Systemic Consequences of Pulmonary Hypertension and Right-Sided Heart Failure | Circulation
Risks And Causes Of Neuroendocrine Cancer
We don't know what causes most neuroendocrine cancers. But there are some risks factors that can increase your risk of developing it. These include an inherited condition called MEN 1. Anything that can increase your risk of getting a disease is called a risk factor. Different cancers have different risk factors. Having one or more of these risk factors doesn't mean you will definitely get that cancer. There are 2 key groups of neuroendocrine cancer: Neuroendocrine cancer starts in different parts of your body. Where it starts is called the primary site. The possible risks and causes of NETs and NECs are different. And the risks also depend on your primary site. Inherited conditions Most neuroendocrine cancers are not inherited
. Doctors call these sporadic cancers. This means they don't know why you have developed the cancer. There isn't a known genetic (inherited) link. But there are some rare inherited conditions that can run in families. These can increase your risk of developing some types of NET. Multiple endocrine neoplasia 1 (MEN1) MEN1 is a rare inherited condition. It can cause tumours to develop in different parts of the body. For example, the pancreas, parathyroid gland and pituitary gland. The tumours can be benign or cancerous. People with MEN1 have a higher risk of developing NETs in the pancreas. The risk increases as you get older. Research has shown that by the age of 80, up to 80 out of 100 people with MEN 1 (up to 80%) get a NET in the pancreas or duodenum. Sometimes people with MEN 1 develop lung or stomach NETs. But this is less common than developing pancreatic NETs. Neurofibromatosis type 1 Neurofibromatosis type 1 (NF1) is caused by a change in the NF1 gene. The faulty gene is usually passed on from parents to their children. NF1 can increase your risk of developing some cancer types. This includes neuroendocrine tumours (NETs). Von Hippel-Lindau (VHL) VHL is a rare inherited condition caused by a change in the von Hippel-Lindau gene. It can affect different parts of the body. People with VHL have an increased risk of developing different types of tumours. These include pancreatic NETs. Tuberous sclerosis (TSC) This is a rare inherited condition. It causes tumours to develop in different parts of the body. Most tumours are benign. Researchers think that people with tuberous sclerosis may have a higher risk of developing a pancreatic NET But this is rare. Other risk factors Other risk factors include: Age You can get neuroendocrine cancer at any age. It is most common in people aged 55 and older. Smoking Smoking is the biggest preventable cause of cancer. Smoking increases your risk of developing lung neuroendocrine carcinoma (NEC). Even light or occasional smoking increases the risk of cancer. But your risk increases more the longer you smoke and the more you smoke. If you are a smoker, the best thing you can do for your health is quit. Drinking alcohol There are mixed results from the research looking at alcohol and neuroendocrine cancer risk. Some studies have shown that drinking heavily may increase the risk of pancreatic NETS. The UK government guidelines advise both men and women to drink no more than 14 units of alcohol a week. Diabetes Diabetes is a disease that causes the blood sugar level to increase. There is some evidence that people with diabetes have an increased risk of developing a pancreatic NET. Diabetes is a common disease. Most people with diabetes will not develop a NET of the pancreas. Family history of cancer Researchers have found that your risk of developing some types of neuroendocrine cancer might be higher if you have a close relative who has had cancer. A close relative is a parent or sibling. Long term stomach inflammation Some stomach NETs are linked to a condition called atrophic gastritis. This is a long term condition that causes inflammation of the stomach. Research has shown that there is a link between atrophic gastritis and type 1 stomach NET. Are there other causes? Stories about possible cancer causes are often in the media and it can be hard to know what's true and what's not. You may have heard of something that isn't included here. This is because we only include a risk factor in this information if it is supported by good quality evidence. Evaluating Radioligand Therapy Versus Everolimus In Lung NETs
Photo Credit: SciePro
The following is a summary of "A Randomized clinical trial evaluating the impact on survival and quality of life of 177Lutetium[Lu]-edotreotide versus everolimus in patients with neuroendocrine tumors of the lung and thymus: the LEVEL study (GETNE T-2217)," published in the April 2025 issue of BMC Cancer by Capdevila et al.
Neuroendocrine tumors (NETs) of the lung and thymus represent a rare and heterogeneous group of malignancies, often associated with limited therapeutic options once advanced disease develops. Everolimus currently remains the only approved systemic therapy for patients with advanced pulmonary or thymic NETs, highlighting a critical unmet need for novel, more effective treatments. A promising avenue involves targeting somatostatin receptor 2 (SSTR2), which is commonly overexpressed in lung-NETs and can be visualized through functional imaging modalities. This receptor profile offers a unique opportunity to employ radioligand therapies (RLT), such as 177Lu-edotreotide, in appropriately selected patients. Retrospective studies have suggested favorable outcomes using SSTR2-directed RLT in patients with lung-NET, prompting the design of the LEVEL trial to rigorously assess this approach in a prospective setting. The LEVEL study is a randomized, open-label, international Phase III clinical trial comparing the efficacy and safety of 177Lu-edotreotide versus oral everolimus in patients with well or moderately differentiated, progressive, locally advanced, or metastatic lung (typical or atypical) or thymic NETs.
Eligible participants—confirmed to have SSTR2 positivity through somatostatin receptor imaging—are randomized in a 3:2 ratio to receive either 6 cycles of 177Lu-edotreotide (administered at 7.5 ± 0.7 GBq per cycle) or daily everolimus (10 mg), continued until disease progression or unacceptable toxicity occurs. The trial permits inclusion of treatment-naïve patients or those with prior progression on somatostatin analogues and up to two prior systemic therapies, excluding previous exposure to RLT or mTOR inhibitors. Imaging evaluations using CT or MRI are performed at 12-week intervals, and blood samples are collected at baseline, during the first tumor assessment, and at progression to evaluate pharmacodynamic biomarkers.
Additionally, archival tumor tissue will be used for ancillary exploratory analyses. The primary outcome measure is progression-free survival (PFS) as per RECIST v1.1, assessed by local investigators. Key secondary endpoints include overall survival, objective response rate, safety profile, and patient-reported quality of life using the EORTC QLQ-C30 instrument. The study aims to enroll 120 patients, with a statistical design powered to detect a 46.4% reduction in risk of disease progression (HR = 0.536) using a two-sided alpha of 5% and 80% power. An interim PFS analysis is planned based on the Lan-DeMets spending function with O'Brien-Fleming-like boundaries. Through its rigorous design and targeted approach, the LEVEL trial aims to establish whether 177Lu-edotreotide can serve as a new standard-of-care treatment for patients with advanced lung and thymic NETs, potentially expanding therapeutic options in this challenging disease setting.
Source:bmccancer.Biomedcentral.Com/articles/10.1186/s12885-025-13941-3
First Patient Dosed In A Phase 1/2 Trial For Small Cell Lung Cancer
The first patient with small cell lung cancer has been dosed in a phase 1/2 trial investigating first-line iadademstat plus immune checkpoint inhibitors.
First patient dosed in trial of iadademstat plus immunotherapy for small cell lung cancer.
The first patient with small cell lung cancer (SCLC) who has extensive disease has been dosed in a phase 1/2 trial of first-line iadademstat (ORY-1001), a potent and selective LSD1 inhibitor, in combination with immune checkpoint inhibitors, according to a news release from Oryzon Genomics.
The company also added that this is the first clinical trial testing the combination of iadademstat with immune checkpoint inhibitors.
"We are very excited to have the first patient dosed in this study. The biology underlying iadademstat's ability to make SCLC cells visible to the immune system and to boost significantly the number and the activation of cytotoxic CD8+ T cells is fascinating," Oryzon's CEO, Dr. Carlos Buesa, stated in the news release.
"Moreover, prior analyses of several phase 3 trials in SCLC indicate that low LSD1 expression is a key factor in determining patients' likelihood of responding and surviving. If this trial confirms the preliminary findings reported by researchers at MSKCC and others, it would reinforce the rationale for this combination as a therapeutic option for this critically underserved patient population. In the event of positive results, the company could also initiate a complementary trial to generate additional data in support of a potential accelerated registration strategy," he continued.
This investigation is entitled, "A Phase I Dose Finding and Phase II Randomized Trial of Iadademstat Combined With Immune Checkpoint Inhibition Maintenance After Initial Chemoimmunotherapy in Patients With Extensive-Stage Small Cell Lung Cancer", according to the news release. Investigators will evaluate the safety, tolerability, dose finding and efficacy of iadademstat in combination with an immune checkpoint inhibitor consisting of either Tecentriq (atezolizumab) or Imfinzi (durvalumab) in patients with extensive-stage small cell lung cancer who have initially received standard of care chemotherapy and immunotherapy.
Notably, according to the American Cancer Society, immune checkpoint inhibitors are a type of cancer treatment that helps the body's immune system find and attack cancer cells more effectively. These medicines do not kill cancer directly but instead work by blocking certain proteins that cancer uses to hide from the immune system. They are given intravenously or, in some cases, as an injection under the skin.
This early-phase clinical trial is a phase 1/2 study that is led and sponsored by the National Cancer Institute, with Dr. Charles Rudin from Memorial Sloan Kettering Cancer Center serving as the lead investigator. The study will take place at several well-known cancer centers across the United States, including Memorial Sloan Kettering and the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. The trial aims to enroll approximately 45 to 50 patients and is being conducted through a research partnership between Oryzon and the National Cancer Institute.
According to the news release, iadademstat is a small oral drug that blocks a specific enzyme which plays a role in how cancer cells grow and develop. It is being studied for its potential to treat both blood cancers and certain solid tumors. Early clinical trials in patients with relapsed or refractory acute myeloid leukemia have shown that the drug is well-tolerated and has strong clinical activity. Similar results were also seen when iadademstat was used in combination for newly diagnosed, older patients with the disease.
Moreover, ongoing studies are exploring its use with other treatments, and these studies are supported through partnerships with institutions like the National Cancer Institute and Oregon Health & Science University. Beyond blood cancers, iadademstat is being tested in solid tumors such as small cell lung cancer and neuroendocrine tumors, where it has shown initial signs of activity and safety. Additional trials are underway.
Iadademstat has also received orphan drug designation for acute myeloid leukemia in both the United States and Europe, and for small cell lung cancer in the United States, the news release concluded.
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