ArticleBMC medicine2021
Functional apoptosis profiling identifies MCL-1 and BCL-xL as prognostic markers and therapeutic targets in advanced thymomas and thymic carcinomas.
Article in BMC medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Dual targeting of BCL-XL and MCL-1 exposes a rapid and exploitable apoptotic vulnerability in non-small cell lung cancer.Cell death and differentiation · 2026Article
- Innovative strategies to overcome cancer drug resistance: from nanodelivery systems to targeted therapeutics.Discover oncology · 2026Review
- Pathobiology of thymic epithelial tumours and the treatment strategy based on immuno-oncological characteristics: a narrative review.Mediastinum (Hong Kong, China) · 2026Review
- Proteasome inhibition as a potential therapeutic target in thymic cancer.Cell death & disease · 2025Article
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- In vitro analysis of the molecular mechanisms of ursolic acid against ovarian cancer.BMC complementary medicine and therapies · 2025Article
- Cell Culture Models for Translational Research on Thymomas and Thymic Carcinomas: Current Status and Future Perspectives.Cancers · 2024Review
- The Proteostasis of Thymic Stromal Cells in Health and Diseases.The protein journal · 2024Review
- Non-Mutational Key Features in the Biology of Thymomas.Cancers · 2024Review
- Review
- Genetic profile of thymic epithelial tumors in the Japanese population: an exploratory study examining potential therapeutic targets.Translational lung cancer research · 2023Article
- Article
- Unraveling molecular networks in thymic epithelial tumors: deciphering the unique signatures.Frontiers in immunology · 2023Review
- Noxa and Mcl-1 expression influence the sensitivity to BH3-mimetics that target Bcl-xL in patient-derived glioma stem cells.Scientific reports · 2022Article
- Targeted therapies for cancer.BMC medicine · 2022Article
- Oxidative Stress in Intervertebral Disc Degeneration: New Insights from Bioinformatic Strategies.Oxidative medicine and cellular longevity · 2022Article
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Authors and funding
12 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundMulti-omics studies have shown a high and lack of common driver mutations in most thymomas (TH) and thymic carcinomas (TC) that hamper the development of novel treatment approaches. However, deregulation of apoptosis has been proposed as a common hallmark of TH and TC. BH3 profiling can be utilized to study the readiness of living cancer cells to undergo apoptosis and their dependency on pro-survival BCL-2 family proteins.
methodsWe screened a cohort of 62 TH and TC patient samples for expression of BCL-2 family proteins and used the TC cell line 1889c and native TH for dynamic BH3 profiling and treatment with BH3 mimetics.
resultsImmunohistochemical overexpression of MCL-1 and BCL-xL was a strong prognostic marker of TH and TC, and BH3 profiling indicated a strong dependency on MCL-1 and BCL-xL in TH. Single inhibition of MCL-1 resulted in increased binding of BIM to BCL-xL as an escape mechanism that the combined inhibition of both factors could overcome. Indeed, the inhibition of MCL-1 and BCL-xL in combination induced apoptosis in a caspase-dependent manner in untreated and MCL-1-resistant 1889c cells.
conclusionTH and TC are exquisitely dependent on the pro-survival factors MCL-1 and BCL-xL, making them ideal candidates for co-inhibition by BH3 mimetics. Since TH show a heterogeneous dependency on BCL-2 family proteins, upfront BH3 profiling could select patients and tailor the optimal therapy with the least possible toxicity.
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