Precision Medicine Approaches for Neuroendocrine Tumors (NETs) - Overview

Introduction

Precision medicine is gaining popularity as a novel approach to studying neuroendocrine illnesses. The goal is to comprehensively understand the condition by investigating epigenetics and omics, ultimately leading to better patient management. Neuroendocrine neoplasms (NEN) are a broad group of malignancies that are becoming increasingly frequent. They share certain pathological characteristics but have distinct clinical presentations and outcomes. Immunotherapies and metabolic profiling are two novel therapy options that have emerged since somatostatin analogs became available. Risk and predictive factors, as well as quality of life, are being thoroughly investigated.

What Is Neuroendocrine Tumor?

A neuroendocrine tumor is a type of cancer that grows in cells that make hormones and release them into the bloodstream in reaction to signals from the nervous system.

• Most neuroendocrine tumors start in the lungs, pancreas, or digestive system. When neuroendocrine tumors get bigger, they often spread to other organs like the liver. Neuroendocrine tumors can make hormones like serotonin, which can cause signs like diarrhea or a red face.

• Neuroendocrine tumors in the pancreas can sometimes be passed down through families and be linked to conditions like Multiple Endocrine Neoplasia type 1 (MEN1). Most neuroendocrine tumors, on the other hand, do not have known genetic or environmental reasons.

• Some neuroendocrine tumors can grow very quickly, while others grow more slowly. Differentiating tumors and grades can help describe how violent someone is. Tumors with a high score tend to grow quickly. Neuroendocrine carcinomas that have not differentiated properly are biologically different from neuroendocrine tumors that have differentiated properly. These are also cancers that grow very quickly.

• A lot of the time, neuroendocrine tumors are found because of symptoms caused by the growth of the cancer or the production of hormones. Neuroendocrine tumors are sometimes found by accident. Small, surface, low-grade neuroendocrine tumors may not do much harm depending on the cancer is location. For instance, neuroendocrine tumors that are small and well-differentiated in the stomach or rectum rarely spread. Atrophic gastritis is a disease that can lead to neuroendocrine tumors in the stomach. These tumors also behave in a harmless way.

What Is Precision Medicine?

Precision medicine tailors cancer treatment to a patient's unique genetic profile. Precision medicine examines cancer at a molecular level, unlike traditional techniques that focus on the organ of origin.

• Genomics is a key element of precision medicine, as researchers can identify the genetic factors that induce cancer, sometimes known as the "Achilles heel" of the tumor.

• After identifying the genetic cause of a tumor, we utilize this information to select treatments that target and eliminate specific genetic abnormalities and mutations in a patient's tumor while preserving healthy cells. Genomic sequencing can identify the genetic characteristics of a patient's cancer, potentially indicating that non-traditional drugs could be beneficial in treating the illness.

What Are the Cellular Changes in the NET?

The effects on cells that result from the genetic and epigenetic alterations seen in NETs are both the activation of proliferation and the loss of control over the cell cycle with the absence of apoptosis. Metastases and invasiveness have increased—alterations in metabolic processes (Kreb's cycle), hypoxia, and hypoxia with a pseudonym. The activation of epigenetic oncogenes is associated with the loss of anti-oncogene control and chromatin modification. The epigenetic, proteomic, and genetic regulation of NET cells is lost, which results in the development of fresh frameworks for clinical therapies.

What Are the Different Diagnostic Methods?

A medical professional typically performs diagnostic tests when a neuroendocrine tumor is suspected. These tests may include:

• An examination of the patient's medical history and an assessment of the body's state

• Laboratory examinations like blood and urine analyses.

• By injecting a radioactive tracer intravenously, medical imaging procedures like X-rays, ultrasounds, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) can be performed.

• A biopsy is a medical procedure in which a pathologist collects and examines a tiny sample of potentially abnormal cells to check for signs of cancer. Molecular studies that look at many factors, such as inherited risk factors, and the latest imaging methods can help doctors diagnose these conditions more accurately, give better prognostic information, and find new drug targets for treatment.

Neuroendocrine neoplasms are a rare type of cancer that comes from the neuroendocrine system, which is very spread out. As with cancer rehabilitation, a multidisciplinary method is needed to make the treatment more specific to each person.

What Are the Various Treatment Methods for Precision Medicine for Net?

Many hormones and markers of neuroendocrine growth are made by neuroendocrine neoplasms, which are made up of tumors. A lot of the time, people with NENs are only found after metastases have spread, even though surgery is still the most common way to treat localized tumors. Chronic medical care for these people needs to come from many different fields. Importantly, the grade and stage of the tumor, where it started in the body, and the presence of a functional syndrome are the main factors that today have a big impact on the treatment plan. On the other hand, the biological diversity of these neoplasms makes them less active in the clinic and less responsive to current treatments.

• Targeted Therapy: Targeted therapy is a fundamental aspect of precision cancer medicine. It involves using drugs targeting the genes and proteins in neuroendocrine tumors. These genes and proteins are crucial in cancer cell growth, division, and spread. Targeted medicines can eradicate cancer cells while minimizing harm to healthy cells by selectively interfering with certain biological targets.

• Immunotherapy: Innovative antigen changes in the microenvironment also occur. Various preclinical models have been used to study resistance to VEGF/VEGFR and mTOR inhibitors; nevertheless, there have been very few clinical applications of these inhibitors thus far. According to the preclinical evidence, odd patterns include the following: The mechanisms that lead to loss of sensitivity to targeted therapy could be at least partially reversible, in contrast to the mechanisms that lead to resistance to chemotherapy. Resistance to VEGFR inhibitors does not affect sensitivity to mTOR inhibitors. This presents the possibility of using sequential therapy with VEGFR and mTOR inhibitors as well as resistance to inhibitors of VEGFR and mTOR.

• Pharmaceutical Treatment: Administering potent anti-cancer drugs by intravenous or oral routes. These medications enter the bloodstream and disseminate throughout the body to specifically target and eliminate cancer cells that have spread. Short nuclear fragments, which make up DNA, are released into the bloodstream by tumor cells that are apoptotic or dying. It has been observed that levels increase with tumor growth and decrease after treatment. Monitoring levels may aid in pharmaceutical treatment and provide a more comprehensive picture of the mutational landscape of the NEN, as several anecdotal cases have recently demonstrated. Subclonal evolution may also cause changes in allele frequencies over time, meaning the treatment can be modified to combat emerging resistance.

• Somatostatin Analogs: Somatostatin analogs are synthetic compounds that mimic the effects of the natural hormone somatostatin. They are used to decrease the production of hormones by neuroendocrine tumors and hinder their growth.

• Peptide Receptor Radionuclide Therapy: Peptide receptor radionuclide therapy (PRRT) is a treatment method where a medicine specifically targeting cancer cells is combined with a small dose of radioactive material. This combination is administered intravenously, allowing the radiation to be directly delivered to the tumor.

• Radiation Therapy: Radiation therapy involves using a linear accelerator to produce powerful beams of high-energy particles, such as X-rays and protons, capable of eliminating cancer cells. The linear accelerator, positioned externally to the patient's body, can be precisely set to focus strong beams of radiation straight onto a tumor.

Conclusion

Precision medicine has come a long way in NET recently, and it now includes rare factors like MCC and MTC. The different inputs in this research topic show how the neuroendocrine field is changing as more patient-specific treatment methods are developed. This will likely lead to better patient care and a higher chance of life because of personalized treatments.