The most common subtype of renal cell carcinoma (RCC), clear cell RCC (ccRCC), occurs in more than three quarters of RCC patients. Nearly a third of those patients present with metastasis at the time of diagnosis, and another third develop either local recurrence or distant metastases even after the initial treatment. The five-year survival rate of patients with advancestage ccRCC remains at a devastatingly low 10%. A distinguishing characteristic of ccRCC is a highly vascularized tumor microenvironment due to upregulation of pro-angiogenic factor VEGF. While targeting VEGF and other pro-angiogenic signaling pathways tends to yield positive results initially, virtually all patients eventually develop resistance to current treatments.
Description
Profilin1-actin interaction is critical for actin-driven biological processes; specifically, angiogenesis, which drives ccRCC in addition to other pathologies including proliferative diabetic retinopathy, wet age-related macular degeneration, and other types of cancer. Targeting Profilin1 instead of VEGF is an alternative strategy to treating these diseases without developing the spontaneous or acquired resistance seen in anti-VEGF approaches. Proof-of-concept studies have demonstrated that inhibiting the Profilin1-actin interaction reduces proliferation and migration of RCC tumor cells and may also prove useful as a prognostic biomarker.
Applications
- Treating clear cell renal cell carcinoma
- Treating other angiogenesis-driven diseases such as proliferative diabetic retinopathy, wet age-related macular degeneration, and other cancers
Advantages
- Better inhibition at lower concentrations compared to other profilin1-actin inhibitors
- Avoids risk of development of resistance to anti-VEGF therapies
- Found to be non-toxic in vivo
Invention Readiness
In vivo data; SAR studies of commercially available structural analogs underway
IP Status
https://patents.google.com/patent/US20230293490A1
