- Papillary thyroid carcinoma (PTC) is the most frequent endocrine tumor.
- Most PTC patients develop drug-resistance and progress.
- A combination of vemurafenib and palbociclib is effective in treating PTC.
Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer. It is mostly treated with the drug vemurafenib. But most PTC patients develop resistance and progress. However, a research by a Harvard Medical School team found that papillary thyroid carcinoma can be treated effectively with a combination of drugs.
Combination of drugs for stronger effect on cancer cells
In lab-grown vemurafenib-resistant thyroid cancer cells, loss of the P16 gene - which prevents cells from dividing too often - may be linked to the ability of the cancer cells to continue growing even when treated with vemurafenib.
‘A combination drug therapy using vemurafenib and palbociclib represents a novel therapeutic strategy to treat Papillary thyroid carcinoma (PTC).’
One way P16 controls cell division is by preventing the formation of a protein complex called CDK4/6, which is required for DNA to replicate inside cells. Nucera and his team wondered whether they could prevent treatment resistance by targeting the CDK4/6 complex, in effect mimicking what P16 might do. They identified palbociclib, a CDK4/6 inhibitor that was already FDA approved to treat advanced breast cancer, as a potential candidate.
When the researchers treated cells from vemurafenib-resistant, BRAFV600E-positive PTC patients with a combination of vemurafenib and palbociclib, they found that drugs acted synergistically to induce stronger cell death than when either drug was used alone.
Combined therapy with vemurafenib plus palbociclib
Interestingly, in the course of the study, the researchers also identified that the cells harbored another deleterious genetic aberration that they propose may be a novel secondary mechanism of treatment resistance in cells that are already vemurafenib-resistant. Furthermore, they confirmed that that combined therapy with vemurafenib plus palbociclib results in a very efficient strategy to target PTC cells either with primary or secondary resistance.
"Our findings suggest for the first time that a combination drug therapy using vemurafenib and palbociclib represents a novel therapeutic strategy to treat PTC," said the lead author of the study Carmelo Nucera M.D., Ph.D., an assistant professor at Harvard Medical School.
- Zeus A. Antonello1 and Nancy Hsu et al. Vemurafenib-resistance via de novo RBM genes mutations and chromosome 5 aberrations is overcome by combined therapy with palbociclib in thyroid carcinoma with BRAFV600E, Oncotargethttp://dx.doi.org/10.18632/oncotarget.21262