PARTNERSHIP OPPORTUNITIES
19 January, 2024 by Anshul (neobio)
According to GLOBOCAN 2020 data, thyroid cancer has recorded an exponential increase in the last two decades and is now the eighth most diagnosed malignancy globally. Women, in particular, show a 3-4 times higher prevalence than men. The main driving force behind this surge is presumed to be the adoption of sensitive neck ultrasound techniques, enabling the detection of small intrathyroidal tumors that would have otherwise been overlooked.
Differentiated Thyroid Cancer (DTC), including variants such as papillary, follicular subtypes and Hürthle cell variants, remains the most common type of thyroid cancer. Traditionally, surgery accompanied by radioactive iodine (RAI) therapy and thyroid hormone has been considered the standard of care. However, patients with advanced DTC, as well as those affected by anaplastic and progressive medullary thyroid cancers (ATC and MTC), often resist RAI treatment. This leaves a significant portion of thyroid cancer patients with limited treatment options, creating an urgent need for targeted therapeutics.
Targeted therapy has emerged as a ray of hope for thyroid cancer patients, particularly those with advanced stages of the disease that have not responded to traditional treatments. These therapies work by identifying and attacking specific molecular targets in cancer cells, effectively stalling their growth and spread.
Tyrosine kinase inhibitors (TKIs) are the most commonly used targeted drugs in thyroid cancer treatment. They work by blocking the enzymes that send signals for cancer cells to grow, multiply and spread.
For patients with advanced thyroid cancer who have not responded to RAI treatment, drugs like lenvatinib are promising. This drug, taken daily as a tablet for several years, has been effective in managing the disease.
Similarly, Sorafenib, the first TKI approved by the FDA for progressive metastatic DTC refractory to RAI treatment, targets Vascular Endothelial Growth Factor Receptors (VEGFR) 1-3, Platelet-Derived Growth Factor Receptor (PDGFR), and other key enzymes.
For MTC, vandetanib and cabozantinib are the commonly prescribed TKIs. These drugs have shown effectiveness in treating locally advanced or metastatic cases that are resistant to traditional treatment methods.
For ATC, a rare but aggressive form of the disease, the BRAF/MEK inhibitor combination of dabrafenib and trametinib has shown promise. This combination targets the MAPK pathway, a key player in ATC progression.
Genetic testing plays a crucial role in tailoring targeted therapy to specific genetic mutations. For instance, the drug selpercatinib targets mutations in the RET gene, which are common in certain aggressive thyroid cancers. By understanding the specific genetic landscape of a patient’s cancer, physicians can select the most effective targeted therapies. This personalized approach is central to delivering the most effective treatment and improving patient outcomes.
Targeted therapies have been a breakthrough in treating thyroid cancer. However, TKIs are known to cause fatigue, diarrhea, skin rash, bleeding, and high blood pressure. The severity of these side effects can vary among individuals. Some people may also experience changes in the functioning of their heart and kidneys. In certain cases, TKIs can cause tenderness, tingling, and blisters on the skin of the palms and soles.
Specific TKIs can also present unique adverse effects. For example, pazopanib can cause skin and hair hypopigmentation, while sorafenib can lead to skin hyperpigmentation. More severe side effects can include abnormal skin growths when treated with BRAF inhibitors dabrafenib and vemurafenib.
The rearranged-during-transfection (RET) protooncogene has emerged as a critical target in the treatment of thyroid cancer, particularly metastatic MTC. Selective RET kinase inhibitors such as LOXO-292 and BLU-667 have shown promising results in clinical trials. They have demonstrated high efficacy with minimal side effects, providing a more targeted therapeutic strategy that minimizes the severe side effects associated with TKIs. Overall, RET kinase inhibitors have exhibited response rates ranging from 47% to 62% in the treatment of metastatic MTC.
In addition to the RET kinase inhibitors, other novel therapies are also being thoroughly investigated. These include gene fusion inhibitors and immune checkpoint inhibitors. These emerging classes of medications hold the potential to revolutionize the treatment landscape of thyroid cancer, offering new hope for patients with advanced or resistant forms of the disease.
Gene fusion inhibitors target specific gene fusions that contribute to the development and progression of thyroid cancer. On the other hand, immune checkpoint inhibitors work by enhancing the body’s immune response against cancer cells. These therapies have shown promise in early clinical trials, and more comprehensive studies are underway to fully understand their efficacy and safety profiles.
The landscape of thyroid cancer treatment is rapidly evolving, offering renewed hope for patients who previously had limited options. While traditional therapies remain effective for many, the emergence of targeted therapies (e.g., TKIs, RET inhibitors, and immunotherapies) marks a significant shift toward a more personalized and precise approach to care. Though side effects remain a concern, ongoing research and advances in genetic testing are helping to match patients with therapies best suited to their specific cancer profiles. As science continues to progress, the future of thyroid cancer treatment looks increasingly optimistic.
