Resistance acquisition to MDM2 inhibitors

2014 ◽  
Vol 42 (4) ◽  
pp. 752-757 ◽  
Author(s):  
Jindrich Cinatl ◽  
Daniel Speidel ◽  
Ian Hardcastle ◽  
Martin Michaelis
Keyword(s):  
Clinical Trials ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Small Molecule ◽  
P53 Mutations ◽  
Experimental Systems ◽  
Anti Cancer ◽  
Double Minute ◽  
Murine Double Minute ◽  
Experimental Strategies

Various experimental strategies aim to (re)activate p53 signalling in cancer cells. The most advanced clinically are small-molecule inhibitors of the autoregulatory interaction between p53 and MDM2 (murine double minute 2). Different MDM2 inhibitors are currently under investigation in clinical trials. As for other targeted anti-cancer therapy approaches, relatively rapid resistance acquisition may limit the clinical efficacy of MDM2 inhibitors. In particular, MDM2 inhibitors were shown to induce p53 mutations in experimental systems. In the present article, we summarize what is known about MDM2 inhibitors as anti-cancer drugs with a focus on the acquisition of resistance to these compounds.

scholarly journals MDM2 Amplified Sarcomas: A Literature Review

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 496
Author(s):  
Raf Sciot
Keyword(s):  
Suppressor Gene ◽  
Negative Regulator ◽  
Low Grade ◽  
P53 Mutations ◽  
Lipomatous Tumor ◽  
Double Minute ◽  
Genetic Features ◽  
Murine Double Minute ◽  
Well Differentiated ◽  
Mdm2 Amplification

Murine Double Minute Clone 2, located at 12q15, is an oncogene that codes for an oncoprotein of which the association with p53 was discovered 30 years ago. The most important function of MDM2 is to control p53 activity; it is in fact the best documented negative regulator of p53. Mutations of the tumor suppressor gene p53 represent the most frequent genetic change in human cancers. By overexpressing MDM2, cancer cells have another means to block p53. The sarcomas in which MDM2 amplification is a hallmark are well-differentiated liposarcoma/atypical lipomatous tumor, dedifferentiated liposarcoma, intimal sarcoma, and low-grade osteosarcoma. The purpose of this review is to summarize the typical clinical, histopathological, immunohistochemical, and genetic features of these tumors.

scholarly journals Epigenetic Research in Stem Cell Bioengineering—Anti-Cancer Therapy, Regenerative and Reconstructive Medicine in Human Clinical Trials

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1016 ◽  
Author(s):  
Claudia Dompe ◽  
Krzysztof Janowicz ◽  
Greg Hutchings ◽  
Lisa Moncrieff ◽  
Maurycy Jankowski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cancer Therapy ◽  
Regulation Of Gene Expression ◽  
Epigenetic Modifications ◽  
Transcriptional Level ◽  
Cancer Therapies ◽  
Stem Cell Engineering ◽  
Anti Cancer

The epigenome denotes all the information related to gene expression that is not contained in the DNA sequence but rather results from chemical changes to histones and DNA. Epigenetic modifications act in a cooperative way towards the regulation of gene expression, working at the transcriptional or post-transcriptional level, and play a key role in the determination of phenotypic variations in cells containing the same genotype. Epigenetic modifications are important considerations in relation to anti-cancer therapy and regenerative/reconstructive medicine. Moreover, a range of clinical trials have been performed, exploiting the potential of epigenetics in stem cell engineering towards application in disease treatments and diagnostics. Epigenetic studies will most likely be the basis of future cancer therapies, as epigenetic modifications play major roles in tumour formation, malignancy and metastasis. In fact, a large number of currently designed or tested clinical approaches, based on compounds regulating epigenetic pathways in various types of tumours, employ these mechanisms in stem cell bioengineering.

scholarly journals Anticancer activity of pyrithione zinc in oral cancer cells identified in small molecule screens and xenograft model: Implications for oral cancer therapy

2015 ◽  
Vol 9 (8) ◽  
pp. 1720-1735 ◽  
Author(s):  
Gunjan Srivastava ◽  
Ajay Matta ◽  
Guodong Fu ◽  
Raj Thani Somasundaram ◽  
Alessandro Datti ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Oral Cancer ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Small Molecule ◽  
Xenograft Model ◽  
Oral Cancer Cells

ErbB4 increases the proliferation potential of human lung cancer cells and its blockage can be used as a target for anti-cancer therapy

2006 ◽  
Vol 119 (2) ◽  
pp. 269-274 ◽  
Author(s):  
Alex Starr ◽  
Joel Greif ◽  
Akiva Vexler ◽  
Maia Ashkenazy-Voghera ◽  
Valery Gladesh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Anti Cancer ◽  
Human Lung Cancer Cells ◽  
Proliferation Potential

scholarly journals A Literature Review on High-Performance Photocatalysts for Sustainable Cancer Therapy

Crystals ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1241
Author(s):  
Hanxi Yi ◽  
Zeneng Cheng
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
High Performance ◽  
Active Oxygen Species ◽  
Stable Production ◽  
Anti Cancer ◽  
Reaction Performance ◽  
Materials Used ◽  
Photodynamic Reaction ◽  
Photocatalytic Materials

Since cancer is a serious threat to public health worldwide, the development of novel methods and materials for treating cancer rapidly and thoroughly is of great significance. This review summarizes the mechanism and application of photocatalytic materials used to kill cancer cells. The photosensitivity and toxicological properties of several common photcatalysts used in anti-cancer treatment are discussed in detail. The ideal photocatalyst must possess the following characteristics: a highly stable production of active oxygen species and high selectivity to cancer cells without causing any damage to healthy tissues. This work concluded the existing photocatalytic materials used to treat cancer, as well as the current challenges in the application of cancer therapy. We aim to provide a basis for the development of new photocatalytic anti-cancer materials with high stability and selectivity while maintaining high photodynamic reaction performance.

scholarly journals Sensitization of glycoengineered interferon-β1a-resistant cancer cells by cFLIP inhibition for enhanced anti-cancer therapy

Oncotarget ◽  
2017 ◽  
Vol 8 (8) ◽  
pp. 13957-13970 ◽  
Author(s):  
Tae-Eun Kim ◽  
Sungyoul Hong ◽  
Kyoung Song ◽  
Sang-Ho Park ◽  
Young Kee Shin
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Anti Cancer

scholarly journals Magnetic Alginate / Chitosan Nanoparticles for Targeted Delivery of Curcumin into Human Breast Cancer Cells

2018 ◽  
Author(s):  
Wenxing Song ◽  
Xing Su ◽  
David Gregory ◽  
Wei Li ◽  
Zhiqiang Cai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Breast Cancer Cells ◽  
Chitosan Nanoparticles ◽  
Cancer Drug ◽  
Uptake Efficiency ◽  
Anti Cancer ◽  
Hdf Cells

Curcumin is a promising anti-cancer drug but its applications in cancer therapy are limited due to its poor solubility, short half-life and low bioavailability. In this study, curcumin loaded magnetic alginate / chitosan nanoparticles were fabricated to improve the bioavailability, uptake efficiency and cytotoxicity of curcumin to MDA-MB-231 breast cancer cells. Alginate and chitosan were deposited on Fe3O4 magnetic nanoparticles based on their electrostatic properties. The sizes of the nanoparticles (120-200 nm) were within the optimum range for drug delivery. Sustained curcumin release was obtained use the nanoparticles with the ability to control the curcumin release rate by altering the number of chitosan and alginate layers. Confocal fluorescence microscopy results showed that targeted delivery of curcumin with the aid of magnetic field were achieved. The FACS assay indicated that MDA-MB-231 cells treated with curcumin loaded nanoparticles had a 3-6 folds uptake efficiency to those treated with free curcumin. MTT assay indicated that the curcumin loaded nanoparticles exhibited significantly higher cytotoxicity toward MDA-MB-231 cells than toward HDF cells. The sustained release profiles, enhanced uptake efficiency and cytotoxicity to cancer cells as well as the targeting potential make MACPs a promising candidate for cancer therapy.

scholarly journals Dual Targeting of Cancer Cells with DARPin-Based Toxins for Overcoming Tumor Escape

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3014 ◽  
Author(s):  
Elena Shramova ◽  
Galina Proshkina ◽  
Victoria Shipunova ◽  
Anastasia Ryabova ◽  
Roman Kamyshinsky ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Tumor Escape ◽  
Simultaneous Treatment ◽  
Repeat Proteins ◽  
Dual Targeting ◽  
Anti Cancer ◽  
Comparable Effect ◽  
Ankyrin Repeat Proteins ◽  
Pseudomonas Aeruginosa Exotoxin

We report here a combined anti-cancer therapy directed toward HER2 and EpCAM, common tumor-associated antigens of breast cancer cells. The combined therapeutic effect is achieved owing to two highly toxic proteins—a low immunogenic variant of Pseudomonas aeruginosa exotoxin A and ribonuclease Barnase from Bacillus amyloliquefaciens. The delivery of toxins to cancer cells was carried out by targeting designed ankyrin repeat proteins (DARPins). We have shown that both target agents efficiently accumulate in the tumor. Simultaneous treatment of breast carcinoma-bearing mice with anti-EpCAM fusion toxin based on LoPE and HER2-specific liposomes loaded with Barnase leads to concurrent elimination of primary tumor and metastases. Monotherapy with anti-HER2- or anti-EpCAM-toxins did not produce a comparable effect on metastases. The proposed approach can be considered as a promising strategy for significant improvement of cancer therapy.

scholarly journals MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 29 ◽  
Author(s):  
Hyun Ah Seo ◽  
Sokviseth Moeng ◽  
Seokmin Sim ◽  
Hyo Jeong Kuh ◽  
Soo Young Choi ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Therapeutic Resistance ◽  
Cancer Therapies ◽  
Anti Cancer ◽  
Different Types ◽  
Therapeutic Responses

The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.

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