By Priyanka Reddy, Clinical Research Coordinator Associate at Stanford Medicine.
Understanding Dedifferentiated Liposarcoma
Liposarcoma is one of the most common forms of soft tissue sarcoma. There are different types, with well-differentiated liposarcoma (WDLPS) and de-differentiated liposarcoma (DDLPS) accounting for over 60% of all liposarcomas. WDLPS tends to be less aggressive with low risk of spreading, but it can sometimes turn into DDLPS which grows faster and may spread to other parts of the body.
Current Treatments
- Surgery and local radiation are the main treatments for WDLPS, as it does not respond well to chemotherapy.
- Chemotherapy can be used for DDLPS, but its effectiveness is limited with short duration. Common drugs include doxorubicin (or in combination with ifosfamide), gemcitabine (or in combination with docetaxel), trabectedin, eribulin, and pazopanib.
- Targeted therapy is being explored to block key cancer growth signals in both WDLPS and DDLPS.
Targeted Therapy
CDK4 and MDM2 are the two main genes that are amplified in WDLPS and DDLPS patients.
- CDK4/6 Inhibitors: These drugs slow cancer cell growth by blocking CDK4, a protein that helps cancer cells grow and divide. Clinical trials for palbociclib have shown to be effective in slowing progression for WDLPS and DDLPS patients and occasionally shrinking the tumor itself which is why it has become a recommended form of treatment. Another inhibitor currently undergoing clinical trials, abemaciclib, has shown promise that it may be more effective than palbociclib.
- Immune Checkpoint Inhibitors: These drugs help the immune system recognize and attack cancer cells. Clinical trial response rates for drugs like Pembrolizumab and Nivolumab have been limited for WDLPS and DDLPS patients but have shown activity. There have been additional laboratory studies which suggest that in combination with other drugs such as a CDK4/6 inhibitor, these immune checkpoint inhibitors may have enhanced efficacy. Still, further research is needed to determine the best biomarkers for WDLPS and DDLPS in order to develop more effective immune checkpoint inhibitors.
- MDM2 Inhibitors: These drugs target MDM2 which prevents the body from stopping cancer cell growth. Many clinical trials for these drugs are focused on other diseases, but there are several trials in their early stages, such as those for Milademetan and Brigimadlin, which have shown promising results for DDLPS.
Ongoing Research
While standard treatment for well-differentiated and de-differentiated liposarcoma remains limited, new targeted therapies are showing great promise. There are several ongoing and potential future clinical trials and research studies whose results are eagerly being anticipated for liposarcoma patients.