tosedostat (CHR-2797)

Drug prediction and molecular docking identified chlorendic acid, idarubicin, PHA-848,125, and tosedostat as potential activators of the OAS family due to their strong binding affinity. Conversely, GW842166, NSC 23,766, and metolazone showed high binding affinity for OASL and may inhibit its expression. In summary, The OAS gene family, associated with poor prognosis in gastric cancer, promotes tumour progression and represents a promising therapeutic target.

The H103 randomized 679 patients between standard first-line intensive chemotherapy with or without selinexor, tosedostat, or lenalidomide, in 3 consecutive randomizations. Selected NCR-patients were comparable with H103-controls for most patient characteristics present in both databases. However, a significantly lower OS was observed for NCR-patients. The lack of recorded performance status and absence of comorbidity and toxicity scores in NCR-patients might explain these differences.

We confirm that NPEPPS is associated with cisplatin-resistance in an ex vivo MIBC tumoroid model. These findings have potential for rapid translation into the clinic and invite trials investigating tosedostat to overcome chemoresistance.

Treatments included: Low dose Ara-C (LDAC) alone, sapacitabine alone and LDAC in combination with vosaroxin, tosedostat or ganetespib (MRC/NCRI); Azacytidine (AZA) alone, tipifarnib alone, and AZA in combination with mylotarg, midostaurin, and nivolumab (SWOG). Our ability to predict early death in older patients treated with lower intensity AML therapies is limited with routinely available clinical variables. Inclusion of cytogenetic risk, FLT3-ITD, and NPM1 mutation status minimally improved the prognostic accuracy as did some of the QLQ-C30 subscales. Our data highlight the difficulties in predicting outcomes with non-intensive AML therapy with routinely available baseline clinical information.