One of the most commonly seen manifestations of Thyroid Cancer is Papillary Thyroid Carcinoma (PTC), a form the cancer grows at the base of the neck. Unfortunately, treatment of this tumor often leads to diminishing returns as patients build up resistance to medication. A joint study by Harvard Medical School and the University of Parma in Parma, Italy found that administering two different drugs at once had synergistic effects that resulted in more cell death than any single medication could manage while also overcoming the diminishing returns.
Listen to the breakdown of the study here: https://soundcloud.com/oncotarget/oncotarget-combined-therapy-with-vemurafenib-and-palbociclib
Papillary Thyroid Carcinoma’s Root Cause
Cancer emerges in patients due to cell mutations. PTC is linked to a specific mutation in the BRAF gene, known as BRAFV600E, and is often treated with drugs like vemurafenib that specifically target the mutation. However, it turns out that administering vemurafenib results in a side effect – the loss of the P16 gene, an essential gene which governs the formation of proteins required for cell division. Typically, the P16 will block the creation of these proteins during certain phases of cell reproduction or if certain criteria are not fulfilled. The loss P16 in genes with the BRAFV600E mutation sees the downstream effect of unmitigated and uncontrolled cell replication. In other words, the loss of P16 in cancer cells is a long-term side effect of administering vemurafenib that can cause cancer to continue growing.
Minimizing PTC Cell Mutations
To mitigate the effects of losing P16, the research team looked to mimic the actions of P16 in an attempt to regulate uncontrolled growth. In a cell, P16 controls the rate of cell division by preventing the formation of the CDK4/6 protein complex, an essential building block from DNA replication. The team looked to slow the formation of CDK4/6, even when P16 mutated to allow unmitigated replication of the protein, and the team found an existing drug Palbociclib. Palbociclib is a CDK4/6 inhibitor already approved by the FDA for treating advanced breast cancer.
Researchers tested the effects of administering both vemurafenib and palbociclib in PTC cells and they found that the two drugs had a synergistic effect – the combination lead to greater cell death than if either drug was used alone. The combination of drugs targets the PTC cancer cells through multiple avenues and will lead to slower growth of drug resistance, simply by virtue of drugs being removed much more efficiently. These findings are notable because researchers also identified a number of other secondary resistances that can be exploited to make more effective treatment options.
Oncotarget is a peer-reviewed open access medical journal that covers all aspects of oncology as well as additional topics including Immunology, Microbiology, Autophagy, Pathology, Aging, and more. The journal is published two times a week on Tuesdays and Fridays.