Thyroid Cancer – Diagnosis, Symptoms, and Treatment and Exelixis

Exelixis

 

The thyroid gland, shaped like a butterfly, sits just below the skin and several thin muscle layers in the lower part of the neck. It’s attached to the deeper neck structures (trachea and voice box) and elevates when we swallow. The thyroid gland secretes hormones that control a variety of systems all through out life including our metabolism, growth and development. Each year about 30,000 Americans are diagnosed with thyroid cancer. It is about 2 to 4 times more common in women than in men, and is most prevalent between ages 25 and 65.

Thyroid cancer prognosis can occur during a routine physical exam. Your doctor may ask you about your medical history and can recommend screening tests for thyroid cancer before any symptoms appear.
Thyroid cancer symptoms usually begin as a lump or swelling in the neck, called a nodule. Thyroid nodules are very common (12% of general population) and most are benign. All nodules, however, need to be carefully evaluated as a very high percentage of nodules are cancerous (10-15%).

If you have a lump or nodule in your thyroid, your doctor may order a CT scan or an ultrasound to get a better look at your thyroid. If your doctor thinks that the lump or nodule could be cancerous, he or she will do a biopsy of the thyroid gland which involves removing a piece of your thyroid, often through a needle. This test is a simple procedure that can be done in your doctor’s office.

Tests which may be done before, during, or after any thyroid cancer treatment may include specific blood tests, CT scans, chest X-rays, thyroid ultrasounds, or radioactive iodine scans, which help determine whether the cancer has spread to other parts of the body. In rare cases, when thyroid cancer has significantly spread, an MRI or a PET scan may be done.

Most thyroid cancers are very treatable and carry a high cure rate, especially when discovered early. Treatment of thyroid cancer requires a close collaboration between endocrinologists and thyroid surgeons. The treatment plan by our team of doctors is always decided through this collaboration. The first and most effective step in treatment of thyroid cancer is usually surgery. Thyroid cancer surgery involves removal of a portion (hemi-thyroidectomy) or the entire thyroid gland (total thyroidectomy).

The newest advances in the field of surgery (endoscopes and endoscopic instruments) allow for minimally invasive thyroidectomy (Endoscopic Assisted Thyroidectomy, E.A.T.™) (as small as 2.5 cm or close to an inch), rather than the standard technique using a large incision and greater tissue trauma. This is a revolutionary way of surgically treating the thyroid, and because it involves a much smaller incision, it enables patients to go home the same day, with less scarring and quicker recovery time.

Facts about the thyroid cancer drug cabozantinib

IMPLICATION OF VEGF-R/KDR/MET INHIBITION IN CANCERS AND XL880:

Many cancers harbor overexpressed Met receptor tyrosine kinase (MTK), its ligand hepatocyte growth factor (HGF) and its interacting protein vascular endothelial growth factor (VEGF) receptors (VEGF-Rs) like Kinase insert domain receptors (KDRs) that contribute to tumor progression. Inhibiting these receptors using a small molecule inhibitor seems to be an attractive approach in treating cancer cells and XL880 MET inhibitor does the same. The XL880 VEGFR inhibitor is also known as Foretinib or EXEL-2880 (as it was discovered by the company Exelixis) or GSK1363089 or GSK089 (as now XL880 KDR inhibitor is being developed by GlaxoSmithKline). XL880 structure shows it to be a dicarboxamide derivative. XL880 prices are on the higher side and one can buy XL880 10 mg vial from XL880 suppliers for $250. XL880 solubility can be gained in DMSO and XL880 stability is for 2 years when stored at -20oC. XL880 IC50 for an effective MET and KDR inhibition is 0.4 nM and 0.8 nM, respectively.

PRECLINICAL ASSESSMENT OF XL880:

In human tumor cell lines the MET+ but HER1– or HER2– amplification combination provides sensitivity to XL880 alone, while MET+ with HER1+ and HER2+ amplification makes cells more susceptible towards the combination of XL880 with Erlotinib or Lapatinib. Similarly in gastric cancer cells a MET+ but FGFR2– amplification combination makes these cells sensitive towards XL880 treatment. Another report cited the contribution of AXL overexpression to XL880 sensitivity in chemotherapy resistant cancer cells. In genetic adenocarcinoma murine model, XL880 treatment inhibited c-Met activation and prevented the progression of these tumors from primary stage to invasive stage along with decreasing their tumor size and metastatic abilities.

CLINICAL SUCCESS OF XL880:

The first MET inhibitor in clinics, XL880 clinical trials show that it is well tolerated in patients. XL880 inhibits anchorage-independent increase of tumor cells under both normoxic or hypoxic conditions to result in tumor regression. XL880 phase I clinical trials show good tolerance at clinically relevant doses, which was assessed in a phase I clinical trial to be 240 mg and was used in various XL880 phase II trials. Promising partial responses were obtained in advanced solid tumors patients in a phase I study. A phase II clinical trial in head and neck cancer patients (NCT00725764) showed 65% patients to gain a stable disease after an year of XL880 treatment. Various clinical trials by GlaxoSmithKline like a phase II study assessed the safety profile, response and tolerance of XL880 in papillary renal cell carcinoma patients (NCT00726323) and in advanced hepatocellular carcinoma (liver cancer) patients (NCT00920192). Some NCIC studies like a phase II trial is implementing XL880 against “triple negative” breast cancer (SB 203580). Another NCIC phase I study determined the safe and clinically relevant dose of XL880 and Lapatinib co-treatment in breast cancer patients to assess the efficacy in terms of survival outcome of this combination in comparison with Lapatinib as a single agent (VX-222).

Article Contributors: advancedonc and Neuro

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