MCL1 expression

Blocking JAK-STAT signaling significantly improved the efficacy of radiotherapy for ESCC. These findings indicate that MCL1 is a critical cell cycle regulator that drives the stemness and radioresistance of ESCC and may thus be a potential target in a combined therapeutic strategy aimed at overcoming radioresistance.

P1, N=45, Recruiting, National Cancer Institute (NCI) | Initiation date: Jul 2025 --> Dec 2024

Our data showed a strong correlation between MCL-1 and distinct immune biomarkers and TME CI in CRC. Our findings suggest MCL-1 is a potential modulator of antitumor immunity, TME, and biomarker in CRC.

KRASG12C inhibitors sotorasib and adagrasib have been approved for the treatment of KRASG12C-mutant non-small cell lung cancer (NSCLC)...Through unbiased high-throughput screening of 1,395 kinase inhibitors, we identified adavosertib, a WEE1 inhibitor, as a promising combination partner of sotorasib...Importantly, WEE1 inhibition re-sensitized resistant cells to sotorasib treatment. The current findings demonstrate that combined inhibition of KRASG12C and WEE1 not only exhibits synergistic antitumor efficacy but also overcomes resistance to KRASG12C inhibitors, thus representing a novel therapeutic strategy for KRASG12C-mutant NSCLC.

However, the clinical development of the small molecule BCL-XL inhibitor ABT-263 has been challenged on account of its on-target and dose-limiting toxicity. Meanwhile, we observed that SIAIS361034 significantly synergized with PTX to inhibit the growth of SCLC xenografts in vivo, without causing exacerbating PTX-induced neutropenia. Taken together, SIAIS361034, shows great potentiality in killing tumors cells, both as a monotherapy and in combination with PTX.

In this respect, the role of MCL-1S in the regulation of apoptosis-unrelated events of the mitochondria physiology, including mitochondria fission and fusion also remains to be determined. In this review, the structure and function of MCL-1S isoform, and MCL-1S-targeting approaches are discussed.

Additionally, dinaciclib affects different cell growth regulators like EGFR and STAT3 on gene and protein level, thus decreasing tumor growth. In summary, our study indicates that dinaciclib acts as a promising anti-tumorigenic agent in 2D and 3D in vitro BTC models and thus encourages further investigation.

Oral TUS markedly extended survival in subcutaneously and orthotopically inoculated xenograft models of FLT3 mutant human AML, was well tolerated, and delivered enhanced activity when combined with venetoclax or 5-azacytidine...Cells selected for stable acquired resistance to TUS exhibited increased BAX and hypersensitivity to venetoclax (1900-fold), navitoclax and MCL1 inhibitors. MV-4-11 FLT3-ITD clones expressing NRASG12D revealed that high-level expression of NRASG12D generated modest resistance to TUS and greater resistance to venetoclax (VEN), yet the TUS/VEN combination exhibited synergy in NRASG12D AML model. Favorable preclinical safety and pharmacology properties, the efficacy of the TUS/VEN combination in a murine model, and the synthetic lethal vulnerability to VEN that accompanies TUS resistance provide the basis for exploration of the TUS/VEN combination in patients with relapsed or refractory AML.

Compared to the conventional culture, there was (i) a lower expression of VCAM1 in both materials, (ii) a higher expression of CCL4 in collagen scaffolds, and (iii) a lower expression of CXCR4 and MCL1 (transcript variant 2) in collagen scaffolds, while it was higher in a CMC-PEG gel. Hence, culture in the material can suppress the expression of a pro-apoptotic gene (MCL1 in collagen scaffolds) or replicate certain gene expression patterns attributed to CLL cells in lymphoid organs (low CXCR4, high CCL4 in collagen scaffolds) or blood (high CXCR4 in CMC-PEG).

We corroborated these findings in human MM datasets, and in ex vivo patient MM cells. These preclinical studies suggest that ASAH1 may be a potential therapeutic target for the treatment of relapsed/refractory MM (RRMM).

JLJG was found to effectively modulate the expression levels of these proteins, as well as the expression of downstream genes including BCL2, MCL1, P21, and JAK1, STAT3, thereby inhibiting the IL-6/JAK/STAT3 signaling pathway. Consequently, this study demonstrates that JLJG prevents the postoperative recurrence of CRA by inhibiting the IL-6/JAK/STAT3 signaling pathway and its negative feedback loops.

Concurrently, the phosphorylated protein expression levels of p-ERK1/2, p-MSK1, p-P90RSK, and p-MEK1/2 were diminished following RA treatment. These results suggest that RA has the activity of anti-MM, and the MAPK/ERK signaling pathway is involved in the growth inhibition effect of RA on MM cells via cycle arrest and mitochondrial-pathway-dependent apoptosis.