Synthetic Lethal Targeting of Mitotic Checkpoints in HPV-Negative Head and Neck Cancer

Deneka, Alexander Y.; Einarson, Margret B.; Bennett, John M.; Nikonova, Anna S.; Elmekawy, Mohamed; Zhou, Yan; Lee, Jong Woo; Burtness, Barbara; Golemis, Erica A.

doi:10.3390/cancers12020306

Cited by 19 publications

(14 citation statements)

References 53 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on this strategy, in addition to suppressing the cell cycle, tumors can also be treated by the combination of chemotherapy and cell cycle regulation that drive the cell cycle. The principle is usually to cancel the circulating checkpoints of tumor cells [80]. For example, as shown in Fig.…”

Section: Combination Strategies Of Chemotherapeutic Drugs and Cell Cymentioning

confidence: 99%

Co-delivery of chemotherapeutic drugs and cell cycle regulatory agents using nanocarriers for cancer therapy

Sun

Jing

et al. 2021

Sci. China Mater.

View full text Add to dashboard Cite

Combination chemotherapy is widely exploited to overcome multidrug resistance (MDR) and enhance the therapeutic effect of anti-tumor agents clinically. The traditional combination regimens applied in clinical practice still suffer from various obstacles, such as inevitable side effects. Fortunately, the application of nanotechnology and the proposal of co-delivery systems make the combination therapy more effective. The occurrence, development, and metastasis of tumors are closely related to the cell cycle. The sensitivity of tumor cells to chemotherapeutic drugs can be improved with the cooperation of cell cycle regulators. In this review, the influence of the cell cycle on tumorigenesis and development is introduced briefly. The current strategies of combining chemotherapeutic drugs and cell cycle regulators through codelivery systems are discussed in detail. We also sketch the possibility of treating tumors mildly via artificially controlling the cell cycle and outline the challenges and perspectives about the improvement of co-delivery systems for cancer therapy.

show abstract

Section: Combination Strategies Of Chemotherapeutic Drugs and Cell Cymentioning

confidence: 99%

Co-delivery of chemotherapeutic drugs and cell cycle regulatory agents using nanocarriers for cancer therapy

Sun

Jing

et al. 2021

Sci. China Mater.

View full text Add to dashboard Cite

show abstract

“… 3 Moreover, HNSCC, with its alarmingly high incidence, affects >800,000 people annually worldwide. 4 The currently adopted standard clinical protocol for HNSCC is surgical intervention in combination with chemotherapy and radiation to eliminate any residual cancer cells. 5 However, the use of combination therapy is a promising aspect of oncology due to the underlying complexity of the immune system and various therapies for tumor evasion.…”

Section: Introductionmentioning

confidence: 99%

LINC00461 facilitates HNSCC development and reduces chemosensitivity by impairing miR-195-mediated inhibition of HOXA10

Guan

Chen

et al. 2021

Molecular Therapy - Oncolytics

View full text Add to dashboard Cite

Homeobox A10 (HOXA10) has been regarded to serve as an oncogene in head and neck squamous cell carcinoma (HNSCC). This study was intended to explore the interaction among the long intergenic noncoding RNA 00461 (LINC00461), microRNA (miR)-195, and HOXA10, and to investigate its role in epithelial-mesenchymal transition (EMT) and chemoresistance in HNSCC. The effects of LINC00461, miR-195, and HOXA10 on the EMT and chemoresistance of HNSCC cells were analyzed by comprehensive analysis of gain- and loss-of-function techniques. The intimate relationships among LINC00461, miR-195, and HOXA10 were investigated by several procedures such as RNA-binding protein immunoprecipitation, RNA pull-down, and dual-luciferase reporter assays. A xenotransplantation tumor model in nude mice was established for the assessment of the tumorigenic ability of the cells in vivo . Our findings indicated that LINC00461 was highly expressed in HNSCC and its overexpression induced EMT and precipitated the chemoresistance of HNSCC cells to cisplatin. The LINC00461 could bind to miR-195 while miR-195 targeted HOXA10 independently. Moreover, LINC00461 impaired miR-195-mediated inhibition of HOXA10 to induce EMT and increase the chemoresistance in HNSCC. Tumor weight and volume were reduced by lentivirus-mediated elevation of miR-195 by inhibition of HOXA10, which could be annulled by LINC00461 overexpression. LINC00461 downregulates the expression of miR-195 to subsequently upregulate the expression of HOXA10, thereby promoting EMT and enhancing chemoresistance in HNSCC.

show abstract

“…However, other mechanisms, such as DDR aberrations, nucleotide starvation, replicative stress, and, as more recently found, loss of the ATRX chromatin remodeler gene [ 36 ] and low phosphatase and tensin homolog (PTEN) expression [ 37 ], contribute to sensitize cancer cells to WEE1 inhibition, which, thus, proved monotherapy activity even in TP53 -wild-type cancer cells [ 29 , 30 , 38 ]. Moreover, WEE1 inhibition showed efficacy also in combination with inhibitors of other DDR factors, such as PARP [ 39 , 40 , 41 , 42 ], CHK1 [ 29 , 43 , 44 , 45 , 46 , 47 ], and ataxia telangiectasia and Rad3 related (ATR) kinase [ 48 , 49 , 50 ], and also when combined with different anticancer targeted agents [ 29 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ] and immunotherapeutic approaches [ 29 , 62 , 63 , 64 ].…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of the dl922-947 Oncolytic Virus in Malignant Mesothelioma Cell Lines

Iannuzzi

Indovina

Forte

et al. 2020

IJMS

View full text Add to dashboard Cite

Malignant mesothelioma (MM) is a very aggressive asbestos-related cancer, for which no therapy proves to be effective. We have recently shown that the oncolytic adenovirus dl922-947 had antitumor effects in MM cell lines and murine xenografts. Previous studies demonstrated that dl922-947-induced host cell cycle checkpoint deregulation and consequent DNA lesions associated with the virus efficacy. However, the cellular DNA damage response (DDR) can counteract this virus action. Therefore, we assessed whether AZD1775, an inhibitor of the G2/M DNA damage checkpoint kinase WEE1, could enhance MM cell sensitivity to dl922-947. Through cell viability assays, we found that AZD1775 synergized with dl922-947 selectively in MM cell lines and increased dl922-947-induced cell death, which showed hallmarks of apoptosis (annexinV-positivity, caspase-dependency, BCL-XL decrease, chromatin condensation). Predictably, dl922-947 and/or AZD1775 activated the DDR, as indicated by increased levels of three main DDR players: phosphorylated histone H2AX (γ-H2AX), phospho-replication protein A (RPA)32, phospho-checkpoint kinase 1 (CHK1). Dl922-947 also increased inactive Tyr-15-phosphorylated cyclin-dependent kinase 1 (CDK1), a key WEE1 substrate, which is indicative of G2/M checkpoint activation. This increase in phospho-CDK1 was effectively suppressed by AZD1775, thus suggesting that this compound could, indeed, abrogate the dl922-947-induced DNA damage checkpoint in MM cells. Overall, our data suggest that the dl922-947-AZD1775 combination could be a feasible strategy against MM.

show abstract

Synthetic Lethal Targeting of Mitotic Checkpoints in HPV-Negative Head and Neck Cancer

Cited by 19 publications

References 53 publications

Co-delivery of chemotherapeutic drugs and cell cycle regulatory agents using nanocarriers for cancer therapy

Co-delivery of chemotherapeutic drugs and cell cycle regulatory agents using nanocarriers for cancer therapy

LINC00461 facilitates HNSCC development and reduces chemosensitivity by impairing miR-195-mediated inhibition of HOXA10

Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of the dl922-947 Oncolytic Virus in Malignant Mesothelioma Cell Lines

Contact Info

Product

Resources

About