Emerging evidence suggests rigosertib's potential in paediatric cancers like neuroblastoma and its synergy with therapies such as MEK inhibitors and hypomethylating agents. Future research should focus on optimizing combination strategies, identifying predictive biomarkers, and improving drug delivery to enhance its clinical efficacy and applicability across diverse cancer types.

In summary, our investigation identifies a molecular vulnerability in c-Myc-driven TNBC, where Ras inhibition reinforces c-Myc-targeted therapy and potentiates immune checkpoint blockade, presenting a promising strategy to improve immunotherapy efficacy in TNBC.

P1, N=3, Completed, Thomas Jefferson University | Active, not recruiting --> Completed

Moreover, rigosertib induced caspase-1 activation and gasdermin cleavage leading to Nod-like receptor pyrin domain-containing 3 (NLRP3)-dependent inflammatory responses in human lung cancer organoids. Our results suggest that rigosertib may effectively inhibit RAS-MAPK signaling and reprogram the tumor immune environment, presenting the potential for a potent therapeutic strategy in cancer treatment.

P1, N=6, Active, not recruiting, Thomas Jefferson University | Recruiting --> Active, not recruiting

Ras pathway inhibitors Trametinib and Rigosertib suppressed the lethality but not the reduced size phenotypes. In contrast, the lack of effects on the reduced size phenotypes would be consistent with small stature resulting from Raf- and PI3K-independent processes. We propose that this model can be useful for future mechanistic analysis and pharmacological screening and evaluation.

In a genome-wide CRISPR-Cas9 resistance drug screen, we identified and validated the master osmostress regulator WNK1 kinase as a modulator of the response to the mitotic inhibitor rigosertib...This promotes resistance to microtubule depolymerizing compounds, and increased sensitivity to microtubule stabilizing drugs. In summary, our data proposes WNK1 osmoregulation activity as an important modulator for microtubule-associated chemotherapy response.

P2, N=29, Suspended, Vanderbilt-Ingram Cancer Center | Recruiting --> Suspended

Moreover, 13b displayed superior antitumor efficacy (TGI, 61.3 %) than the single administration of Ola (TGI, 38.5 %), 11b (TGI, 51.8 %) or even their combined administration (TGI, 56.7 %), but did not show significant systematic toxicity. These findings suggest that 13b may serve as a potential candidate for BRCA wild-type TNBC.

Our project suggested that the prognostic model with apoptotic features can effectively predict prognosis in CCA patients, proffering prognostic biomarkers and potential therapeutic targets for CCA patients.

P1/2, N=25, Completed, Icahn School of Medicine at Mount Sinai | Recruiting --> Completed

Among them, two representative compounds, XSJ-7 and XSJ-10, not only showed stronger antiproliferative activity against many types of cancer cells including solid tumor cells but also presented more potent inhibition on different subtypes of HDAC than suberoylanilide hydroxamic acid (SAHA). Significantly, XSJ-10 presented moderate pharmacokinetic behaviors and showed stronger antitumor activity than oxaliplatin, SAHA, and rigosertib in the HT-29 xenograft mouse models without significant systemic toxicity. Research on the anticancer mechanism of XSJ-10 revealed that it can effectively induce the apoptosis of cancer cells and suppress the tumor by strongly inhibiting the RAS-RAF-MEK-ERK signaling pathway and the acetylation level of HDAC3.