Targeted and immuno-based therapies in sarcoma: mechanisms and advances in clinical trials

Tang, Fan; Tie, Yan; Wei, Yuquan; Tu, Chongqi; Wei, Xiawei

doi:10.1016/j.bbcan.2021.188606

Cited by 27 publications

(26 citation statements)

References 390 publications

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“…Given the rarity and significant heterogeneity of OS, along with the challenges associated with recruiting an adequate patient population for clinical trials, [ 35 ] it becomes essential to optimize preclinical research models.…”

Section: Resultsmentioning

confidence: 99%

Numbers Matter: The Role of Cell Dose in the Treatment of Osteosarcoma Using Mesenchymal Stromal Cells as Cellular Vehicles

Martella

Dozza

Ferroni

et al. 2023

Advanced Therapeutics

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A promising approach enhancing osteosarcoma (OS) prognosis involves the combination of various techniques, such as chemo‐ and photodynamic therapy, delivered through nanocarriers for synergistic cell death. Among the potential candidates for improving drug accumulation at the tumor site, mesenchymal stromal cells (MSCs) exhibit a significant advantage due to their tumor‐homing ability and intracellular drug retention. This study evaluates the efficacy of chemo‐releasing and photoactive bimodal nanoparticles, kPCe6 NPs, delivered via MSCs. In vitro analyses show that cells internalize and retain kPCe6 NPs in a dose‐dependent manner and that kPCe6‐loaded cells induce massive tumor cell death in a tridimensional tumor model. Results from an in vivo orthotopic OS murine model show negligible tumor cell death upon peritumoral administration of two doses containing 106 loaded cells. To gain insight into this observation, this work investigates the role of cell dose in treatment efficacy. The results indicate that achieving a tumor reduction higher than 90% requires a substantial number of loaded cells, approximately 35% of the entire tumor mass, highlighting the criticality of the cell dose for the success of this therapeutic approach and its potential impact on clinical translation in OS patients, particularly when the number of tumor cells is limited.

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Section: Resultsmentioning

confidence: 99%

Numbers Matter: The Role of Cell Dose in the Treatment of Osteosarcoma Using Mesenchymal Stromal Cells as Cellular Vehicles

Martella

Dozza

Ferroni

et al. 2023

Advanced Therapeutics

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“…However, the development of genome sequencing and targeted drugs bring sarcoma therapy to precision times. Some new therapies have been used to treat osteosarcoma, such as anti-angiogenesis therapy, molecular targeted therapies, immune-based therapies, etc., which have improved the prognosis of patients with osteosarcoma ( 22 ). Combined with these methods, the efficacy of neoadjuvant chemotherapy for TOS is expected to be improved.…”

Section: Discussionmentioning

confidence: 99%

Prognostic analysis of telangiectatic osteosarcoma of the extremities

et al. 2023

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Background and objectivesTelangiectatic osteosarcoma (TOS) is a rare but highly malignant subtype of osteosarcoma. Although surgical treatment is the primary treatment modality for osteosarcoma, evidence on the benefits of different surgical methods in patients with TOS is lacking. This study aimed to compare the effects of different surgical and adjuvant treatments on overall survival of TOS, and the association of patient demographics, oncological characteristics, and socioeconomic status on treatment outcomes.MethodThis retrospective study selected the most common TOS cases of the extremities registered in the Surveillance, Epidemiology, and End Results (SEER) database from 1989 to 2019. Univariate and multivariate Cox regression models were used to analyze all prognostic factors, and Kaplan-Meier analyses were performed for disease-specific treatment factors of survival.ResultA total of 127 patients were included in the analysis. The average age at initial diagnosis was 20.09 years. In univariate analyses, the absence of metastasis at initial diagnosis, limb-salvage surgery, adjuvant chemotherapy, and no regional lymph node dissection were associated with a lower risk of death. Multivariate analysis further showed that the presence or absence of distant metastasis and regional lymph node dissection, implementation of adjuvant chemotherapy, and choice of surgical method were independent predictors of prognosis.ConclusionDistant metastasis and regional lymph node dissection are associated with poorer outcomes in TOS, and amputation has no better prognosis than limb salvage surgery. Compared with conventional chemotherapy, neoadjuvant chemotherapy did not significantly improve the prognosis of TOS.

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“…Therefore, the combination of drugs targeting the pro-oncogenic role of EZH2 in tumoral cells and its role promoting an immunosuppressive TME, with immunotherapy, could have a synergistic effect, improving the therapeutic responses of some types of cancer. Despite preclinical studies in hepatocellular carcinoma [ 279 ], PCa [ 208 ], head and neck cancer [ 280 ] and Ewing sarcoma [ 281 ] showing that the combination of EZH2 inhibitors and CPIs has a synergistic effect, there are no studies investigating the immunological consequences of these combinations. EZH2 activity is fundamental to maintaining body homeostasis and to the development of different cells, including lymphoid cells, performing critical immune effector functions against tumors.…”

Section: Discussionmentioning

confidence: 99%

Polycomb Directed Cell Fate Decisions in Development and Cancer

Germán

Ellis

2022

Epigenomes

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The polycomb group (PcG) proteins are a subset of transcription regulators highly conserved throughout evolution. Their principal role is to epigenetically modify chromatin landscapes and control the expression of master transcriptional programs to determine cellular identity. The two mayor PcG protein complexes that have been identified in mammals to date are Polycomb Repressive Complex 1 (PRC1) and 2 (PRC2). These protein complexes selectively repress gene expression via the induction of covalent post-translational histone modifications, promoting chromatin structure stabilization. PRC2 catalyzes the histone H3 methylation at lysine 27 (H3K27me1/2/3), inducing heterochromatin structures. This activity is controlled by the formation of a multi-subunit complex, which includes enhancer of zeste (EZH2), embryonic ectoderm development protein (EED), and suppressor of zeste 12 (SUZ12). This review will summarize the latest insights into how PRC2 in mammalian cells regulates transcription to orchestrate the temporal and tissue-specific expression of genes to determine cell identity and cell-fate decisions. We will specifically describe how PRC2 dysregulation in different cell types can promote phenotypic plasticity and/or non-mutational epigenetic reprogramming, inducing the development of highly aggressive epithelial neuroendocrine carcinomas, including prostate, small cell lung, and Merkel cell cancer. With this, EZH2 has emerged as an important actionable therapeutic target in such cancers.

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Targeted and immuno-based therapies in sarcoma: mechanisms and advances in clinical trials

Cited by 27 publications

References 390 publications

Numbers Matter: The Role of Cell Dose in the Treatment of Osteosarcoma Using Mesenchymal Stromal Cells as Cellular Vehicles

Numbers Matter: The Role of Cell Dose in the Treatment of Osteosarcoma Using Mesenchymal Stromal Cells as Cellular Vehicles

Prognostic analysis of telangiectatic osteosarcoma of the extremities

Polycomb Directed Cell Fate Decisions in Development and Cancer

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