Pleomorphic Liposarcoma (PLPS) is a peculiar subtype of liposarcoma distinguished by its aggressive behavior and high degree of variance in its histological features. At Protheragen, we offer a comprehensive suite of preclinical services to accelerate the development of innovative therapeutics and diagnostics for pleomorphic liposarcoma (PLPS).
Overview of Pleomorphic Liposarcoma (PLPS)
Pleomorphic Liposarcoma (PLPS) is one of the most aggressive and rare forms of liposarcoma, diffused with considerable cellular pleomorphism and features of pleomorphic lipoblasts. It is regarded as one of the most aggressive types of soft tissue sarcomas due to its sophisticated histopathologic features coupled with its aggressive clinical behavior. PLPS usually develops in the extremities, especially the lower limbs, and is known to have a very high risk of local and distant metastasis as well as a high chance of local recurrence. Its histological diversity, coupled with a lack of distinct molecular markers, greatly complicates the diagnosis and therapeutic of PLPS.
Fig.1 The primary location of pleomorphic liposarcomas. (Ciongariu A. M.,
et al., 2024)
Pathogenesis of Pleomorphic Liposarcoma (PLPS)
The complete pathogenesis of plemorphic liposarcoma (PLPS) is still unclear, though it is defined by significant genetic changes. In comparison to other subtypes of liposarcoma, PLPS is devoid of recurrent genetic abnormalities. It is characterized by numerous chromosomal imbalances, including gains and deletions, and TP53 mutations, which are commonly seen and contribute to the aggressive nature of PLPS. Additionally, PLPS often lacks the MDM2 amplification seen in other liposarcoma subtypes, such as dedifferentiated liposarcoma. The genetic and molecular characteristics of PLPS, to which these somatic mutations are driving the tumor's evolution and aggressiveness, highlight the difficulty in diagnosing and managing this form of liposarcoma, reinforcing its complexity and heterogeneity.
Diagnostics Development for Pleomorphic Liposarcoma (PLPS)
- Immunohistochemistry (IHC)
Immunohistochemistry (IHC) is an essential ancillary tool in the diagnosis of PLPS. While PLPS lacks specific immunophenotypic markers, IHC can help exclude other forms of liposarcoma and carcinoma. Commonly used markers include S-100, CD34, and MDM2. However, the utility of these markers is limited due to the lack of specific expression patterns in PLPS. For instance, S-100 staining may be focal and variable, while MDM2 is typically negative in PLPS.
- Molecular Analysis
Molecular analysis is increasingly being explored for the diagnosis of PLPS. Techniques such as fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) can help identify specific genetic alterations. However, the lack of a recurrent genetic signature in PLPS limits the diagnostic utility of these methods. Nonetheless, molecular analysis remains a promising area for future diagnostic development.
Therapeutics Development for Pleomorphic Liposarcoma (PLPS)
Chemotherapy is often used in combination with surgery and radiotherapy to treat PLPS. Standard chemotherapeutic agents include doxorubicin and ifosfamide. However, the response to chemotherapy varies, and new targeted therapies are being explored to improve outcomes. For example, angiogenesis inhibitors have shown promise in some cases, but further studies are needed to establish their role in the management of PLPS.
Targeted therapies are an emerging area of research in the therapeutic of PLPS. These therapies aim to target specific molecular pathways involved in the pathogenesis of PLPS. For instance, inhibitors of the PI3K/AKT/mTOR pathway are being investigated due to the frequent activation of this pathway in PLPS. However, the lack of specific molecular targets in PLPS presents a significant challenge in the development of targeted therapies.
Table 1. Therapeutics of Pleomorphic Liposarcoma (PLPS).
| Therapeutics |
Drug Name |
Mechanism |
Description |
Stage |
| Chemotherapy |
Doxorubicin |
Inhibition of DNA synthesis |
Doxorubicin is a commonly used chemotherapeutic agent for PLPS. It works by inhibiting DNA synthesis, leading to cell death. |
Approved |
| Chemotherapy |
Ifosfamide |
Alkylation of DNA |
Ifosfamide is another chemotherapeutic agent used in combination with doxorubicin to treat PLPS. It alkylates DNA, causing cross-linking and cell death. |
Approved |
| Targeted Therapy |
Pazopanib |
Tyrosine kinase inhibition |
Pazopanib is a tyrosine kinase inhibitor that targets angiogenesis and has shown efficacy in advanced liposarcoma. |
Approved |
| Immunotherapy |
N/A |
Immune checkpoint inhibition |
Immunotherapy, including immune checkpoint inhibitors, is being explored for PLPS. These drugs enhance the immune system's ability to recognize and attack cancer cells. |
Preclinical |
| Other |
Eribulin |
Microtubule dynamics disruption |
Eribulin is a microtubule dynamics disruptor that has shown efficacy in treating metastatic PLPS. |
Approved |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen offers comprehensive services for the development of diagnostics and therapeutics for pleomorphic liposarcoma (PLPS). Our services include histopathological examination, immunohistochemistry, and molecular analysis for diagnostic development. For therapeutic development, we provide support across the drug development pipeline, from target identification and validation to lead compound screening, preclinical efficacy testing, and toxicity assessment.
Disease Models
- Primary Cell Cultures
- 3D Soft Tissue Sarcoma (STS) Organoids
- Trp53fl/fl/Rb1fl/fl/Ptenfl/fl(RPP) Mice
- Patient-Derived Xenograft Mouse Models
Protheragen understands that each research project is unique. Our customized services for PLPS diagnostics and therapeutics development are designed to meet the specific needs of our clients. Whether you require specialized histopathological analysis, tailored immunohistochemistry panels, or bespoke molecular assays, our team of experts will work with you to develop a customized research plan. If you are interested in our services, please feel free to contact us.
References
- Ciongariu, Ana-Maria, et al. ”Pleomorphic liposarcoma unraveled: investigating histopathological and immunohistochemical markers for tailored diagnosis and therapeutic innovations.” Medicina 60.6 (2024): 950.
- Wakely Jr, Paul E., Sintawat Wangsiricharoen, and Syed Z. Ali. ”Pleomorphic liposarcoma: a clinicopathologic study of 20 FNA cases.” Cancer Cytopathology 130.9 (2022): 705-713.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
