Molecular mechanisms underpinning sarcomas and implications for current and future therapy

@article{Damerell2021MolecularMU,
  title={Molecular mechanisms underpinning sarcomas and implications for current and future therapy},
  author={Victoria Damerell and Michael Sean Pepper and Sharon Prince},
  journal={Signal Transduction and Targeted Therapy},
  year={2021},
  volume={6}
}
Sarcomas are complex mesenchymal neoplasms with a poor prognosis. Their clinical management is highly challenging due to their heterogeneity and insensitivity to current treatments. Although there have been advances in understanding specific genomic alterations and genetic mutations driving sarcomagenesis, the underlying molecular mechanisms, which are likely to be unique for each sarcoma subtype, are not fully understood. This is in part due to a lack of consensus on the cells of origin, but… 

Immunotherapy in soft tissue and bone sarcoma: unraveling the barriers to effectiveness

TLDR
An up-to-date overview of the different immunotherapy modalities as potential treatments for sarcoma is provided, to identify barriers posed by the Sarcoma microenvironment to immunotherapy, highlight their relevance for impeding effectiveness, and suggest mechanisms to overcome these barriers.

Complex Elucidation of Cells-of-Origin in Pediatric Soft Tissue Sarcoma: From Concepts to Real Life, Hide-and-Seek through Epigenetic and Transcriptional Reprogramming

TLDR
How cellular reprogramming mediated by driver genes in STS can profoundly reshape the molecular and morphological features of a transformed cell and lead to erroneous interpretation of its cell-of-origin is discussed.

The c-Myc/TBX3 Axis Promotes Cellular Transformation of Sarcoma-Initiating Cells

TLDR
The data described indicate that the c-Myc/TBX3 oncogenic molecular pathway may be a key mechanism that transforms hMSCs into sarcomas.

Targeting the oncogenic TBX3:nucleolin complex to treat multiple sarcoma subtypes.

TLDR
These findings provide the first evidence thatTBX3 requires nucleolin to promote features of sarcomagenesis and that disruption of the oncogenic TBX3-nucleolin interaction by AS1411 may be a novel approach for treating sarcomas.

Myxofibrosarcoma landscape: diagnostic pitfalls, clinical management and future perspectives

TLDR
An overview of current diagnostic pitfalls and clinical management of MFS is provided and a look at future directions will be discussed.

Pan-sarcoma characterization of lncRNAs in the crosstalk of EMT and tumour immunity identifies distinct clinical outcomes and potential implications for immunotherapy.

TLDR
By integrative analysis on multi-omics profiling, the findings provide a comprehensive resource for understanding the functional role of lncRNA-mediated immune regulation in sarcomas, which may advance the understanding of tumour immune response and the development of lNCRNA-based immunotherapeutic strategies for sarcoma.

Established and Experimental Systemic Treatment Options for Advanced Liposarcoma

TLDR
Surgical resection is the mainstay of treatment for patients with localized liposarcoma, and results from trials exploring experimental therapeutic options will further define the role that these new treatments will play in the management of the different subtypes of liposARcoma.

Enapotamab Vedotin, an AXL-Specific Antibody-Drug Conjugate, Demonstrates Antitumor Efficacy in Patient-Derived Xenograft Models of Soft Tissue Sarcoma

TLDR
This study provides a preclinical rationale for the evaluation of AXL-targeting ADCs in the treatment of A XL-expressing sarcomas and demonstrated significant tumor growth delay, regression, and/or prolonged survival compared to isotype control ADC in 5/8 STS PDX models investigated.

Cancer Therapy Guided by Mutation Tests: Current Status and Perspectives

TLDR
The invention of genomically tailored treatment has resulted in a spectacular improvement in disease outcomes for a significant portion of cancer patients, and there is an increasing utilization of agnostic testing which involves the analysis of all potentially actionable genes across all tumor types.

References

SHOWING 1-10 OF 333 REFERENCES

CDKs in Sarcoma: Mediators of Disease and Emerging Therapeutic Targets

TLDR
Assessment of the prevalence and importance of CDK pathway alterations in sarcomas, highlighting the gap in knowledge for certain CDKs in these tumors, and insight into studies focused on CDK inhibition for sarcoma treatment are provided.

Modeling sarcomagenesis using multipotent mesenchymal stem cells

TLDR
The existing MSC-based models of sarcoma are reviewed and the most common mechanisms leading to tumoral transformation of MSCs and sarcomagenesis are discussed, which will be undoubtedly valuable in providing a better understanding about the etiology and pathogenesis of mesenchymal cancer.

Mechanisms of sarcomagenesis.

Osteosarcoma: Cells-of-Origin, Cancer Stem Cells, and Targeted Therapies

TLDR
Current OS cell-of-origin models, the properties of the OS-CSC and its niche, and potential new therapies able to target OS- CSCs are recapitulates.

Targeting the undruggable: exploiting neomorphic features of fusion oncoproteins in childhood sarcomas for innovative therapies

TLDR
A broad overview of the current literature on targeting neomorphic features of fusion oncogenes found in Ewing sarcoma, alveolar rhabdomyosarcomas, and synovial sarcomas is provided, and a perspective for future developments is given.

Preclinical In Vivo Modeling of Pediatric Sarcoma—Promises and Limitations

TLDR
This review of available approaches to model sarcoma in vivo focused on genetically engineered and patient-derived mouse models, compared strengths and weaknesses, and finally explored possibilities and limitations to utilize these models to advance both biological understanding as well as clinical diagnosis and therapy.

Osteosarcoma: Molecular Pathogenesis and iPSC Modeling.

Notch signaling in pediatric soft tissue sarcomas

TLDR
An outline of recently gathered evidence on the role of Notch signaling in soft tissue sarcomas is presented, highlighting its importance in tumor cell biology.

Molecular pathology of sarcomas.

TLDR
This review points out the clinical projection of sarcomagenesis elucidation and knowledge of diverse types of molecular alterations in sarcomas, as well as the identification of reliable molecular markers and possible therapeutic targets.
...