Neuroendocrine cancers involve malignant cells that occur anywhere within the body’s neuroendocrine system, which includes the thyroid, adrenal, pancreas, parathyroid and pituitary glands.
More than 60,000 people were diagnosed with thyroid cancer in the United States in 2013, but other types of endocrine cancer are rare. Tumors found in other endocrine glands are not uncommon, but they are almost always benign. Cancerous tumors spread by invading neighboring or distant tissue, but benign tumors do not spread.
Because endocrine glands normally secrete hormones, tumors within these glands may also secrete hormones, often in abnormal amounts. However, secreting hormones does not make a tumor benign or cancerous. This feature is determined solely by the tumor’s capacity to spread from its original position.
At the OSUCCC – James, experts in this highly specialized field are dedicated to supporting and caring for patients with endocrine cancers and their families. Our team approach provides the best research and science-based treatment, putting our physicians and researchers on the leading edge of advances in detecting and treating these malignancies.
- Evaluating new targeted therapies for endocrine cancers
- Designing innovative clinical trials that efficiently combine novel and standard anticancer agents for endocrine cancers and their complications
- Applying translational and basic science findings to develop more effective therapies for endocrine cancers
The Ohio State University and MD Anderson Cancer Center Thyroid Cancer SPORE (Specialized Program of Research Excellence) (P50 CA168505)
PI: Matthew Ringel, MD
- Improve the outcomes and lives of patients with thyroid cancer by identifying genetically "at-risk" individuals, thus allowing for early diagnosis and prediction of tumor behavior
- Develop new approaches to minimize side effects of treatments
- Develop better biomarkers and treatment options for progressive, metastatic disease
Genetic and Signaling Pathways in Epithelial Thyroid Cancer (5 P01 CA124570 07)
PI: Matthew Ringel, MD
- Functionally characterize genes that predispose to papillary thyroid cancer (PTC) in families identified in the previous cycle of this P01 grant and apply new technologies to a larger number of families to identify more genes that predispose to PTC
- Extend the work, using a candidate gene approach for follicular thyroid cancer (FTC) and PTC risk that has identified interactions between signaling pathways
- Design approaches to enhance 1-131 therapy, using novel mouse imaging techniques developed in the previous P01 cycle and extend that work to identify other unknown regulators of this process
- Determine the role and potential therapeutic importance of p21-activated kinase (PAK), a newly identified signaling pathway downstream of BRAF, in thyroid cancer in vivo, and determine its role in resistance to RAF inhibitors
PKA and Follicular Thyroid Carcinogenesis: Roles of Interacting Pathways (5R01CA170249-02)
PI: Lawrence Kirschner, MD, PhD
- Identify non-PKA pathways activated by thyroid-stimulating hormone (TSH) that suppress PKA's ability to produce thyroid cancers
- Elucidate the molecular basis by which inactivation of Prkar1a combines with loss of Pten to produce an aggressive, metastatic follicular thyroid cancer (FTC) phenotype; this will include examining a cohort of human FTC to determine if similar signaling alterations are observed
- Build on preliminary data from mouse and human FTCs indicating that mTOR activation occurs during carcinogenesis; characterize FTC-specific isoforms of the mTOR protein and its partners and probe the mechanism of mTOR activation
- Use these data to drive molecular analysis of these processes in a large cohort of human tumors
- Gain insights into the biology of FTCs and help pave the way for developing treatments
(OSU-14291) Randomized Double-Blind Phase II Study of Radioactive Iodine (RAI) in Combination with Placebo or Selumetinib for the Treatment of RAI-Avid Recurrent/Metastatic Thyroid Cancers (NCT02393690)
PI: Jennifer Sipos, MD
- Determine the response rate at 6 months following treatment with 131I (iodine I-131) in combination with placebo or selumetinib for radioactive iodine-avid (RAIA) recurrent and/or metastatic thyroid cancer
(OSU-15245) A Multicenter, Randomized, Double-Blind Phase 2 Trial of Lenvatinib (E7080) in Subjects With 131I-Refractory Differentiated Thyroid Cancer (NCT02702388)
PI: Manisha Shah, MD
- Evaluate Whether an Oral Starting Dose of 18 mg Daily Will Provide Comparable Efficacy to a 24-mg Starting Dose, But Have a Better Safety Profile
(ALLIANCE-A091302) Randomized Phase II Study of Sorafenib with or without Everolimus in Patients with Radioactive Iodine Refractory Hürthle Cell Thyroid Cancer (NCT02143726)
PI: Bhavana Konda, MD, MPH
- Compare the progression free survival between sorafenib and everolimus versus sorafenib alone in patients with radioactive iodine refractory Hurthle cell thyroid cancer
- Compare the confirmed response rate, overall survival and adverse event rates between sorafenib and everolimus versus sorafenib alone
(ECOG-ACRIN-EA2142) Randomized Phase II Study of Platinum and Etoposide versus Temozolomide and Capecitabine in Patients with Advanced G3 Non-Small Cell Gastroenteropancreatic Neuroendocrine Carcinoma (NCT02595424)
PI: Manisha Shah, MD
- Assess the progression free survival (PFS) of platinum (cisplatin or carboplatin) and etoposide versus the PFS of temozolomide and capecitabine in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas
- Assess the response rate (RR) of platinum (cisplatin or carboplatin) and etoposide versus the RR of temozolomide and capecitabine in patients with advanced G3 non-small cell gastroenteropancreatic neuroendocrine carcinomas
(ECOG-ACRIN-EA2161) A Phase II Study of MLN0128 (TAK-228) in Rapalog-Resistant Advanced Pancreatic Neuroendocrine Tumors (PNET) (NCT02893930)
PI: Manisha Shah, MD
- Evaluate overall response rate associated with sapanisertib (MLN0128 [TAK-228]) in patients with advanced pancreatic neuroendocrine tumors (PNETs)
- Evaluate progression-free survival (PFS) associated with MLN0128 (TAK-228) in patients with advanced pancreatic neuroendocrine tumors (PNETs)
(OSU-1710) A Phase 1 Study of Oral LOXO-292 in Adult Patients with Advanced Solid Tumors, Including RET-Fusion Non-Small Cell Lung Cancer, Medullary Thyroid Cancer, and Other Tumors with Increased RET Activity (NCT03157128)
PI: Manisha Shah, MD
- Evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of LOXO-292 administered orally to patients with advanced solid tumors, including RET-fusion non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and other tumors with increased RET activity
Recent Clinical Research Accomplishments
OSUCCC – James Thyroid Cancer Research Bolstered by Two Prestigious Grants
Thyroid cancer research at the OSUCCC – James is making big strides, thanks to two large grants awarded by the National Cancer Institute (NCI) in 2013, including an $11.3 million, five-year Specialized Program of Research Excellence (SPORE) grant and an $11.3 million, five-year renewal of a Program Project Grant (PPG) that was first awarded in 2008.
The SPORE grant, which also involves scientists at MD Anderson Cancer Center in Houston, supports four interactive projects that collectively seek to: identify genetically at-risk individuals and allow for early diagnosis and prediction of tumor behavior; develop approaches to minimize treatment side effects; and develop better biomarkers and treatments for metastatic disease.
The PPG has four interactive research projects whose collective goals are to: better predict who is at risk, enable earlier diagnosis and predict tumor behavior by identifying predisposing genes; identify cell pathways that influence thyroid cancer development and progression for potential drug targeting; and determine why patients stop responding to standard therapy, then develop strategies that improve response rates. Matthew Ringel, MD, co-director of the Thyroid Cancer Unit at the OSUCCC – James, is principal investigator for both grants.
Researchers Find Candidate Gene for Susceptibility to Papillary Thyroid Cancer. A genomewide linkage analysis performed in 38 families helped a team of OSUCCC – James researchers identify SRGAP1as a candidate gene for susceptibility to papillary thyroid cancer (PTC), the most common form of thyroid cancer and one whose incidence is rising. Although PTC is mostly sporadic, about 5 percent of cases are familial. In a paper published in the Journal of Clinical Endocrinology and Metabolism, the researchers stated that, despite this high heritability, efforts to find predisposing genes have been largely negative. However, they noted that in a previous study involving linkage analysis of a large family with PTC and melanoma, they had identified a candidate noncoding RNA gene. That success prompted them to undertake this newer study, in which their findings point to the Slit-Robo Rho GTPase-activating protein 1 gene (SRGAP1) as a candidate susceptibility gene for PTC. Albert de la Chapelle, MD, PhD, was senior author on the paper.
Translational research accomplishments
BRAF Activates and Physically Interacts With PAK to Regulate Cell Motility. Researchers at the OSUCCC – James have identified a signaling pathway in thyroid cancer cells that is activated by the BRAF gene and interacts with the PAK gene to regulate cell motility. Writing in the journal Endocrine-Related Cancer, the investigators noted that increased p21-activated kinase (PAK) signaling had been previously identified in the invasive fronts of aggressive papillary thyroid cancers (PTCs). For this study, they hypothesized that BRAF, a central kinase in PTC formation and invasion, regulates thyroid cancer cell motility in part through PAK activation. The team used three well-characterized human thyroid cancer cell lines to explore their hypothesis and conclude that they had found a signaling pathway that could have clinical implications. Matthew Ringel, MD, was principal investigator.
Investigators Identify Mechanisms for Follicular Thyroid Cancer Development. Data from a study at the OSUCCC – James imply that that the protein kinase A and mammalian target of rapamycin (mTOR) signaling cascades are important biological mechanisms in the development of follicular thyroid cancer (FTC) and may serve as new targets for therapeutic intervention. The study, published in the Journal of Clinical Endocrinology and Metabolism, used mouse models and human tumor samples to characterize molecular mechanisms contributing to the development and metastasis of FTC, which has more frequent metastasis and a poorer prognosis than the more common papillary thyroid cancer. The researchers believe mouse models paralleling the development stages of human FTC should provide tools for further understanding the mechanics of this disease and for evaluating new therapeutics. Lawrence Kirschner, MD, PhD, was principal investigator.