Combination of microtubule targeting agents with other antineoplastics for cancer treatment

Liang, Tingting; Lu, Lu; Song, Xueting; Jing, Qi; Wang, Jianhong

doi:10.1016/j.bbcan.2022.188777

Cited by 15 publications

(14 citation statements)

References 135 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Exploration of the use of microtubules has shown potential positive effects in prognosis prediction in cancer patients. As a major part of the eukaryotic cytoskeleton, microtubules serve as molecular highways and contribute to the exchange of cellular cargo ( Roehlecke and Schmidt, 2020 ; Liang et al, 2022 ). Furthermore, they consist of spindle apparatus that play a crucial role in the correct attachment and segregation of chromosomes during cell division ( Kavallaris, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of microtubule-associated biomarkers in diffuse large B-cell lymphoma and prognosis prediction

Liu

Tian

et al. 2023

Front. Genet.

View full text Add to dashboard Cite

Background: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease with a complicated prognosis. Even though various prognostic evaluations have been applied currently, they usually only use the clinical factors that overlook the molecular underlying DLBCL progression. Therefore, more accurate prognostic assessment needs further exploration. In the present study, we constructed a novel prognostic model based on microtubule associated genes (MAGs).Methods: A total of 33 normal controls and 1360 DLBCL samples containing gene-expression from the Gene Expression Omnibus (GEO) database were included. Subsequently, the univariate Cox, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were used to select the best prognosis related genes into the MAGs model. To validate the model, Kaplan-Meier curve, and nomogram were analyzed.Results: A risk score model based on fourteen candidate MAGs (CCDC78, CD300LG, CTAG2, DYNLL2, MAPKAPK2, MREG, NME8, PGK2, RALBP1, SIGLEC1, SLC1A1, SLC39A12, TMEM63A, and WRAP73) was established. The K-M curve presented that the high-risk patients had a significantly inferior overall survival (OS) time compared to low-risk patients in training and validation datasets. Furthermore, knocking-out TMEM63A, a key gene belonging to the MAGs model, inhibited cell proliferation noticeably.Conclusion: The novel MAGs prognostic model has a well predictive capability, which may as a supplement for the current assessments. Furthermore, candidate TMEM63A gene has therapeutic target potentially in DLBCL.

show abstract

Section: Introductionmentioning

confidence: 99%

Identification of microtubule-associated biomarkers in diffuse large B-cell lymphoma and prognosis prediction

Liu

Tian

et al. 2023

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…For many years, microtubule-targeting agents (MTAs) have represented effective drugs for cancer treatment. Different classes of MTAs are used to treat solid tumors, principally taxanes (paclitaxel, docetaxel, cabazitaxel), vinca-alkaloids (vinorelbine, vincristine), and a few others (epothilone, eribulin) [ 1 , 2 ]. They represent potent cytotoxic agents which are useful for blocking tumor cell growth, and display additional key properties such as decreasing angiogenesis and cell migration, reducing metastasis, and activating innate immunity to promote a proinflammatory response [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, the use of these compounds is limited by significant toxicities (notably peripheral neuropathies) and the development of multidrug resistance. These limitations can be reduced upon combination with targeted molecules, such as kinase inhibitors or immune checkpoint inhibitors, but nevertheless the search for novel MTAs is needed to improve cancer treatments [ 2 ]. Novel anti-tubulin drugs continue to be designed and evaluated experimentally [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Docking of Cryptoconcatones to α-Tubulin and Related Pironetin Analogues

Vergoten

Bailly

2023

Plants

View full text Add to dashboard Cite

Cryptoconcatones A-L represent a series of 12 dihydropyrone derivatives isolated from the evergreen tree Cryptocarya concinna Hance, which is well distributed in southeast Asia. The lead compound in the series, cryptoconcatone L, has revealed antiproliferative activity against cultured cancer cells but its mechanism of action remains unknown. Based on a structural analogy with the anticancer natural product pironetin, which is well known for binding covalently to α-tubulin and for functioning as a microtubule polymerization inhibitor, we investigated the interaction of cryptoconcatones with tubulin dimers using molecular docking. The α-tubulin binding capacity of each compound was quantified (through calculation of the empirical energy of interaction ΔE) and structure–binding relationships were delineated. Two compounds were found to interact with α-tubulin much more potently than pironetin: cryptoconcatones F and L. In both cases, the facile formation of a covalent bond with Cys316 was evidenced, as observed with the parent compound pironetin. A few other pironetin analogues were investigated, including spicigerolide, which is an analogue of another known α-tubulin binder. Altogether, this study points to the identification of a series of 5,6-dihydro-α-pyrones as α-tubulin-binding agents. The study contributes to a better understanding of the mechanism of action of cryptoconcatones and should help the design of analogues targeting the pironetin site of α-tubulin.

show abstract

“…As a key component of the eukaryotic cytoskeleton, microtubules play an important role in pivotal cellular functions such as mitosis, cell signal transduction, and intracellular trafficking; therefore, it is becoming a significant target for cancer therapy . Microtubule targeting agents (MTAs), such as paclitaxel, are effectively used for BC clinical treatment to induce BC cell cycle arrest and apoptosis by interfering with spindle microtubule dynamics, while their clinical applications are limited by drug toxicity and the development of resistance. , Therefore, it is necessary to explore novel MTAs such as dual-target inhibitors to improve efficacy and reduce toxicities. Moreover, selenium-containing compounds have been identified as potential therapeutic agents for various diseases, including cancer, stroke, and diabetes. , It has been demonstrated that Na 2 SeO 3 could inhibit tubulin polymerization by forming disulfide bonds between the sulfhydryl groups of tubulin, which leads to the conformational change of protein, but it exhibits high toxicity in vivo . , Selenocyanate, as a metabolite of selenite in mammalian cells, possesses lower cytotoxicity and more potent antitumor activity.…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel Dual-Target Estrogen Receptor α Degraders with Tubulin Inhibitory Activity for the Treatment of Endocrine-Resistant Breast Cancer

Deng

Ning

et al. 2023

J. Med. Chem.

View full text Add to dashboard Cite

Endocrine resistance remains a significant problem in the clinical treatment of estrogen receptor α-positive (ERα + ) breast cancer (BC). In this study, we developed a series of novel dual-functional ERα degraders based on a bridged bicyclic scaffold with selenocyano (SeCN) side chains. These compounds displayed potent ERα degradation and tubulin depolymerization activity. Among them, compounds 35s and 35t exhibited the most promising antiproliferative and ERα degradation activity in multiple ERα + BC cell lines bearing either wild-type or mutant ERα. Meanwhile, compounds 35s and 35t disrupted the microtubule network by restraining tubulin polymerization, evidenced by 35t inducing cell cycle arrest in the G2/M phase. In MCF-7 and LCC2 xenograft models, compounds 35s and 35t remarkably suppressed tumor growth without noticeable poisonousness. Finally, this study provided guidance for developing new dual-target antitumor drug candidates for the ERα + BC therapy, especially for the resistant variant.

show abstract

Combination of microtubule targeting agents with other antineoplastics for cancer treatment

Cited by 15 publications

References 135 publications

Identification of microtubule-associated biomarkers in diffuse large B-cell lymphoma and prognosis prediction

Identification of microtubule-associated biomarkers in diffuse large B-cell lymphoma and prognosis prediction

Molecular Docking of Cryptoconcatones to α-Tubulin and Related Pironetin Analogues

Identification of Novel Dual-Target Estrogen Receptor α Degraders with Tubulin Inhibitory Activity for the Treatment of Endocrine-Resistant Breast Cancer

Contact Info

Product

Resources

About