This was accompanied by reduced expression of AKT1 and ABCB1 genes, reinforcing the anticancer efficacy of PD/SOF combination therapy. In conclusion, the findings suggest that PD/SOF could serve as a promising anticancer treatment strategy, warranting further investigation for potential clinical applications and mechanistic studies in vivo.

Linperlisib showed an acceptable safety profile and preliminary clinical benefit in patients with a range of advanced solid tumors. Further studies of linperlisib safety and efficacy are warranted.

Inhibiting PI3K/Akt with LY294002, Capivasertib (AZD5363), or using an inactive Akt mutant significantly increased p35 expression and subsequently enhanced AR stability and activation in PCa cells. Importantly, CDK5 knockdown further reduced PI3K/Akt-inhibition-induced AR and cell viability maintenance, suggesting a compensatory role for CDK5-AR in maintaining cell viability under Akt inhibition. In conclusion, PI3K/Akt inhibition could trigger p35-CDK5-dependent AR activation and cell viability, highlighting p35-CDK5 as a critical link connecting PI3K/Akt inhibition to AR activation and pivotal in PCa cell resistance to PI3K/Akt blockade.

This study elucidated the potential effects of Corynoxine in suppressing proliferation and metastasis in LUAD, along with investigating the underlying mechanisms. These data highlight the promise of Corynoxine as a novel therapeutic tool for the treatment of individuals diagnosed with LUAD.

FMN treatment significantly reduced the release of inflammatory cytokines and inhibited the effects of the PI3K/Akt signaling pathway on the key targets IL-4 and NOS3. Our results suggest FMN therapy as a novel therapeutic strategy for treating CRF.

Re-expression of GBE1 in shGBE1 cells alleviated apoptosis and reduced PX-478- induced apoptosis and pathway downregulation. In conclusion, our findings provide convincing evidence that PX-478 induces apoptosis by inhibiting the PI3K/AKT/mTOR pathway through downregulation of GBE1 in AML cells.

TRIM21 may represent a therapeutic target for tumors, and inhibiting TRIM21 could be a potential strategy for tumor treatment.

P2, N=51, Recruiting, Fudan University | Trial completion date: Sep 2025 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2026

P2, N=26, Not yet recruiting, ChongQing university cancer hospital; ChongQing university cancer hospital

P2, N=42, Recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

P2, N=30, Not yet recruiting, The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

P2, N=57, Recruiting, Cancer Hospital Chinese Academy of Medical Sciences; Cancer Hospital Chinese Academy of Medical Sciences

P1, N=24, Not yet recruiting, Kazia Therapeutics

P1, N=20, Terminated, Hoffmann-La Roche | Phase classification: P3 --> P1

Moreover, A549 and H460 cells treated with both combinations demonstrated augmented caspase-3 levels, implying substantial apoptotic activity. Altogether, these results accentuated the prospective implementation of sericin in combination with dactolisib and vitamin D at low doses to preclude lung cancer cell proliferation.

The PI3K inhibitor (LY294002) could reverse the effects of MCM4 on MM cells. MCM4 could substantially prompt the tumor growth of MM in mice through the PI3K/AKT pathway in vivo. In summary, MCM4 prompted the development and metastasis of MM by activating the PI3K/AKT pathway.

Compound 17p demonstrated comparable PI3Kα inhibitory activity (IC50: 31.8 ± 4.1 nM) to the positive control, BKM-120 (IC50: 44.6 ± 3.6 nM)...In a pharmacokinetic study, 17p was stable (T ½: 2.03 h) and showed high bioavailability (46.2%). Collectively, these results indicate that 17p could be a promising PI3K agent for cancer treatment.

P2, N=47, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting

P2, N=44, Not yet recruiting, Zhejiang Cancer Hospital

Moreover, inhibition of the Akt/mTOR signaling pathway with LY294002 (a PI3K inhibitor) enhanced the protective effect of Lut against Cd-induced cell death by suppressing Cd-induced activation of Akt, mTOR, and eukaryotic initiation factor 4E binding protein 1. The results showed that Lut prevented Cd-induced cell death partly by blocking the Akt/mTOR signaling pathway. Lut may be a potential agent for preventing Cd-induced nerve cell damage and neurodegenerative diseases.

To evaluate the efficacy of a novel histone deacetylase inhibitor, chidamide, in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (CR-CHOP) in the treatment of DEL. The most common grades 3-4 hematologic and nonhematologic toxicity were leukopenia (46.7%) and infection (21%), respectively. This long-term follow-up study indicates that CR-CHOP in untreated DLBCL with the DEL phenotype demonstrates high short-term efficacy and safety as well as promising survival outcomes.

Dalpiciclib plus fulvestrant is effective and comparatively safe in postmenopausal women with hormone receptor-positive and HER2-negative breast cancers. Dalpiciclib, buparlisib, fulvestrant, and ribociclib cause neutropenia, severe depression, adverse gastroenterological effects, and adverse hepatological effects, respectively.

P=N/A, N=25, Not yet recruiting, Peking University People's Hospital

The prototype epoxytigliane, EBC-46 (tigilanol tiglate), is a potent anti-cancer agent in clinical development for local treatment of a range of human and animal tumors...PKC-βI/-βII isoform inhibition by enzastaurin (1 μM), significantly inhibited HaCaT proliferation and wound repopulation responses induced by both epoxytiglianes, especially at 1.51-151 nM. PKC-α inhibitor, Ro 31-8220 mesylate (10 nM), exerted lesser inhibitory effects on HaCaT responses...Phospho-PKC (p-PKC) studies confirmed that epoxytiglianes transiently activated classical PKC isoforms (p-PKCα, p-PKC-βI/-βII, p-PKCγ) in a dose- and time-dependent manner. By identifying how epoxytiglianes stimulate classical PKCs to facilitate keratinocyte healing responses and re-epithelialization, these findings support further epoxytigliane development as topical therapeutics for clinical situations involving impaired re-epithelialization, such as non-healing wounds in skin.

We studied this problem using cell lines representing diffuse large B-cell lymphoma (SUDHL-4 and OCI-Ly7), a genetically-encoded live-cell reporter of AKT activity, and 3 small-molecule inhibitors targeting different levels of the pathway: idelalisib (PI3Kδ), GSK2334470 (PDPK1), and ipatasertib (AKT)...Combining all 3 inhibitors produced sustained inhibition of AKT activity, was broadly synergistic at reducing viable cell number, enabled substantially lower doses of each inhibitor to be used, and was enhanced further by the mTOR inhibitor rapamycin...In a syngeneic mouse cell line model of lymphoma (A20), the triple combination showed antitumor activity and no evidence of toxicity. Our findings provide proof of concept suggesting further study of the safety and efficacy of low-dose multilevel PI3K/AKT pathway inhibition, for lymphoma and perhaps other cancers.

Using FRET and Biolayer Interferometry assays, we show that a class of ATP-site directed inhibitors represented by GSK2126458 block the growth factor activated PI3KαWT membrane interaction, an activity dependent on the ligand forming specific ATP-site interactions...We find that an ATP substrate analogue can increase the wild type PI3Kα membrane interaction, uncovering a substrate based regulatory event that can be mimicked by different inhibitor chemotypes. Our findings, together with the discovery of small molecule allosteric activators of PI3Kα illustrate that PI3Kα membrane interactions can be modulated by factors related to ligand binding both within the ATP site and at allosteric sites.

To evaluate the effect of the PI3K/AKT pathway on TNFRSF11B, LY294002, a PI3K/AKT pathway inhibitor, was utilized...In BC, TNFRSF11B exhibits elevated expression levels and has a substantial tumor-promoting role in BC via the PI3K/AKT pathway. Importantly, TNFRSF11B may represent a valuable prognostic tumor marker for BC treatment.

It also inhibited the PI3K/AKT pathway to regulate the expression of Bax and Bcl-2, thereby initiating the Caspase cascade to activate mitochondrial mediated apoptosis. Furthermore, 11a suppressed tumor growth in breast cancer syngeneic models with no apparent toxicity.

Chidamide combined with (+)-JQ-1 can inhibit the proliferation of MLL-r AML cells, inhibit the initiation of protective self-repair of these leukemia cells by inhibiting the DNA damage response pathway, and ultimately increase the apoptosis of these cells, but non- MLL-r AML cells have no similar results.

BXD has the effect of inhibiting tumor growth rate and delaying the development of GC. Its mechanism of action may be related to the regulation of PI3K-Akt signaling pathway.

Here, we conducted a study of the metabolic and signaling implications associated with autophagy induced by glutamine (Gln) and serum starvation and PI3K/mTOR inhibitor and autophagy inducer NVP-BEZ235 (BEZ) in the head and neck squamous cell carcinoma (HNSCC) cell line FaDu...We also found that alterations in the release of inflammatory cytokines constitute a principal response to autophagy induction. Importantly, the specific mechanism driving autophagy induction significantly influenced the composition of the EVs-associated cytokine secretome.

This research provides insight into the potential of ZSTK474 and other PI3K inhibitors for treating nephroblastoma.

The results of molecular dynamics indicated that Silibinin could stably bind to PI3Kδ. Silibinin was a structurally novel 3,5,7-trihydroxychroman-4-one PI3Kδ inhibitor, providing valuable information for the subsequent discovery of PI3Kδ inhibitors.

The therapeutic effect of various nanohybrids were validated in the mice with spontaneous tumor in the colorectal area and tumor-bearing mice, which lead to the increase of ferroptosis, the activation of STING signaling pathway, and the repolarization of macrophages. Collectively, the cGAMP and IPI-549 co-loaded nanohybrids effectively reshaped the tumor immune microenvironment, and exhibited prominent treatment effect of anti-colorectal cancer in vitro, patient-derived organoids, and in vivo.

In addition, Gas6 knockdown downregulated the levels of P-PI3K and P-AKT. Taken together, the findings confirm that Gas6 knockdown can inhibit esophageal cancer progression and can exert anti-tumor effects on esophageal cancer through the PI3K/AKT pathway.

Our study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.

P1, N=63, Active, not recruiting, Adlai Nortye Biopharma Co., Ltd. | Trial primary completion date: Sep 2024 --> Dec 2024

P2, N=76, Recruiting, Ruijin Hospital | Trial primary completion date: Jun 2024 --> Jun 2025

Targeting this pathway has been approved as a therapeutic option for breast cancer and lymphoma (e.g. alpelisib, idelalisib), and there are several clinical trials underway in additional types of cancer...We report the case of a 53-year-old female with metastatic breast cancer who developed acute grade 3 hyperglycemia from a novel PI3K inhibitor, inavolisib...All patients treated with PI3K inhibitors should receive pre-treatment screening for hyperglycemia, lifestyle advice, and a glucometer to measure fasting BGL and 2-h post-dinner BGL levels twice per week for at least the first 30 days of treatment. Insulin or insulin secretagogues (e.g. sulfonylurea) may inhibit the anti-tumor activity of PI3K inhibitors, and thus treatment of PI3K inhibitor-associated hyperglycemia should prefer alternative approaches such as a low carbohydrate diet, metformin, SGLT2i, or dose reduction of the PI3K inhibitor.

P=N/A, N=400, Not yet recruiting, Ruijin Hospital

Notably, our study identified eight drugs-Bortezomib, Midostaurin, CHIR.99021, JNK.Inhibitor.VIII, Lenalidomide, Sunitinib, GDC0941, and GW.441756-as exhibiting sensitivity toward OS. The outcomes of this investigation present an opportunity to predict the survival outcomes among individuals diagnosed with OS. Furthermore, these findings hold promise for progressing research endeavors focused on prognostic evaluation and therapeutic interventions pertaining to this particular ailment.

P1/2, N=138, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed