MCL1 as putative target in pancreatoblastoma

Reissig, Timm M.; Uhrig, Sebastian; Jost, Philipp J.; Luchini, Claudio; Vicentini, Caterina; Liffers, Sven-Thorsten; Allgäuer, Michael; Adsay, Volkan; Scarpa, Aldo; Lawlor, Rita T.; Fröhling, Stefan; Klöppel, Günter; Schildhaus, Hans–Ulrich; Siveke, Jens T.

doi:10.1007/s00428-022-03349-w

Cited by 5 publications

(3 citation statements)

References 37 publications

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“… Barbie et al (2014 ) have suggested that IKBKG was aberrantly expressed in breast carcinomas associated with NF-κB pathway activation. Myeloid cell leukemia-1 ( MCL1 ), a typical anti-apoptotic protein belonging to the oncogenic BCL-2 family, was originally identified in myeloid cells ( Reissig et al, 2022 ). MCL1 has been found to be overexpressed in many solid tumors, and many studies highlighted the potential importance of MCL1 as a therapeutic target ( Pereira-Castro et al, 2022 ; Quentmeier et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

A novel risk model based on anoikis: Predicting prognosis and immune infiltration in cutaneous melanoma

et al. 2023

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Cutaneous melanoma (CM) is a highly aggressive malignancy with a dimal prognosis and limited treatment options. Anoikis is believed to involve in the regeneration, migration, and metastasis of tumor. The exact role of anoikis-related genes (ARGs) in the development and progression of cutaneous melanoma, however, remains elusive. Four ARGs (SNAI2, TFDP1, IKBKG, and MCL1) with significant differential expression were selected through Cox regression and LASSO analyses. Data for internal and external cohorts validated the accuracy and clinical utility of the prognostic risk model based on ARGs. The Kaplan–Meier curve indicated a much better overall survival rate of low-risk patients. Notably, we also found that the action of ARGs in the CM was mediated by immune-related signaling pathways. Consensus clustering and TIME landscape analysis also indicated that the low-risk score patients have excellent immune status. Moreover, the results of immunotherapy response and drug sensitivity also confirmed the potential implications of informing individualized immune therapeutic strategies for CM. Collectively, the predictive risk model constructed based on ARGs provides an excellent and accurate prediction tool for CM patients. This present research provides a rationale for the joint application of targeted therapy and immunotherapy in CM treatment. The approach could have great therapeutic value and make a contribution to personalized medicine therapy.

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Section: Discussionmentioning

confidence: 99%

A novel risk model based on anoikis: Predicting prognosis and immune infiltration in cutaneous melanoma

et al. 2023

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“…Additionally, high-level amplification of Myeloid Cell Leukemia Sequence 1 ( MCL1) has been identified in a small percentage of pancreatoblastoma patients. The patients with MCL1 -amplified pancreatoblastoma could potentially benefit from targeted MCL1 inhibition[ 73 ].…”

Section: Molecular Pathologymentioning

confidence: 99%

Blastomas of the digestive system in adults: A review

Liu,

El Jabbour,

Somma

et al. 2024

World J Gastrointest Surg

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Blastomas, characterized by a mixture of mesenchymal, epithelial, and undifferentiated blastematous components, are rare malignant neoplasms originating from precursor blast cells. This review focuses on digestive system blastomas in adult patients, including gastroblastoma, hepatoblastoma, and pancreatoblastoma. Gastroblastoma is a biphasic, epitheliomesenchymal tumor, with only sixteen cases reported to date. In addition to the characteristic histology, metastasis-associated lung adenocarcinoma transcript 1 - glioma-associated oncogene homolog 1 gene fusion is typical, although recently novel ewing sarcoma breakpoint region 1 - c-terminal binding protein 1 and patched 1 - glioma-associated oncogene homolog 2 fusions have been described. Hepatoblastoma is exceptionally rare in adults and can show a variety of histologic patterns which may cause diagnostic difficulty. Pancreatoblastoma, primarily a pediatric tumor, displays acinar differentiation and squamoid nests with other lines of differentiation also present, especially neuroendocrine. Diagnostic approaches for these blastomas include a combination of imaging modalities, histopathological examination, and molecular profiling. The treatment generally involves surgical resection, which may be supplemented by chemotherapy or radiotherapy in some cases. Prognoses vary with gastroblastoma generally showing favorable outcomes post-surgery whereas hepatoblastoma and pancreatoblastoma often have poorer outcomes, particularly in the setting of metastases. This review highlights the complexity of diagnosing and managing these rare adult blastomas as well as the need for ongoing research to better understand their pathogenesis and improve treatment strategies.

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“…Also, the amplification of MCL1 can be observed in some patients with pancreatoblastoma (PB). This points to MCL1 as a possible target in PB; the inhibition of MCL1 in patients with MCL1-amplified cancer could be beneficial [6]. MCL1 is often upregulated in acute myeloblastic leukemia (AML) cells, which are often resistant to treatment with BCL2 inhibitors; however, the administration of an MCL1 inhibitor together with a BCL2 inhibitor leads to apoptosis in AML cells or animal models of AML [7].…”

Section: Introductionmentioning

confidence: 99%

Mcl-1 Protein and Viral Infections: A Narrative Review

Wyżewski,

Stępkowska,

Kobylińska

et al. 2024

IJMS

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MCL-1 is the prosurvival member of the Bcl-2 family. It prevents the induction of mitochondria-dependent apoptosis. The molecular mechanisms dictating the host cell viability gain importance in the context of viral infections. The premature apoptosis of infected cells could interrupt the pathogen replication cycle. On the other hand, cell death following the effective assembly of progeny particles may facilitate virus dissemination. Thus, various viruses can interfere with the apoptosis regulation network to their advantage. Research has shown that viral infections affect the intracellular amount of MCL-1 to modify the apoptotic potential of infected cells, fitting it to the “schedule” of the replication cycle. A growing body of evidence suggests that the virus-dependent deregulation of the MCL-1 level may contribute to several virus-driven diseases. In this work, we have described the role of MCL-1 in infections caused by various viruses. We have also presented a list of promising antiviral agents targeting the MCL-1 protein. The discussed results indicate targeted interventions addressing anti-apoptotic MCL1 as a new therapeutic strategy for cancers as well as other diseases. The investigation of the cellular and molecular mechanisms involved in viral infections engaging MCL1 may contribute to a better understanding of the regulation of cell death and survival balance.

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MCL1 as putative target in pancreatoblastoma

Cited by 5 publications

References 37 publications

A novel risk model based on anoikis: Predicting prognosis and immune infiltration in cutaneous melanoma

A novel risk model based on anoikis: Predicting prognosis and immune infiltration in cutaneous melanoma

Blastomas of the digestive system in adults: A review

Mcl-1 Protein and Viral Infections: A Narrative Review

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