Researchers identify novel therapeutic strategy for drug-resistant thyroid cancers

October 18, 2017, Impact Journals

Perhaps the only thing more devastating than being diagnosed with cancer is to find out after a period of remission that the cancer has become drug-resistant and progressed to an incurable state. This is the unfortunate fate for many patients with papillary thyroid carcinoma (PTC), the most common form of thyroid cancer, who are treated with the drug vemurafenib. However, new findings by a Harvard Medical School team suggest that palbociclib, a drug that is FDA-approved to treat advanced breast cancer, may be able to overcome vemurafenib resistance in PTC. Their results were published today on the cover for Oncotarget.

The genetic hallmark of PTC is a specific mutation in the BRAF gene. Patients presenting with the "BRAFV600E" mutation, as it is referred to, are often treated with drugs like vemurafenib, which selectively target this mutation. However, most patients that initially respond to treatment eventually develop resistance, allowing the to grow and spread.

"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 lead author of the study Carmelo Nucera M.D., Ph.D., an assistant professor at Harvard Medical School.

Previous research by this team had shown that in lab-grown vemurafenib-resistant thyroid cancer , 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.

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 , 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.

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 in cells that are already vemurafenib-resistant. Furthermore, they confirmed that that combined therapy with plus palbociclib results in a very efficient strategy to target PTC cells either with primary or secondary resistance.

"Our results support the proof of concept that this combined therapy can be tested in a clinical trial of patients with metastatic ," said Nucera.

Explore further: Adding vemurafenib doubles progression-free survival in BRAF metastatic colorectal cancer

More information: Zeus A. Antonello 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, Oncotarget (2017). DOI: 10.18632/oncotarget.21262

Related Stories

Adding vemurafenib doubles progression-free survival in BRAF metastatic colorectal cancer

June 5, 2017
Clinical trial results presented in an oral abstract session 3:00pm Monday, June 5 at the American Society for Clinical Oncology (ASCO) Annual Meeting 2017 shows promising results for the addition of vemurafenib (anti-BRAF) ...

Potential treatment for brain cancer as drug shrinks tumours

August 14, 2017
An international team of researchers has found a drug previously approved to treat breast cancer could also be used to shrink medulloblastoma, a common form of childhood brain tumour.

New colorectal cancer targeted therapy combination shows promise

January 18, 2017
New SWOG study results show significantly better outcomes for patients with a treatment-resistant form of metastatic colorectal cancer when the BRAF inhibitor vemurafenib is added to a standard treatment. The findings, for ...

Study shows biomarkers can predict which ER-positive breast cancer patients respond best to first-line therapy

June 27, 2017
Two challenges in treating patients with estrogen-positive breast cancer (ER+) have been an inability to predict who will respond to standard therapies and adverse events leading to therapy discontinuation. A study at The ...

New drug, Vemurafenib, doubles survival of metastatic melanoma patients

March 1, 2012
A report published this week in the New England Journal of Medicine shows that the 50 percent of metastatic melanoma patients with a specific genetic mutation benefit from the drug Vemurafenib – increasing median survival ...

Researchers find potential solution to melanoma's resistance to vemurafenib

February 28, 2012
Researchers at Moffitt Cancer Center in Tampa, Fla., and colleagues in California have found that the XL888 inhibitor can prevent resistance to the chemotherapy drug vemurafenib, commonly used for treating patients with melanoma.

Recommended for you

Ovarian cancer genetics unravelled

August 14, 2018
Patterns of genetic mutation in ovarian cancer are helping make sense of the disease, and could be used to personalise treatment in future.

Lymphatic vessels unexpectedly promote the spread of cancer metastases

August 14, 2018
Lymphatic vessels actively contribute to the spread of cancer metastases from various organs. This unexpected realisation is the result of a joint study by researchers from ETH Zurich and the University Hospital Zurich as ...

Large collection of brain cancer data now easily, freely accessible to global researchers

August 14, 2018
A valuable cache of brain cancer biomedical data has been made freely available to researchers worldwide, say researchers at Georgetown Lombardi Comprehensive Cancer Center. The dataset, REMBRANDT (REpository for Molecular ...

Researchers uncover a major new vulnerability of childhood leukemia

August 14, 2018
Childhood leukemia is a diagnosis that no family ever wants to endure. While the treatment of most types of leukemia has improved steadily over the years, a few specific types remain very difficult to treat. One of these ...

Rare cancer could be caught early using simple blood tests

August 14, 2018
A pioneering study into myeloma, a rare cancer, could lead to GPs using simple blood tests to improve early diagnosis.

First study on physical properties of giant cancer cells may inform new treatments

August 13, 2018
Polyploidal cancer cells—cells that have more than two copies of each chromosome—are much larger than most other cancer cells, are resistant to chemotherapy and radiation treatments and are associated with disease relapse. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.