ArticleHealth science reports2025
Targeting MCL-1 to Overcome Therapeutic Resistance and Improve Cancer Mortality.
Article in Health science reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Natural products targeting the molecular pathology of salivary gland mucoepidermoid carcinoma: A systematic review of In vitro studies.Molecular biology reports · 2026Pooled it
- Dynamic ecosystems of tumor drug resistance mechanisms: from molecular heterogeneity to systemic interventions.Apoptosis : an international journal on programmed cell death · 2026Review
- Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies.Molecules (Basel, Switzerland) · 2026Review
- Adult Low-Grade Glioma WithCase reports in pathology · 2026Article
- SRSF1/Mcl-1 Axis Drives Apoptosis Evasion and Shapes the Immune Microenvironment to Promote Gastric Cancer Progression.Human mutation · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Myeloid cell leukemia-1 protein (MCL-1) is a major anti-apoptotic member of the Bcl-2 family and is typically overexpressed in a broad range of malignancies, including non-small-cell lung cancer, multiple myeloma, acute myeloid leukemia, and various solid tumors. By sequestering pro-apoptotic effectors, MCL-1 maintains mitochondrial stability and supports the tumor cell survival during stress, driving disease progression, therapeutic resistance, and ultimately, poor patient outcomes. In the last 10 years, the development of selective small-molecule inhibitors of MCL-1 has opened doors to enable the targeting of this mechanism of apoptosis avoidance. Discussion: This perspective summarizes the current knowledge regarding the dual roles of MCL-1 in apoptosis and mitochondrial homeostasis regulation. The structural foundations for the design of MCL-1 inhibitors are revisited, the pharmacological profiles of the leading drugs (S63845, AZD5991, AMG 176) in advanced clinical development are summarized, and emerging strategies, such as combination therapies with inhibitors of anti-apoptotic proteins such as BCL-2, PROTAC strategies designed to degrade MCL-1, and reversible-binding chemotypes to maximize MCL-1 inhibition and minimize toxicity, are reviewed. The non-apoptotic roles of MCL-1 in immune modulation and metabolism adaptation are also reviewed, along with the development of analytical methods to refine the patient selection process (e.g., BH3 profiling and transcriptomic signatures). The overexpression of MCL-1 is associated with worse patient survival in ACC, CESC, ESCA, HNSC, LGG, and UVM cancers. Conclusion: MCL-1 is an exciting anti-cancer target, and its inhibition may sensitize treatment-resistant tumors to cell death and enhance patient survival. The key to clinical success will be to carefully develop more intensive dosing regimens, rationally combine agents, and develop trial designs that prioritize the evaluation of new agents that maximize antitumor activity without the risk of off-target toxicities. Continued translational research and adaptive clinical trials are critical to fully realize the therapeutic potential of MCL-1 inhibition across various cancer contexts.
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