Lung NETs and Their Treatment


Cancers that arise in the lung are mostly of the type known as NSCLC (non-small cell lung carcinoma). A much smaller proportion of lung tumors arise from neuroendocrine cells in the lungs. These cells (which are also found in most other organs) secrete a variety of hormones that are necessary for normal organ function, as well as for healing after injury or infection. Like other lung cells, neuroendocrine cells may transform to become cancers. Lung cancers that arise from neuroendocrine cells are called pulmonary neuroendocrine tumors (NETs), or lung NETs. Continue reading…


Hormone-Mimicking Drugs Are Used To Treat Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)


Neuroendocrine tumors (NETs) can arise wherever neuroendocrine (hormone-producing) cells are found—which is in most organs. Most NETs (65%-70%) are gastroenteropancreatic, or GEP, arising in different gastrointestinal organs. GEP-NETs are most commonly found in the small bowel (including the appendix), stomach, and rectum. Still, NETs in general are rare, which complicates the development of new treatments and identification of the genetic drivers of these cancers. Treatment of GEP-NETs is clearly an unmet medical need, and is now even more urgent because their incidence has been on the rise in the last 20 years. Continue reading…


Molecular Tumor Markers Could Reveal New Therapeutic Targets for Lung Cancer Treatment

The gist: New research looking into tumor mutations in small cell lung cancer (SCLC) and neuroendocrine tumors (NET) may open up new drug options to treat these conditions. Drugs called targeted therapies have been developed to treat people with tumors that have certain genetic mutations. Several targeted therapies are available for people with non-small cell lung cancer (NSCLC). But so far, targeted therapies have not been very useful in SCLC. Now, researchers have found that some SCLC and NET tumors may share some tumor mutations with NSCLC tumors. Theoretically, a patient with SCLC or NET could ask their oncologist for molecular testing to see whether their tumor(s) could potentially be treated off-label with an existing NSCLC drug. To learn more about SCLC treatment, see our Need to Know blog.

“Analysis of 607 small cell lung cancer (SCLC) lung tumors and neuroendocrine tumors (NET) identified common molecular markers among both groups that could reveal new therapeutic targets for patients with similar types of lung cancer, according to research presented today at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology. The Symposium is sponsored by the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), the International Association for the Study of Lung Cancer (IASLC) and The University of Chicago Medicine.

“This study examined the clinical specimens of 607 total cases of SCLC tumors (375) and lung NET (232), which included carcinoid, atypical carcinoid and large-cell neuroendocrine tumors. Biomarker testing was achieved through a combination of DNA sequencing (Next-Generation Sequencing (NGS) or Sanger-based); immunohistochemistry (IHC) to identify which proteins are present; and in situ hybridization (ISH) testing, a form of gene amplification, to determine if any of the markers that can cause cancer cells to grow or to become resistant to treatment are present…

” ‘Even cancers that appear to be very similar can be dramatically different at the molecular level, and these differences may reflect unique vulnerabilities that could positively impact therapeutic options and decisions,’ said Stephen V. Liu, MD, senior study author and Assistant Professor of Medicine in the Division of Hematology/Oncology at Georgetown University’s Lombardi Comprehensive Cancer Center in Washington, DC. ‘We are pleased that this research confirms these rarer subtypes; it calls for additional investigation on a larger scale. Once confirmed, molecular profiling of small cell tumors and NET could become standard, as it is currently for non-small cell lung cancers, which will be especially important as more molecularly targeted chemotherapy agents are developed.’ “


OncoBriefs: Local Tx for mRCC, Cervical Ca Prevention (CME/CE)

Editor’s note: This article describes three separate new findings in cancer research. The first is relevant for people with metastatic renal cell carcinoma (mRCC). Researchers have found that image-guided local ablation of tumors still has an important treatment role, even though there have been recent improvements in mRCC drugs. The second finding concerns people with metastatic neuroendocrine tumors (NETS). A clinical trial with volunteer patients found promising results for patients treated with the new drug lanreotide (aka Somatuline). The third finding has to do with preventing cervical cancer in women at high risk for the disease. The women involved in the study had high-grade cervical intraepithelial neoplasia (CIN 2/3), and were treated with surgical removal of the squamocolumnar junction (SCJ). These women had only low-grade recurrences, suggesting that removing SCJ cells might help prevent cervical cancer.

“More than 80% of patients with metastatic renal cell carcinoma (mRCC) remained alive without disease progression 3 years after image-guided local ablation of tumors, a retrospective study showed.

“Six of 76 evaluable tumors recurred an average of 1.6 years from treatment. Local ablation represents a “relatively safe procedure with acceptable local control rates,” authors concluded in an article published in the August issue of the Journal of Urology. A summary of the article leads off this edition of OncoBriefs, which also examines a somatostatin derivative for neurendocrine tumors and a surgical approach to cervical cancer prevention.”


Lanreotide Improves Survival with Enteropancreatic Tumors

The gist: A clinical trial with volunteer patients tested the effectiveness of a drug called lanreotide for people with grade 1 or 2 metastatic enteropancreatic neuroendocrine tumors. The researchers found that, compared to taking a “fake” placebo drug, lanreotide increased the amount of time patients lived without their disease worsening. However, lanreotide did not improve overall survival or quality of life.

“Lanreotide significantly improves survival among patients with metastatic enteropancreatic neuroendocrine tumors (grade 1 or 2), according to a study published in the July 17 issue of the New England Journal of Medicine.

“Martyn E. Caplin, D.M., from Royal Free Hospital in London, and colleagues conducted a multinational study of patients with advanced, well-differentiated or moderately-differentiated, nonfunctioning, somatostatin receptor-positive neuroendocrine tumors (grade 1 or 2 that originated in the pancreas, midgut, or hindgut, or were of unknown origin) and documented disease-progression status. Participants were randomly assigned to receive an extended-release aqueous-gel formulation of lanreotide at a dose of 120 mg (101 patients) or placebo (103 patients) once every 28 days for 96 weeks.

“The researchers found that, compared to placebo, lanreotide was associated with significantly prolonged progression-free survival (P placebo group. In predefined subgroups, the therapeutic effect was generally consistent with that found in the overall population. Groups were similar in quality of life and overall survival. Diarrhea was the most common treatment-related adverse event (26 percent of the lanreotide group versus 9 percent of the placebo group).”


A Drug Repositioning Approach Identifies Tricyclic Antidepressants as Inhibitors of Small Cell Lung Cancer and Other Neuroendocrine Tumors

Small cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with high mortality. We used a systematic drug repositioning bioinformatics approach querying a large compendium of gene expression profiles to identify candidate U.S. Food and Drug Administration (FDA)–approved drugs to treat SCLC. We found that tricyclic antidepressants and related molecules potently induce apoptosis in both chemonaïve and chemoresistant SCLC cells in culture, in mouse and human SCLC tumors transplanted into immunocompromised mice, and in endogenous tumors from a mouse model for human SCLC. The candidate drugs activate stress pathways and induce cell death in SCLC cells, at least in part by disrupting autocrine survival signals involving neurotransmitters and their G protein–coupled receptors. The candidate drugs inhibit the growth of other neuroendocrine tumors, including pancreatic neuroendocrine tumors and Merkel cell carcinoma.