Home » Targeted Therapies in Neuroendocrine Tumour Treatment
Neuroendocrine tumours (NETs) require specialised treatment approaches due to their complex biology and varying behaviour.
Targeted therapies have emerged as a cornerstone of NET management, offering precision treatment that interferes with specific molecular pathways critical to tumour growth.
This article explores the mechanisms, benefits, and challenges of targeted therapies in NET care, highlighting current treatments and future directions.
Neuroendocrine Cancer Australia (NECA), is dedicated to supporting individuals diagnosed with NETs, and their families. NECA offers a wealth of resources, educational programs, and advocacy efforts aimed at deepening the understanding of NETs, improving patient care, and encouraging research advancements. Patients diagnosed with NETs can engage with NECA’s comprehensive support and information by calling the NET nurse line.
Targeted therapies are specialised treatments designed to interfere with specific molecules or pathways involved in cancer growth and progression. Unlike traditional therapies, which affect both cancerous and healthy cells, targeted therapies selectively attack tumour cells by blocking signals essential for their survival and proliferation. This precision reduces damage to healthy tissues and improves treatment outcomes.
Traditional treatments like chemotherapy and radiation target rapidly dividing cells indiscriminately, often leading to significant side effects. In contrast, targeted therapies focus on molecular drivers of cancer, offering a more refined approach. They are tailored to the biological characteristics of the tumour, making them particularly effective in NETs, where molecular pathways like somatostatin receptor signalling and angiogenesis play critical roles.
Understanding the molecular pathways involved in neuroendocrine tumour growth has led to the development of therapies that specifically target these processes.
Somatostatin receptors are a hallmark of many NETs, particularly those originating in the gastrointestinal tract and pancreas. These receptors regulate hormone secretion and tumour growth. Targeting somatostatin receptors with somatostatin analogues (SSAs) has proven effective in controlling symptoms and slowing disease progression.
Vascular endothelial growth factor (VEGF) promotes the formation of new blood vessels, a process known as angiogenesis, which is essential for tumour growth and metastasis. By targeting VEGF and its pathways, therapies can inhibit the tumour’s ability to develop its blood supply, effectively starving it of nutrients and oxygen.
The mammalian target of rapamycin (mTOR) pathway regulates cell growth, proliferation, and survival. Aberrant activation of this pathway is common in NETs, contributing to tumour progression. Targeting mTOR with inhibitors like everolimus disrupts these signals, offering a valuable therapeutic option for NET patients.
Several targeted therapies are now available for NETs, each addressing different molecular pathways critical to the development and progression of these tumours.
Octreotide and lanreotide are synthetic versions of somatostatin, a hormone that naturally inhibits the secretion of other hormones. These drugs bind to somatostatin receptors on NET cells, reducing hormone-related symptoms like flushing and diarrhoea.
They also have antiproliferative effects, slowing tumour growth and extending progression-free survival in patients with functional and non-functional NETs.
Everolimus, an oral mTOR inhibitor medication, blocks the mTOR pathway to reduce tumour growth and proliferation. It is approved for advanced pancreatic NETs, as well as some gastrointestinal and lung NETs.
Clinical trials have shown that everolimus significantly improves progression-free survival. However, it can cause side effects like fatigue, mouth sores, and immunosuppression, which require careful management.
Sunitinib, a TKI targeting VEGF receptors, is specifically approved for pancreatic NETs. By inhibiting angiogenesis, it reduces the blood supply to tumours, slowing their growth.
Sunitinib has shown efficacy in improving progression-free survival, but side effects such as hypertension, diarrhoea, and hand-foot syndrome may occur.
PRRT uses a somatostatin analogue linked to a radioactive isotope, such as lutetium-177. This therapy delivers targeted radiation directly to NET cells expressing somatostatin receptors, minimising damage to healthy tissues. PRRT has shown remarkable success in treating advanced NETs, improving both progression-free survival and quality of life.
The decision to use targeted therapies in NETs depends on various factors, including tumour type, grade, and the extent of the disease.
The choice of targeted therapy depends on the tumour’s grade, type, and molecular profile. SSAs are commonly used for low- to intermediate-grade NETs, while mTOR inhibitors and TKIs are often reserved for advanced or progressive disease. PRRT is typically considered for metastatic or inoperable NETs with high somatostatin receptor expression.
SSAs are often the first-line treatment for functional and non-functional NETs, controlling symptoms and slowing tumour growth. For patients with disease progression or resistance to first-line therapies, second-line options like everolimus, sunitinib, or PRRT are considered.
Targeted therapies are particularly valuable in metastatic and advanced NETs, where traditional treatments may be less effective. They offer a tailored approach that addresses the unique biology of the tumour, improving outcomes even in challenging cases.
Targeted therapies offer significant benefits over traditional treatments, improving survival outcomes while maintaining a better quality of life for patients.
Targeted therapies have significantly extended progression-free survival in NET patients. By controlling tumour growth and alleviating hormone-related symptoms, these treatments improve patients’ quality of life, allowing them to manage their condition effectively over time.
Compared to traditional chemotherapy, targeted therapies typically have a better safety profile. Their ability to selectively target tumour cells reduces systemic side effects, making them more tolerable for long-term use.
Despite their effectiveness, targeted therapies come with challenges such as drug resistance, side effects, and accessibility, which must be addressed to optimise their use.
One of the main challenges with targeted therapies is the development of drug resistance. Tumours can adapt to therapy over time, leading to reduced efficacy. Combination strategies and the development of next-generation targeted agents are being explored to address this issue.
While targeted therapies have lower toxicity than chemotherapy, they are not without side effects. Common issues include fatigue, diarrhoea, and skin reactions. Effective side effect management is essential to ensure patients can continue treatment without compromising quality of life.
The high cost of targeted therapies can be a barrier for many patients. Ensuring equitable access to these treatments is a priority for healthcare systems worldwide, particularly in low-resource settings.
Combining targeted therapies with other treatment modalities has the potential to enhance efficacy and overcome limitations like resistance.
Somatostatin analogues and PRRT has shown effects in slowing tumour growth and managing symptoms. This approach leverages the strengths of both therapies to maximise patient outcomes.
Targeted therapies are increasingly being combined with chemotherapy and immunotherapy to overcome resistance and enhance efficacy. These combination strategies are the focus of ongoing clinical trials, offering hope for improved survival and better disease control.
Research is underway to develop new targeted therapies that address the limitations of current treatments. Novel agents targeting alternative pathways, such as HIF-1α and PI3K, are showing promise in preclinical and early clinical studies.
Biomarkers play a critical role in identifying patients who are most likely to benefit from targeted therapies. Advances in biomarker research, such as somatostatin receptor density and genetic profiling, are paving the way for personalised treatment approaches.
Expanding access to clinical trials is essential for advancing targeted therapies in NETs. Global collaborations and investments in research infrastructure are crucial for ensuring that patients worldwide can benefit from these innovations.
Targeted therapies have revolutionised the treatment landscape for neuroendocrine tumours, offering precision, improved survival, and better quality of life for patients.
While challenges like resistance and accessibility remain, ongoing research and innovations hold the promise of even more effective and personalised options in the future.
Patients are encouraged to consult with their healthcare team or reach out to Neuroendocrine Cancer Australia for guidance and support in exploring targeted therapies for NETs.
Further information and support for people diagnosed with NETs is available by calling the NECA NET nurse line.