Although it is not the most common form of skin cancer, melanoma causes the majority of skin cancer-related deaths. Approximately 160,000 new cases of malignant melanoma are diagnosed each year worldwide, and incidence and mortality rates in light-skinned populations continue to rise. Inhibitors of RAF protein kinases, which are key components of cellular signal transduction pathways, have been suggested for use in disrupting tumor cell growth in melanoma patients. However, some subjects develop secondary resistance to BRAF inhibitors, and tumor regression is only temporary. Treating cancer by inhibiting RAF kinases will require agents that augment the effect of BRAF inhibitors and limit secondary resistance.
This figure shows the potency of Grp94-specific antibody W9 combined with a BRAF inhibitor (BRAFI) in inhibiting the migration and spread of tumor cells compared to controls with human Ig and BRAFI, BRAFI alone, W9 alone, and human Ig alone. (* refers to a p value of < 0.05, ** to a p value of < 0.01).
Description
Researchers at the University of Pittsburgh have found that glucose regulated protein (GRP)94-specific antibodies synergistically combines with BRAF inhibitors to decrease migration of melanoma cells resistant to BRAF inhibitors when the tumor cell expresses GRP94 on its surface. The mAb-defined GRP94 epitope is selectively expressed on malignant cells but is not detectable on normal cells, thus rendering no or very limited side effects. Administration of mAbs increases and restores the sensitivity of BRAF-I in melanoma cells that have acquired resistance is a promising step towards overcoming secondary resistance.
Applications
• Preventing metastasis
• Decreasing the number of micro-metastases
• Treating melanoma, including spreading melanoma, nodular melanoma, acral lentiginous melanoma, and lentigo maligna
• Treating other cancers, such as breast cancer, prostate cancer, ovarian cancer, thyroid cancer, colon cancer, stomach cancer, pancreatic cancer, glioma, chordoma, chrondrosarcoma, glioma, or squamous cell carcinomas
Advantages
Effective in mitigating tumor metastasis without developing resistance to BRAF inhibitor
Invention Readiness
In vitro
IP Status
https://patents.google.com/patent/US8771687B2
