bims-midomi 2026-10-04 papers

Curr Treat Options Oncol. 2026 Sep 30. pii: 48. [Epub ahead of print]27(1):

Systemic Options for Recurrent Abdominal Low-grade Well-differentiated Liposarcoma.

Anna Boulouta, Antonia Digklia, Anastasia Stergioula, Anastasios Kyriazoglou.

OPINION STATEMENT: Well-differentiated liposarcoma (WDLPS) is a low-grade malignancy characterized by an indolent clinical course and a strong tendency for local recurrence. Unlike other sarcoma subtypes, pure WDLPS has a very low metastatic potential. However, in the course of the disease, dedifferentiation may occur and is associated with a substantially higher risk of metastases and mortality. Surgery remains the cornerstone of treatment for both primary and recurrent abdominal WDLPS, when a complete resection is possible. The role of systemic therapy in WDLPS is less clearly defined. Conventional cytotoxic chemotherapy generally has limited activity in pure WDLPS, and most clinical trials have included both WDLPS with dedifferentiated liposarcoma (DDLPS) or other liposarcoma subtypes, making the data for pure WDLPS difficult to interpret. Therefore, in clinical practice, we consider systemic treatment for patients with unresectable, symptomatic disease and in cases of repeated recurrences in which further local treatment is not possible. For selected patients with indolent and asymptomatic disease, active surveillance remains an appropriate strategy. The recent development of treatments directed against molecular alterations in WDLPS, namely CDK4 and MDM2 amplifications, have opened up a new era in the systemic treatment of this disease. Among these, anti-CDK4 agent palbociclib has shown the most mature clinical evidence to date, including recent results of overall survival data. MDM2 inhibition and combinations targeting both CDK4 and MDM2 represent promising areas which are currently under investigation. Due to the rarity of WDLPS and the lack of evidence from prospective studies, enrollment in clinical trials should be prioritized whenever possible.

Keywords: CDK4 inhibitor; MDM2 inhibitor; Recurrent disease; Retroperitoneal sarcoma; Systemic therapy; Well-differentiated liposarcoma

DOI: https://doi.org/10.1007/s11864-026-01414-z

Mol Biol Rep. 2026 Oct 01. pii: 1668. [Epub ahead of print]53(1):

Transient peak of p53 induction persists at low radiation doses in MCF-7 cells.

Irina Danilova, Jana Klementová, Šárka Jarošová, Pavel Kundrát, Martina Zíková, Marie Davídková.

BACKGROUND: The p53 protein is a central tumour suppressor regulating numerous genes involved in cell cycle control, DNA repair, and apoptosis. Mutations in p53 occur in over half of all cancers, disrupting these regulatory pathways and enhancing tumour progression. Many cell lines, including MCF-7 breast cancer cells, exhibit oscillatory p53 and MDM2 activity, a phenomenon linked to radiosensitivity and the cellular response to ionizing radiation.
METHODS AND RESULTS: We investigated the dose-dependent dynamics of p53 activation in MCF-7 cells exposed to γ-radiation in the dose range of 0.1 to 8 Gy. Using western blot analysis and real-time quantitative PCR, we examined dynamics of the expression of p53 and its downstream targets, including CDKN1A, GADD45A, and MDM2 genes. Our findings reveal that while oscillations in p53 and its downstream targets are prominent at high radiation doses, transient peak expression persists even at doses as low as 0.1 Gy, though with delayed onset and diminished amplitude.
CONCLUSIONS: The results extend the knowledge on p53 dynamics down to 0.1 Gy. They challenge the previous models that predicted the absence of oscillations at low radiation doses.

Keywords: Breast cancer cells MCF-7; Ionizing radiation; MDM2 oscillation; Transient peak expression; Tumour suppressor; p53 protein

DOI: https://doi.org/10.1007/s11033-026-12787-7

Front Oncol. 2026 ;16 1867524

Synergistic antitumor effect of HMGB2 targeting combined with MDM2 inhibitor in diffuse intrinsic pontine glioma therapy.

Bochao Zhang, Yuxuan Deng, Luyang Xie, Yiying Mai, Hang Zhou, Liwei Zhang.

Diffuse intrinsic pontine glioma (DIPG) is a brain malignancy in children with a dismal prognosis. The high mobility group box 2 (HMGB2) is a member of the HMGB family of chromatin-associated proteins, and is identified as a potential oncogene in various cancers. However, the effects of HMGB2 in DIPG remains unclear. In this study, we observed aberrant expression of HMGB2 in multiple cancer types, with its expression level being negatively correlated with clinical outcomes across pan-cancers. High expression of HMGB2 was determined in DIPG cells, but not in primary brainstem neural progenitor cells (PPCs). Knockdown of HMGB2 significantly inhibited the DIPG cell proliferation and induced cell apoptosis. Intriguingly, bulk RNA sequencing revealed that inhibition of HMGB2 upregulated p53 protein expression and enhanced the activity of p53-p21 axis. Combining HMGB2 inhibitor with a p53-MDM2 inhibitor RG7388 resulted in a synergistic suppression of DIPG cell growth and promoted cell apoptosis by activating the tumor suppressor p53 and p21 expressions in vitro. The animal studies demonstrated that the combination treatment significantly inhibited tumor growth and prolonged the survival of mice bearing orthotopic DIPG tumors. These findings demonstrate that HMGB2 acts as an oncogene in DIPG tumorigenesis, and targeting HMGB2 combined with MDM2 inhibitor provides a novel preclinical basis for the development of DIPG therapeutic strategies.

Keywords: DIPG; HMGB2; MDM2 inhibitor; combined therapy; inflachromene; tumor suppressor p53

DOI: https://doi.org/10.3389/fonc.2026.1867524

bioRxiv. 2026 Sep 24. pii: 2026.09.23.753860. [Epub ahead of print]

Topotecan Synergizes with SP141 in the Management of Uveal Melanoma.

Anju Thomas, Utkarsh R Addi, Audrianna Wu, Kaleigh Kozak, Ross F Collery, Amit Joshi, Aparna Ramasubramanian, Shyam S Chaurasia.

Purpose: Uveal melanoma (UM) is a rare but aggressive intraocular malignancy originating in the uvea (choroid, iris, and ciliary body). Despite primary treatment, 50% of UM patients develop metastases to the liver, lungs, bones, and skin. Topotecan, a topoisomerase I inhibitor, and SP141, an MDM2 inhibitor, have been studied in cancers, including retinoblastoma. This study explores a combined approach with these drugs in the 92-1 UM cell line.
Methods: Primary choroidal melanoma-derived 92-1 cells were treated with topotecan and SP141 individually to determine IC 50 values. Cell viability and proliferation were assessed using the MTT assay and the xCELLigence real-time monitoring system. The synergistic effects were analyzed quantitatively using the Loewe Additivity and Highest Single-Agent (HSA) models. Flow cytometry was employed to analyze cell cycle distribution, while cell death and apoptosis were monitored via high-throughput, real-time quantitative analysis using the IncuCyte live-cell kinetic imaging system.
Results: Both Topotecan and SP141 induced significant cell death in 92-1 cells. xCELLigence showed dose- and time-dependent inhibition of proliferation. Combining sub-IC 50 concentrations of topotecan and SP141 exhibited significant synergistic effects, markedly reducing growth. Cell cycle analysis revealed that topotecan causes a dose-dependent biphasic arrest in G2 and S phases, while SP141 causes G2/M arrest, leading to cell death. Cytotoxicity assays corroborated increased cell death following combination therapy, and the Caspase 3/7 assay indicated that apoptosis is the mechanism underlying cell death.
Conclusions: The multi-targeted approach combining topotecan and SP141 drugs demonstrated synergistic therapeutic effects in 92-1 cells, suggesting a potential treatment strategy for managing UM.

DOI: https://doi.org/10.64898/2026.09.23.753860