P2, N=17, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2025 --> Nov 2026

P1, N=22, Active, not recruiting, National Cancer Institute (NCI) | N=85 --> 22 | Trial completion date: Jun 2026 --> Nov 2026 | Trial primary completion date: Jun 2026 --> Nov 2025

Mechanistically, CXCL3 activated the PI3K/AKT/mTOR pathway by upregulating PI3K, p-PI3K, AKT, p-AKT, mTOR, and p-mTOR, while the mTOR inhibitor Torin 1 reversed these effects...In vivo, CXCL3 overexpression significantly promoted tumor growth in nude mice. These findings suggest CXCL3 facilitates liver cancer progression through tumor microenvironment modulation and PI3K/AKT/mTOR pathway activation.

Pharmaco-transcriptomic analysis revealed that IL3RA-high AML exhibited selective sensitivity to venetoclax and sapanisertib, suggesting potential synergistic opportunities. In conclusion, IL3RA overexpression defines a clinically and biologically distinct subgroup of AML, with unique therapeutic vulnerabilities. Continued research efforts are warranted to integrate CD123-directed therapies into the upfront AML treatment paradigm.

P1, N=99, Active, not recruiting, AstraZeneca | Trial completion date: Sep 2028 --> Feb 2026

Drug sensitivity analysis revealed differences in the IC50 values of OSI-027, PLX-4720, UMI-77, and Sapitinib between the high-risk and low-risk groups. Enrichment analysis revealed that these prognostic ARGs were primarily enriched in pathways and biological processes related to tumorigenesis. The risk model of ARGs can effectively predict READ prognosis and provide potential therapeutic targets.

Notably, both chloroquine treatment and ULK1-S757E transfection abolished the OSI-027/WZ4003 synergy. Moreover, elevated ARK5 expression was observed in HCC specimens and was independently associated with an unfavorable recurrence-free survival (RFS). Our findings propose a novel strategy for augmenting sensitivity to OSI-027 in HCC, further underscoring the significance of ARK5 and autophagy as cancer therapeutic targets.

Across multiple in vitro and in vivo CRC models, navitoclax enhanced PI3K/MTOR inhibition (copanlisib, sapanisertib, and dactolisib) and induced apoptosis. Furthermore, we identify BCL-xL as the major BCL-2 family target important for the response to this combination in this setting. This provides a strong rationale for MTORC1/2 and BCL-2 family inhibition as a potential treatment strategy for PIK3CA mutant CRCs.

In conclusion, the safety profile of onatasertib in combination with toripalimab was manageable and showed encouraging clinical activity in advanced solid tumors, particularly among cervical cancer patients, irrespective of PD-L1 expression. The recommended phase 2 dose for the combination was determined to be onatasertib 15 mg QD and toripalimab 240 mg Q3W.

Preclinical studies of Polyphyllin I and MTI31 illustrate the reversal of epithelial-mesenchymal transition and restoration of sensitivity to EGFR-targeted agents. In contrast to previous reviews, we offer a comparative analysis of monotherapy versus combination regimens, highlight remaining knowledge gaps, and propose an integrated framework for co-targeting EGFR, STAT3, and immune checkpoints. We aim to elucidate EGFR-STAT3 signaling crosstalk in NSCLC and distinguish preclinical findings from clinical data to enhance the translational relevance of combination therapies.

P1, N=85, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

P1, N=159, Active, not recruiting, M.D. Anderson Cancer Center | Phase classification: P1/2 --> P1