P1/2, N=180, Not yet recruiting, AstraZeneca

P1, N=41, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | Trial completion date: Nov 2026 --> Apr 2026 | Trial primary completion date: Jul 2026 --> Feb 2026

Scheduled exercise at ZT2 significantly increased the amplitude of Per2, Per3, and Rev-Erbα expression rhythms in tumor tissue...TNF-α acrophase was shifted in the ZT2 group, indicating a temporal immunomodulatory effect. Consistently performing exercise at the same time of day enhances tumor circadian clock genes rhythmicity, supporting chrono-exercise as a potential non-pharmacological adjuvant in cancer treatment.

This suggests a limited response amplitude within the RMP/NRF2-high context...This dynamic accounts for the relatively lower inhibition observed in the overexpression context. The combined RMP/NRF2/PD-L1 signature proposes a mechanistically informed biomarker framework and suggests the potential for rational therapeutic combinations that pair PD-1 blockade with modulation of the redox pathway in HCC.

P1/2, N=0, Withdrawn, AstraZeneca | N=30 --> 0 | Trial completion date: Mar 2029 --> Dec 2025 | Active, not recruiting --> Withdrawn | Trial primary completion date: Mar 2029 --> Dec 2025

Inflachromene, an inhibitor of the chromatin remodelers HMGB1/2, decoupled mitochondrial bioenergetics from senolytic susceptibility, yielding SASP-null/miR146a-negative senescent cancer cells that were completely resistant to ABT-263/navitoclax and A1331852 despite extensive mitochondrial reprogramming. Thus, the senolytic response is governed by a layered circuit in which mitochondrial bioenergetic heritage establishes the senolytic ceiling, TIS-acquired bioenergetic flexibility fine-tunes the amplitude of the senolytic response, and establishing a mitochondria-inflammatory SASP crosstalk is required for BH3-mediated senolysis. These results support using functional readouts that integrate mitochondrial metabolic flexibility and inflammatory SASP to predict and potentially enhance senolytic efficacy in TIS cancer cells.

P2/3, N=253, Recruiting, AstraZeneca AB

P1/2, N=700, Completed, Centre Leon Berard

BCL-2 overexpression reduced the number of Ca²+ puffs across all IP3R isoforms without affecting the amplitude or duration of individual puffs. Thus, BCL-2 acts as a universal inhibitor of all three IP3R isoforms, highlighting its critical role in fine-tuning intracellular Ca2+ dynamics to promote cell survival and its potential as a therapeutic target in cancer via its role in Ca2+ signalling.

Repeated doses on consecutive days do not improve the amplitude of the immune response following virus infusion. Furthermore, without improving therapeutic efficacy, repeated viral dosing leads to an unwanted influx of activated T-cells into background liver, alongside elevated liver enzymes associated with aberrant liver function. A single dose of reovirus is as effective as multiple doses when combined with anti-PD-L1 therapy in limiting tumour growth and extending survival in vivo, whilst simultaneously avoiding undesirable toxicities in background liver, in the context of HCC.

However, GRP78 expression did not exhibit a significant correlation with progressive sperm motility, average path velocity, curvilinear velocity, straight-line velocity, and amplitude of lateral head displacement. These results provide novel insights into the correlation between GRP78 and sperm motility, as well as its potential implications for male fertility.

This preliminary report suggests that intracordal bFGF injection may be effective for some cases even with severe vocal fold scar caused by radiotherapy, while the effects for burn-related scar remain unclear. Further investigation in a larger cohort is warranted to explore more information about the therapy.