Anti-tumor effects of rigosertib in high-risk neuroblastoma

Radke, Katarzyna; Hansson, Karin; Sjölund, Jonas; Wolska, Magdalena; Karlsson, Jenny; Esfandyari, Javanshir; Pietras, Kristian; Aaltonen, Kristina; Gisselsson, David; Bexell, Daniel

doi:10.1016/j.tranon.2021.101149

Cited by 10 publications

(12 citation statements)

References 33 publications

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“…The 100 nm Rig concentration is consistent with Rig concentrations used in other studies; in fact, in all these works, Rig exhibited the same efficacy in reducing the viability of the cell lines evaluated, with effective concentrations starting approximately at 50–100 nM [ 6 , 14 , 15 , 16 , 17 , 18 ].…”

Section: Resultssupporting

confidence: 86%

“…Moreover, Rig is capable of inducing senescence or cell death by apoptosis in several tumor cell lines, both in vitro and in vivo [ 4 , 6 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ], increasing the production of ROS and altering the expression of numerous proteins involved in apoptosis (p53, BAX, MDM2) and in the formation of metastases (E-cadherins, matrix metalloproteinases 2 and 9) [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…In the last few years, Rig has been evaluated in several clinical trials for the treatment of myelodysplastic syndromes, alone or in combination with other drugs [ 20 , 21 , 22 , 23 ]. Furthermore, various articles in literature have demonstrated the efficacy of Rig in vitro also in different types of solid tumors, such as colorectal cancer (SW48 and CaCo2 cells), neuroblastoma (LU-NB1, LU-NB2, LU-NB3 cells), retinoblastoma (Y79 and patient derived cells), hepatocellular carcinoma (Hep3B cells), head and neck cancer (UM-SCC cells), and colangiocarcinoma (EGI-1 cells) [ 6 , 14 , 15 , 16 , 17 , 18 ]. The aim of our work is to investigate if Rig could represent an effective anticancer agent also in other type of tumor lines.…”

Section: Introductionmentioning

confidence: 99%

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Another Brick to Confirm the Efficacy of Rigosertib as Anticancer Agent

Malacrida

Deschamps-Wright

Rigolio

et al. 2023

IJMS

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Rigosertib is a small molecule in preclinical development that, due to its characteristics as a dual PLK1 and PI3K inhibitor, is particularly effective in counteracting the advance of different types of tumors. In this work, we evaluated the efficacy of Rigosertib and the expression of p53 in five different human tumor cell lines in vitro, A549 (lung adenocarcinoma), MCF-7 and MDA-MB231 (breast cancer cells), RPMI 8226 (multiple myeloma), and U87-MG (glioblastoma). We demonstrated that in all cell lines, the effect was dose- and time-dependent, but A549 cells were the most sensible to the treatment while higher concentrations were required for the most resistant cell line U87-MG. Moreover, the highest and lowest p53 levels have been observed, respectively, in A459 and U87-MG cells. The alterations in the cell cycle and in cell-cycle-related proteins were observed in A549 at lower concentrations than U87-MG. In conclusion, with this article we have demonstrated that Rigosertib has different efficacy depending on the cell line considered and that it could be a potential antineoplastic agent against lung cancer in humans.

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Section: Resultssupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Another Brick to Confirm the Efficacy of Rigosertib as Anticancer Agent

Malacrida

Deschamps-Wright

Rigolio

et al. 2023

IJMS

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“…Neuroblastoma (NB) and Wilms tumor (WT) are two of the most common solid pediatric tumors, notorious for their rapid growth. We estimated growth rates from previously published data on untreated patientderived xenografts (PDX) derived from NB and WT 5,[19][20][21][22] . For comparison with adult tumors (i.e., slow growers) 23 , we also evaluated the uninhibited growth of several lung and breast cancer cell lines (unpublished data).…”

Section: Resultsmentioning

confidence: 99%

Evolutionary unpredictability in cancer model system

Chattopadhyay

Karlsson

Mañas

et al. 2022

Preprint

Self Cite

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With the advent of precision cancer medicine, a lot of focus is now on characterization of genomic variations in each individual tumor instead of describing all cancers of the same site under one umbrella. This has resulted in a fine-tuned prognostication of many tumors by predicting the probable course of the disease based on each cancers molecular signature. Yet, the threat of a relapse and a consequent treatment resistant runaway disease loom in many cases. Tracing cellular lineages to elucidate clonal evolution has revealed how tumors evolve in different evolutionary trajectories and resistant clones often appear due to excessive branching early in the disease and remain dormant only to clonally fixate afterwards. Multiregional sequencing has further revealed how the genomic signature carries spatial stochasticity. Disorganized genomic rearrangements was theorized as genome chaos. Shifting our vision away from the deterministic nature of Somatic Mutation Theory it is important to reconcile that cancer is not a purely stochastic phenomenon, rather result of runaway dysregulations in a complex and dynamic system. Generalized logistic model is a commonly used construct in simulating spatially constricted growth of cancer cell populations. Simulations show that evolutionary trajectories of cancers are highly dependent on how cell populations grow and how they interact with the stromal boundary and just so it happens, logistic map produces chaotic oscillation under certain growth parameters. We here probe the question whether the logistic function as a mechanism for tumor growth can explain emergent diversity in clonal geographies in tumorigenesis and if it invokes chaos.

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“…More recently, the efficacy and mechanism of rigosertib have been tested in rhabdomyosarcoma (RMS) and neuroblastoma (NBs) cell lines. Here, the authors showed that the main cytotoxic effect is due to an efficient cell arrest in mitosis, mainly by interfering with mitotic spindle assembly, which leads to cell death [46,47]. In fact, the authors have shown a similar behavior of rigosertib with respect to other Vinca alkaloids, although it is better tolerated.…”

Section: Rigosertib As a Tubulin Polymerization Destabilizermentioning

confidence: 94%

Lights and Shadows on the Cancer Multi-Target Inhibitor Rigosertib (ON-01910.Na)

Monfort-Vengut

Cárcer

2023

Pharmaceutics

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Rigosertib (ON-01910.Na) is a small-molecule member of the novel synthetic benzyl-styryl-sulfonate family. It is currently in phase III clinical trials for several myelodysplastic syndromes and leukemias and is therefore close to clinical translation. The clinical progress of rigosertib has been hampered by a lack of understanding of its mechanism of action, as it is currently considered a multi-target inhibitor. Rigosertib was first described as an inhibitor of the mitotic master regulator Polo-like kinase 1 (Plk1). However, in recent years, some studies have shown that rigosertib may also interact with the PI3K/Akt pathway, act as a Ras–Raf binding mimetic (altering the Ras signaling pathway), as a microtubule destabilizing agent, or as an activator of a stress-induced phospho-regulatory circuit that ultimately hyperphosphorylates and inactivates Ras signaling effectors. Understanding the mechanism of action of rigosertib has potential clinical implications worth exploring, as it may help to tailor cancer therapies and improve patient outcomes.

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Anti-tumor effects of rigosertib in high-risk neuroblastoma

Cited by 10 publications

References 33 publications

Another Brick to Confirm the Efficacy of Rigosertib as Anticancer Agent

Another Brick to Confirm the Efficacy of Rigosertib as Anticancer Agent

Evolutionary unpredictability in cancer model system

Lights and Shadows on the Cancer Multi-Target Inhibitor Rigosertib (ON-01910.Na)

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