till date. In the present study, X-ray structure of epifriedelanol, a bioactive compound, isolated from the ethanolic extract of the C. trifolia and its binding affinities against a few proteins (HER2, EGFR and CXCR4) that are reported to get overexpressed under ovarian cancer had been thoroughly studied by using molecular docking means. Binding affinities of the compound vis-à-vis that of carboplatin, a FDA approved drug to the ovarian cancer, to interact with the protein targets are quite impressive. The drug-likeness properties of the epifriedelanol and scope to develop the compound as a potent anti-ovarian cancer drug are discussed in this paper.

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Section: Introductionmentioning

confidence: 99%

Assessment of dual inhibitory activity of epifriedelanol isolated from Cayratia trifolia against ovarian cancer

Palanisamy

Sowmya

Velmurugan

et al. 2016

Bangladesh J Pharmacol

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“…This is a leading cause of fatalities from common cancers including lung cancer. Several proteins can mediate cell death resistance (1–3) including fibroblast growth factor 2 (FGF-2) (4–6). Indeed, we have shown that FGF-2 signalling leads to the assembly of a multi-protein complex comprising BRaf, protein kinase Cϵ and ribosomal S6 kinase 2 (S6K2) but not S6K1.…”

Section: Introductionmentioning

confidence: 99%

hnRNPA1 couples nuclear export and translation of specific mRNAs downstream of FGF-2/S6K2 signalling

Roy

Durie

et al. 2014

Nucleic Acids Research

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The increased cap-independent translation of anti-apoptotic proteins is involved in the development of drug resistance in lung cancer but signalling events regulating this are poorly understood. Fibroblast growth factor 2 (FGF-2) signalling-induced S6 kinase 2 (S6K2) activation is necessary, but the downstream mediator(s) coupling this kinase to the translational response is unknown. Here, we show that S6K2 binds and phosphorylates hnRNPA1 on novel Ser4/6 sites, increasing its association with BCL-XL and XIAP mRNAs to promote their nuclear export. In the cytoplasm, phosphoS4/6-hnRNPA1 dissociates from these mRNAs de-repressing their IRES-mediated translation. This correlates with the phosphorylation-dependent association of hnRNPA1 with 14-3-3 leading to hnRNPA1 sumoylation on K183 and its re-import into the nucleus. A non-phosphorylatible, S4/6A mutant prevented these processes, hindering the pro-survival activity of FGF-2/S6K2 signalling. Interestingly, immunohistochemical staining of lung and breast cancer tissue samples demonstrated that increased S6K2 expression correlates with decreased cytoplasmic hnRNPA1 and increased BCL-XL expression. In short, phosphorylation on novel N-term sites of hnRNPA1 promotes translation of anti-apoptotic proteins and is indispensable for the pro-survival effects of FGF-2.

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“…Novel approaches to control drug resistance include functional genomics and proteomics [494,495]. RNA interference based screening provides a valuable opportunity for the examination of intrinsic and acquired resistance mechanisms.…”

Section: Tme Mediated Drug Resistancementioning

confidence: 99%

A New Approach to Cancer Therapy: The Tumor Microenvironment as Target

Schwendener¹,

Mete²

2013

Frontiers in Clinical Drug Research - Anti-Cancer Agents

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Solid tumors grow within a complex microenvironment composed of diverse cell types such as fibroblasts, endothelial cells, mast cells, macrophages and immune cells that are attracted by tumor cell derived factors and embedded in an extracellular matrix. Molecular and cellular interactions between epithelial cells and cells surrounding the tumor stroma promote growth, invasion and spread of tumors. To delay or impede tumor growth, the tumor microenvironment (TME) is increasingly being explored as a potential therapeutic target for which novel strategies are developed. lt;/pgt;lt;pgt; This article reviews how key interactions between tumor cells and surrounding mesenchymal and immune cells in the TME can promote tumor progression and it highlights cellular and molecular elements that might represent novel therapeutic targets. Special emphasis is given on therapies targeted towards tumor-associated macrophages. As main class of drugs the bisphosphonates are covered with their properties to repolarize a pro-tumorigenic, immunosuppressive environment to a tumor growth inhibiting and immunocompetent microenvironment. Properties and advantages of liposome-encapsulated bisphosphonates as macrophage depleting or modulating agents as well as the latest developments towards clinical applications of compounds targeting cellular and molecular components of the TME are described and reviewed. This article reviews how key interactions between tumor cells and surrounding mesenchymal and immune cells in the TME can promote tumor progression and it highlights cellular and molecular elements that might represent novel therapeutic targets. Special emphasis is given on therapies targeted towards tumor-associated macrophages. As main class of drugs the bisphosphonates are covered with their properties to repolarize a pro-tumorigenic, immunosuppressive environment to a tumor growth inhibiting and immunocompetent microenvironment. Properties and advantages of liposome-encapsulated bisphosphonates as macrophage depleting or modulating agents as well as the latest developments towards clinical applications of compounds targeting cellular and molecular components of the TME are described and reviewed.

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Proteomics for identifying mechanisms and biomarkers of drug resistance in cancer

Cited by 26 publications

References 53 publications

Assessment of dual inhibitory activity of epifriedelanol isolated from <i>Cayratia trifolia</i> against ovarian cancer

Assessment of dual inhibitory activity of epifriedelanol isolated from <i>Cayratia trifolia</i> against ovarian cancer

hnRNPA1 couples nuclear export and translation of specific mRNAs downstream of FGF-2/S6K2 signalling

A New Approach to Cancer Therapy: The Tumor Microenvironment as Target

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