scholarly journals Tumor Hybrid Cells: Nature and Biological Significance

2021 ◽  
Author(s):  
Maria S Tretyakova ◽  
Ayalur Raghu Subbalakshmi ◽  
Maxim E Menyailo ◽  
Mohit Kumar Jolly ◽  
Evgeny Denisov
Keyword(s):  
Drug Resistance ◽  
Tumor Cell ◽  
Cell Fusion ◽  
Cancer Metastasis ◽  
Experimental Studies ◽  
Biological Significance ◽  
Genetic Alterations ◽  
Clinicopathological Parameters ◽  
Cancer Drug ◽  
Hybrid Cells

Metastasis is the leading cause of cancer death and can be realized through the phenomenon of tumor cell fusion. The fusion of tumor cells with other tumor or normal cells leads to the appearance of tumor hybrid cells (THCs) exhibiting novel properties such as increased proliferation and migration, drug resistance, decreased apoptosis rate and avoiding immune surveillance. Experimental studies showed the association of THCs with a high frequency of cancer metastasis; however, the underlying mechanisms remain unclear. Many other questions also remain to be answered: the role of genetic alterations in tumor cell fusion, the molecular landscape of cells after fusion, the lifetime and fate of different THCs, and the specific markers of THCs, and their correlation with various cancers and clinicopathological parameters. In this review, we discuss the factors and potential mechanisms involved in the occurrence of THCs, the types of THCs, and their role in cancer drug resistance and metastasis, as well as potential therapeutic approaches for the prevention and targeting of tumor cell fusion. In conclusion, we emphasize the current knowledge gaps in the biology of THCs that should be addressed to develop highly effective therapeutics and strategies for metastasis suppression.

A Combined Bioinformatic and Nanoparticle-Based Study Reveal the Role of ABCG2 in the Resistance of Breast Cancer

2021 ◽  
Vol 16 ◽  
Author(s):  
Qin Huo ◽  
Jianhui Yuan ◽  
Ting Zhu ◽  
Zhenwei Li ◽  
Ni Xie
Keyword(s):  
Breast Cancer ◽  
Magnetic Nanoparticles ◽  
Genetic Alterations ◽  
Functional Enrichment ◽  
Clinicopathological Parameters ◽  
Cancer Drug ◽  
Cancer Resistance ◽  
Breast Cancer Patients ◽  
Chemotherapy Drugs ◽  
Anti Cancer

Background: ATP-Binding Cassette subfamily G member 2 (ABCG2) is a semi-transport protein that plays a key role in human diseases, including bladder cancer and lung cancer, and may be resistant to chemotherapy drugs. Objective: The present study aimed to determine the role and underlying mechanisms of breast cancer resistance protein (ABCG2) in breast cancer. To study the reversal effect of inhibiting ABCG2 expression on the drug resistance of breast cancer cells, and provide new ideas for gene targeted therapy of breast cancer. Methods: The structure and genomic alterations of ABCG2 were systematically investigated using GeneCards and cBioPortal to reveal the genetic alterations (including amplification and deep deletions) of ABCG2. We performed the correlation between ABCG2 expression and clinicopathological parameters using the data in bc-GenExMiner 4.4. Then, the protein-protein interaction and functional enrichment analysis of ABCG2 were performed based on the STRING, bc-GenExMiner 4.4, and Enrichr databases. Besides, we analyzed the pathway activity of genes that interact with ABCG2 using GSCALite and PharmGKB. Using magnetic nanoparticles polyMAG as the carrier of ABCG2-siRNA, polyMAG-ABCG2-siRNA was transfected into the Doxorubicin (DOX)-resistant breast cancer cell line MCF-7/ADR and directly into the tumors in nude mice. Patent US20150328485 points out that magnetic nanoparticles can be attached to an anti-cancer drug, such as an antibody-based anti-cancer drug. Results: We found statistically significant correlation between ABCG2 expression and clinicopathological parameters, such as Estrogen Receptor (ER), Progesterone Receptor (PR), and human epidermal growth factor receptor-2 (HER2), and nodal status in breast cancer patients. ABCG2 is closely related to SLC2A9, KIT, ABCG1, and MRPS7, which suggests that these proteins may be functional partners of breast cancer. The expression of ABCG2 is correlated with the activation or inhibition of multiple oncogenic pathways. Moreover, we found that ABCG2 is involved in the DOX signaling pathway. The small interfering RNA (siRNA) carried by magnetic nanoparticles can reduce the expression of ABCG2, thereby significantly improving the therapeutic effect of DOX on tumors. Conclusion: Our findings provide a more in-depth understanding of ABCG2 as a biomarker for predicting DOX-resistance and insights into the development of related therapeutic targets in breast cancer.

Medicinal and Biological Significance of Phenoxazine Derivatives

2020 ◽  
Vol 20 ◽  
Author(s):  
Jaya Dwivedi ◽  
Neetu Yaduvanshi ◽  
Shruti Shukla ◽  
Sonika Jain
Keyword(s):  
Drug Resistance ◽  
Biological Significance ◽  
Biological Application ◽  
Pharmacological Activities ◽  
Resistance Reversal ◽  
Anti Inflammatory ◽  
Pharmacological Application

: Since 1887, phenoxazine derivatives have attracted attention of chemist due to its versatile utility, industrially and pharmacologically. Literature is found abundant with various pharmacological activities of phenoxazine derivatives like antitumor, anticancer, antifungal, antibacterial, anti-inflammatory, anti-diabetic, anti-viral, anti-malarial, antidepressant, analgesic and many other drug resistance reversal activities. This review covers detailed over-view on pharmacological application of phenoxazine nucleus, its chemistry and reactivity and also illustrating the incorporation of different group at different positions enhancing its biological application, besides some synthetic procedures.

Fanconi Anemia DNA Repair Pathway as a New Mechanism to Exploit Cancer Drug Resistance

2020 ◽  
Vol 20 (9) ◽  
pp. 779-787
Author(s):  
Kajal Ghosal ◽  
Christian Agatemor ◽  
Richard I. Han ◽  
Amy T. Ku ◽  
Sabu Thomas ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Dna Repair ◽  
Fanconi Anemia ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Cancer Drugs ◽  
Repair Pathway ◽  
Cancer Drug Resistance ◽  
Anti Cancer ◽  
Cancerous Cells

Chemotherapy employs anti-cancer drugs to stop the growth of cancerous cells, but one common obstacle to the success is the development of chemoresistance, which leads to failure of the previously effective anti-cancer drugs. Resistance arises from different mechanistic pathways, and in this critical review, we focus on the Fanconi Anemia (FA) pathway in chemoresistance. This pathway has yet to be intensively researched by mainstream cancer researchers. This review aims to inspire a new thrust toward the contribution of the FA pathway to drug resistance in cancer. We believe an indepth understanding of this pathway will open new frontiers to effectively treat drug-resistant cancer.

Discovery of Novel 2-Amino-5-(Substituted)-1,3,4-Thiadiazole Derivatives: New Utilities for Colon Cancer Treatment

2018 ◽  
Vol 18 (5) ◽  
pp. 719-738 ◽  
Author(s):  
Vinit Raj ◽  
Amit Rai ◽  
Ashok K. Singh ◽  
Amit K. Keshari ◽  
Prakruti Trivedi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Metastasis ◽  
Molecular Targets ◽  
Cancer Cell Line ◽  
Chemotherapeutic Agents ◽  
Cancer Drug ◽  
Human Colon Cancer ◽  
Thiadiazole Derivatives ◽  
Ht 29

Background: Colon cancer is one of the most widespread disease, the mortality rate is high due to cancer metastasis and the development of drug resistance. In this regards, new chemotherapeutic agents with specific mechanisms of action and significant effect on patient’s survival are the new era for the colon cancer drug development. Objective: The main objective of present study was to design, synthesize of a novel series of 1,3,4-thiadiazole derivatives (VR1 to VR35) and screen them against HT-29 human colon cancer cell line. Method: Newly 1,3,4-thiadiazole scaffold were designed, synthesized and further, characterized by FTIR, NMR (1H and 13C), MS and elemental analyses. Before the synthesis, molecular dynamic simulation and ADME studies were performed to find out the most potent lead compounds. Later, SRB assay using HT-29 cells and ELISA assays were performed to explore activity and molecular targets of VR24 and VR27 and find out whether in silico data had a similar pattern in the molecular level. Results: The results of docking study revealed that both VR24 and VR27 had interaction energy >-5 kcal/mol with various assigned molecular targets and the ligand-protein complexes were found to be stable with IL-6. The computational analysis of molecules showed good ADMET profiling. Later, the in vitro anticancer study was conducted where VR24 and VR27 were found to be active against HT-29 cells (GI50<10 µM). Finally, ELISA assays revealed that both the compounds had higher inhibition properties to various biomarker of colon cancer like IL-6 and COX-2. Conclusion: Collectively, these result suggested that VR24 and VR27 inhibited the assigned molecular targets, imparting their ameliorative effects against colon cancer. Due to these encouraging results, we concluded that both VR24 and VR27 may be effective against colon cancer therapy in future.

Clinical applications of circulating tumor DNA in monitoring breast cancer drug resistance

2020 ◽  
Vol 16 (34) ◽  
pp. 2863-2878
Author(s):  
Yang Liu ◽  
Qian Du ◽  
Dan Sun ◽  
Ruiying Han ◽  
Mengmeng Teng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Resistance Mechanisms ◽  
Clinical Applications ◽  
Current Status ◽  
Cancer Drug ◽  
Genomic Alteration ◽  
Tumor Dna

Breast cancer is one of the leading causes of cancer-related deaths in women worldwide. Unfortunately, treatments often fail because of the development of drug resistance, the underlying mechanisms of which remain unclear. Circulating tumor DNA (ctDNA) is free DNA released into the blood by necrosis, apoptosis or direct secretion by tumor cells. In contrast to repeated, highly invasive tumor biopsies, ctDNA reflects all molecular alterations of tumors dynamically and captures both spatial and temporal tumor heterogeneity. Highly sensitive technologies, including personalized digital PCR and deep sequencing, make it possible to monitor response to therapies, predict drug resistance and tailor treatment regimens by identifying the genomic alteration profile of ctDNA, thereby achieving precision medicine. This review focuses on the current status of ctDNA biology, the technologies used to detect ctDNA and the potential clinical applications of identifying drug resistance mechanisms by detecting tumor-specific genomic alterations in breast cancer.

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