Estybon (rigosertib)

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.

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

We identified 100 total drug hits and found that STAG2 KO sensitized cells to treatment with PLK1 inhibitor rigosertib, whereas STAG2 KO protected cells from treatment with MEK inhibitor TAK-733 and PI3K inhibitor PI-103. Finally, synergy experiments revealed that berzosertib exhibits significant synergistic cytotoxicity in combination with cisplatin against MIBC cells. Altogether, our study presents evidence that berzosertib, PI-103, and the combination of berzosertib with cisplatin may be novel opportunities to investigate as precision medicine approaches for MIBC patients based on STAG2 tumor expression.

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.

Rigosertib, volasertib, and onvansertib showed equivalent efficacy to that of standard care agents (irinotecan and cisplatin) in vivo with significant growth inhibition superior to cisplatin in PDX models of platinum-sensitive and platinum-resistant SCLC. We established the efficacy of PLK1 inhibitors in vitro and in vivo using PDX models of platinum-sensitive and resistant relapsed SCLC. An ongoing phase II trial is currently testing the efficacy of onvansertib in patients with SCLC (NCT05450965).

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