Friday, October 28, 2011
Some forms of differentiated thyroid cancer (DTC) respond to treatment with radioactive iodine, which is taken up by the thyroid gland, destroying the cancerous cells. However patients with two forms of thyroid cancer, radioiodine-refractory DTC and anaplastic thyroid cancer (ATC), do not benefit from radioiodine therapy, and other treatment options are limited.
Christine Spitzweg, MD, and colleagues from Ludwig-Maximilians-University, Munich, Germany, are exploring a novel therapeutic approach intended to modify the genetic make-up of radioiodine-refractory forms of thyroid cancer to make them more susceptible to the anti-cancer effects of radioiodine therapy. Using a non-viral genedelivery system based on nanoparticle vectors, the researchers are able to introduce the gene for the sodium iodide symporter (NIS) into radioiodine-refractory tumor cells, enhancing their uptake of therapeutic radioiodine.
The vectors contain the NIS gene, a protective polymer, and a synthetic peptide that targets the particle to an epidermal growth factor receptor (EGFR) present at varying levels on the surface of thyroid tumor cells. The researchers mixed the thyroid tumor cells with the nanoparticles. In a parallel experiment, the researchers created a similar nanoparticle complex that lacked the EGFR-specific targeting peptide.
According to data presented today at the 81st Annual Meeting of the American Thyroid Association, tumor cell lines containing higher levels of EGFR incorporated more of the nanoparticle complexes. The tumor cell lines that exhibited the most efficient nanoparticle transduction had a 7-10 fold increase in iodide uptake when the nanoparticles contained the EGFR targeting peptide compared to experiments using the complexes lacking the EGFR targeting peptide.
Preliminary tests of this therapeutic approach in mice indicate that a tumor-selective gene delivery strategy can enhance radioiodine uptake by refractory DTC and ATC tumors.
Source: American Thyroid Association
Individuals with advanced papillary thyroid cancer (PTC) that are associated with the BRAFV600E gene mutation have a higher risk of recurrent disease and progression to more advanced, poorly differentiated thyroid cancer, according to data presented today at the 81st Annual Meeting of the American Thyroid Association (ATA). An understanding of the biological processes that underlie this progression could lead to the development of more effective therapies.
One approach to studying the role of BRAFV600E in PTC initiation and progression is to create mice in which the gene mutation (BRAFV600E) has been introduced and activated in the thyroid. These transgenic mice develop advanced PTCs that closely resemble human poorly differentiated PTCs. Mabel Ryder, MD, and colleagues from Memorial Sloan-Kettering Cancer Center and the Sloan-Kettering Institute (New York, NY) used BRAFV600E transgenic mice to study the effects of tumor-associatedmacrophages (TAMs), a type of white blood cell, on PTC initiation and progression. In cancers, TAMs are versatile and can either support or inhibit cancer progression. In PTCs, BRAF activation in the thyroid is accompanied by increased levels of colony stimulating factor 1, which stimulates the recruitment of TAMs to the thyroid. Once in the thyroid, TAMs accumulate alongside cancer-associated myofibroblasts (CAMs) to form a dense layer within and around the thyroid. The researchers used genetic techniques to kill the TAMs in PTCs. The result was a significant reduction in PTC size, total tumor cell volume and a more well-differentiated, less advanced PTC. The authors also demonstrated a functional link between TAMs, the recruitment of CAMs and PTC initiation. The researchers observed that when TAMs are depleted during PTC initiation, the density of CAMs is significantly diminished along with an impairment of PTC initiation.
"Many of the new treatments for thyroid cancer, such as kinase inhibitors, aim to block the activity of oncoproteins present within tumor cells. Our data suggests that immune cells in the tumor microenvironment play an important role in the biology of these cancers. This may be clinically relevant since there are new agents in development that can target TAMs, and we believe these should be explored, particularly in patients with advanced forms of the disease," said Dr. Ryder.
Based on these findings, the researchers concluded that TAMs have an important role in the initiation and progression of PTC and may represent a potent therapeutic target for combating advanced thyroid cancers that do not respond to conventional therapies.
Source American Thyroid Association (ATA)
During surgical removal of thyroid tissue suspicious for cancer, fast, reliable, and cost-effective techniques are needed to analyze the resected tissue for biomarkers—including BRAF V600E, is a molecular biomarker for papillary thyroid cancer (PTC)—that can confirm the presence and type of cancer cells. Researchers have developed a new, rapid method for direct detection of the BRAF V600E gene in thyroid tissue without the need to purify DNA from tumor cells—high resolution melting analysis (HRM).
In HRM analysis, a sample of the resected thyroid tissue is homogenized and the DNA-containing portion is collected and washed. Polymerase chain reaction (PCR), a targeted gene detection technique, is then used to identify the presence of the BRAF V600E gene in the tissue sample. This is achieved without having to purify or sequence the DNA.
Jun Hee Park and G. Park from Chosun University Hospital, Republic of Korea, have demonstrated that HRM is at least as effective as alternative methods that rely on purified DNA for intra-operative detection of the BRAF V600E biomarker, according to data presented today at the 81st Annual Meeting of the American Thyroid Association (ATA). Using HRM to analyze cancerous tissue from 96 patients, Park and Park obtained a positive result for BRAF V600E in 58 of 96 samples (60.4%). The same 96 samples were subjected to two other testing methods that both required DNA purification—DNAsequencing and restriction fragment length polymorphism (RFLP) analysis. These analytical methods yielded a positive BRAF V600E result in 46.8% and 61.5% of samples, respectively. In comparison to these two techniques, direct HRM produced comparable results, was economical, and was suitable for intra-operative use with results available within 50 minutes.
Source: American Thyroid Association
Tuesday, October 25, 2011
(Reuters) -'s drug to treat a rare form of met the main goal of a late-stage study, prompting the company to look to an accelerated approval process that could bring the drug to market within a year.
Shares of San Francisco-based Exelixis were up 18 percent at $7.09 in heavy trading on Monday on Nasdaq. They had touched a high of $7.53 earlier in the day.
Exelixis said based on the study it was requesting permission to begin a rolling submission of data toward the marketing application of the drug cabozantinib in advanced( ).
"With the positive data, we expect cabozantinib's filing to be completed in first quarter of 2012, with potential approval in the third quarter,"analysts said in a note.
The drug significantly improved median progression-free survival (PFS) in patients suffering from MTC to 11.2 months versus 4 months for those on placebo in a trial called EXAM.
While that was lower than the numbers returned by's competing Caprelsa, Jefferies analysts said the drugs appeared comparable given that the EXAM trial appears to have enrolled more severe patients.
About 44,600 new thyroid cancer cases were diagnosed in the United States during 2010, and about 1,690 people died from the disease, according to the National Cancer Institute.
Cabozantinib, which is also being tested forand castration-resistant prostate cancer (CRPC), is an oral drug designed to limit blood supply to tumors and block two segments of a pathway used by cancer cells to grow and spread.
In June, Exelixis reported data from a clinical trial showing cabozantinib led to significant tumor shrinkage in several different types of solid tumors, including 24 percent of patients with metastatic ovarian cancer, but also caused the deaths of six patients.
The EXAM trial is being conducted under a special protocol assessment (SPA) agreement, which guarantees that the design and analysis of the trial are adequate to support a marketing application submission to the U.S. Food and Drug Administration.
(Reporting by Esha Dey and Kavyanjali Kaushik in Bangalore; Editing by Roshni Menon and Supriya Kurane)
Friday, October 14, 2011
Thursday, October 6, 2011
For some people, cancer is a one-time event. They go through treatment and recovery, and the disease does not return. For others, cancer may not ever fully disappear. Their cancer may respond to treatment and then come back, or treatment may simply keep it from growing and spreading. For people living with cancer, it's important to understand what it means when cancer doesn't go away – and how remission and recurrence may be part of your cancer journey.
|Facing the same cancer more than once can be a frustrating and exhausting experience. Learn how you can better cope with the effects of recurring cancer here.|
When a cancer comes back after treatment, it is known as cancer recurrence. The cancer sometimes returns at the same spot (known as local recurrence) or it may show up in parts of the body that were not previously affected. Some types of cancers, such as ovarian cancer, are more likely to return than others. People with recurring cancer may need multiple rounds of treatment or they may need to change the type of treatment they receive.
Remember that even when a cure is not possible, treatment may help keep cancer at bay. If you have cancer that does not go away, talk to your doctor about what options may be right for you.