MEN1-Related Neuroendocrine Tumors: A Patient's Guide to Promising New Treatments on the Horizon

Table of Contents

• Key Points
• What Are Multiple Endocrine Neoplasia (MEN) Syndromes?
• Understanding MEN1 (Wermer's Syndrome)
• Why Current Treatments Fall Short for MEN1 Patients
• How This Review Was Conducted
• The MEN1 Gene and Menin Protein: The Key to Understanding the Disease
• Emerging Therapy: Epigenetic Modulators
• Emerging Therapy: Wnt Pathway-Targeting Drugs
• Emerging Therapy: Ras/Raf/MEK/ERK Pathway Modulators
• Emerging Therapy: Akt/mTOR Pathway Modulators
• What These Findings Mean for Patients
• Study Limitations
• Recommendations for Patients
• Frequently Asked Questions
• Source Information

Key Points

• MEN1 causes multiple neuroendocrine tumors due to menin loss; current treatments are borrowed from sporadic tumor care.
• Promising preclinical therapies target epigenetic, Wnt, Ras, and mTOR pathways, but none are in human trials for MEN1 yet.
• Menin loss makes pancreatic cells more vulnerable to MAPK inhibition, suggesting a potential 'synthetic lethal' treatment strategy.
• Menin status may predict response to mTOR inhibitors like everolimus, moving toward personalized treatment for MEN1 tumors.
• Patients should seek specialized centers, consider NGS genetic testing, and participate in clinical trials when available.

What Are Multiple Endocrine Neoplasia (MEN) Syndromes?

The term "multiple endocrine neoplasia" (MEN) refers to a group of inherited disorders in which a person develops tumors in two or more hormone-producing (endocrine) glands. These are not common conditions, but they have a major impact on the people who carry the genetic mutations that cause them.

Based on specific gene mutations that lead to specific tumors in specific glands, medical researchers have identified four major subtypes of MEN, called types 1 through 4 (MEN1 to MEN4). The most frequently occurring of these is MEN1, which is the main focus of this review.

Here is a breakdown of the different MEN syndromes and the neuroendocrine tumors (NENs) associated with each:

• MEN1 (caused by mutations in the MEN1 tumor suppressor gene on chromosome 11): Associated with enteropancreatic tumors (affecting 30–70% of carriers), including gastrinomas (more than 40%), insulinomas (10–30%), glucagonomas (~3%), VIPomas (less than 1%), non-functioning pancreatic NENs (20–55%), and extremely rare somatostatinomas. It also causes "foregut" tumors (thymic, bronchial, and gastric NENs) in 2–10% of carriers, pituitary tumors in 30–40% (with prolactinomas being most common at 20%), and very rarely pheochromocytomas (less than 1%).
• MEN2 (MEN2A) (caused by mutations in the RET proto-oncogene on chromosome 10): Characterized by medullary thyroid carcinoma (MTC) in about 90% of carriers and pheochromocytomas in about 50%.
• MEN3 (MEN2B) (also caused by RET mutations): Features medullary thyroid carcinoma in more than 90% of carriers and pheochromocytomas in 40–50%, along with a marfanoid body type and ganglioneuromas (benign nerve tissue growths) of the lips, tongue, and colon. Unlike MEN2, it does not typically involve the parathyroid glands.
• MEN4 (caused by mutations in the CDKN1B tumor suppressor gene on chromosome 12): Commonly presents with parathyroid and pituitary tumors, with some cases involving pancreatic, duodenal, bronchial, and gastric NENs.

MEN2 and MEN3 sometimes cause tumors that overlap with those seen in MEN1, which can make diagnosis tricky. Because of this, doctors must carefully evaluate each patient's genetic profile and tumor pattern.

Understanding MEN1 (Wermer's Syndrome)

MEN1, also known as Wermer's syndrome, was first described in the early twentieth century, but it wasn't until 1954 that Dr. Wermer documented the first familial (inherited) case — a father and four of his nine children were all affected. Since that landmark observation, researchers have learned a great deal about this condition.

Patients with MEN1 characteristically develop tumors of the parathyroid glands with primary hyperparathyroidism (overactive parathyroid glands) in about 95% of patients, tumors of the anterior pituitary gland in about 30%, and tumors of the pancreatic islets (insulin-producing cells) in about 40%. Less commonly, patients may develop adrenal cortical adenomas or carcinomas, thyroid follicular adenomas, and neuroendocrine tumors outside the pancreas, such as duodenal gastrinomas or gastric, thymic, and bronchial carcinoids.

MEN1 is an autosomal dominant disorder, meaning that a child of an affected parent has a 50% chance of inheriting the mutated gene. The condition is caused by mutations in the MEN1 tumor suppressor gene, which provides the instructions for making a protein called menin (a 610-amino acid protein).

One important detail: in up to 10–30% of MEN1 patients, no mutation in the MEN1 gene can be found using standard testing methods. This is because routine approaches may miss mutations in non-coding and regulatory regions of the gene. Newer technology called next-generation sequencing (NGS) may help bypass these limitations, improving the accuracy of genetic diagnosis.

The outlook for MEN1 patients has changed dramatically over the past century. Before 1980, about 80% of MEN1-related deaths were caused by complications from gastrinoma-driven stomach acid hypersecretion — leading to multiple gastrointestinal ulcers, bleeding, and perforation. Better medications to control hypergastrinemia (excess gastrin in the blood) and stomach acid have significantly reduced deaths from these complications.

However, serious challenges remain. Most MEN1 patients with pancreatic or thymic NENs (about 70–90%) will need some form of treatment during their lifetime, including surgery and/or systemic therapy, due to tumor progression, recurrence, or the presence of multiple tumors at once. Despite advances in care, the life expectancy of MEN1 patients remains shorter than the general population, with a mean age at death of about 55 years. Death most often occurs as a result of malignant progression of pancreatic NENs (responsible for about 50% of fatalities) and thymic NENs (about 24% of fatalities).

Why Current Treatments Fall Short for MEN1 Patients

The standard treatment options for neuroendocrine tumors — including surgical removal, somatostatin analogues (SSAs), mTOR inhibitors, tyrosine kinase (TK) inhibitors, peptide receptor radioligand therapy (PRRT), chemotherapy, and liver-directed therapies — have never been formally evaluated in MEN1 patients specifically. Instead, these treatments have been developed for patients with sporadic (non-inherited) NENs and then extrapolated to the MEN1 population.

This creates a significant problem. MEN1-related NENs tend to behave differently than sporadic tumors. They are often:

• Multiple and multicentric — many tumors can develop simultaneously in different locations
• Heterogeneous — different tumors within the same patient can have different biological behaviors and malignant potential
• More resistant to conventional therapies — compared to their sporadic counterparts
• Associated with a poorer prognosis — partly due to this treatment resistance

The multi-focality (multiple tumors) and unpredictable malignant potential of MEN1-NENs make it difficult for surgeons to decide on the timing and extent of curative surgery. As a result, many patients need additional non-surgical treatments. Choosing the optimal therapy requires experienced, multidisciplinary teams at specialized referral centers of excellence.

How This Review Was Conducted

This is a review article, meaning the authors — a team of endocrinologists and researchers from Hadassah-Hebrew University Medical Center in Jerusalem, the University of Oxford in the UK, and the Structural Genomics Consortium — systematically gathered and analyzed all available published preclinical studies (research conducted in cells or animal models, before human trials) on emerging therapies for MEN1-related NENs.

The review focuses primarily on pancreatic NENs (pNENs), because these are the most frequently studied tumors in MEN1-NENs laboratory models to date. Since the medical community has recently shifted the terminology from "pituitary adenomas" to "pituitary neuroendocrine neoplasms," the authors also briefly describe relevant data on MEN1-pituitary tumors where available.

Since the discovery of the MEN1 gene in 1997, researchers have worked to understand how menin works at the molecular level. Laboratory models — including genetically engineered mice with MEN1 mutations that closely mimic the human disease — have been essential tools for testing new therapies before they can be considered for human trials.

The MEN1 Gene and Menin Protein: The Key to Understanding the Disease

Menin is a protein found throughout the body that acts as a nuclear scaffold protein — meaning it helps organize other proteins and molecular complexes within the cell nucleus. Fascinatingly, menin has opposing roles in different organs: it acts as a genuine tumor suppressor in endocrine organs, yet it is essential for promoting leukemia in mouse models. This dichotomy is the result of menin's ability to regulate gene expression in opposite directions depending on the cellular context.

Here is what menin does in the cell, in simplified terms:

In the nucleus (control center of the cell): Menin interacts with a protein called JunD and an enzyme called PRMT5 to suppress (turn off) the transcription of target genes. It also binds to chromatin-modifying protein complexes — including the mixed lineage leukemia proteins MLL1 and MLL2 and a protein called Smad3 (a TGF-β signaling component) — to promote (turn on) transcription of other target genes. Additionally, menin restricts the Wnt pathway by blocking β-catenin (a key signaling protein) from entering the nucleus, which prevents the activation of Wnt target genes.

In the cytoplasm (the cell body): Menin binds to a protein called Akt, inhibiting the mTOR pathway (a major cell-growth pathway) downstream of PI3K. It also hampers ERK-dependent K-Ras phosphorylation, preventing the interaction between SOS and K-Ras — which effectively blocks a key step in the Ras signaling cascade that drives cell proliferation.

When menin is lost or not functioning properly, these regulatory mechanisms fail, and cells begin to divide and grow unchecked. Understanding these specific pathways has allowed researchers to identify potential targeted therapies, each designed to counteract the effects of menin loss.

Emerging Therapy: Epigenetic Modulators

One of the most promising areas of research involves epigenetic modulators — drugs that affect how genes are turned on and off without changing the underlying DNA sequence. Menin plays a critical role in epigenetic regulation, including the modification of histones (the proteins that DNA wraps around in the nucleus). Specifically, menin interacts with histone methyltransferases like MLL1 and PRMT5, as well as acetyltransferase complexes (HDACs), to regulate the expression of tumor suppressor genes including CDKN1B and GAS1.

Several classes of epigenetic drugs have been tested in preclinical models of MEN1-NENs:

BET inhibitors. JQ1, a drug that inhibits the BET family of proteins (bromo and extra terminal domain proteins that bind to acetylated histones to promote gene transcription), has shown encouraging results. In laboratory studies, JQ1 decreased cell proliferation and increased apoptosis (programmed cell death) of pancreatic, pituitary, and bronchial NEN cell lines. It also reduced ACTH secretion from ACTH-secreting pituitary cell lines (AtT20 cells) — a finding with potential relevance for patients with Cushing's disease. In a mouse model using a pancreatic β-cell-specific conditional Men1-knockout (which develops pNENs), JQ1 was shown to decrease proliferation and increase apoptosis of the pancreatic tumors.

A second BET inhibitor, CPI203, has also been reported to reduce pNEN proliferation in a BON-1 xenograft model (human tumor cells implanted into mice).

HDAC inhibitors. The potential utility of histone deacetylase inhibitors (HDACi) has been demonstrated in some sporadic NENs, though specific studies in MEN1-NENs models are limited. However, the early results are notable:

• LMK-235 (an HDAC5 inhibitor) has been reported as a potential therapeutic target in pNENs.
• Etinostat (a Class I HDAC1/3 inhibitor) was able to inhibit "master regulator" proteins in 42% of cultured rodent islet tumor cells and reduced tumor growth in a small intestinal NEN xenograft mouse model.
• SAHA (suberoylanilide hydroxamic acid) was reported to decrease proliferation and increase apoptosis in a GH3 rat pituitary NEN cell line.
• Some HDAC inhibitors — including vorinostat (SAHA), romidepsin, and panobinostat — have already been approved by the U.S. Food and Drug Administration (FDA) for specific blood cancers (hematologic malignancies), though they have shown only limited efficacy in patients with sporadic pNENs.

Menin also forms a complex with MLL and Ash2 proteins to promote histone 3, lysine 4 (H3K4) methylation, which increases the expression of anti-proliferative genes, including cyclin-dependent kinase (CDK) inhibitors that encode the proteins p27 and p18. Preclinical studies have demonstrated that genetically removing Rbp2 (a H3K4 demethylase — an enzyme that removes methyl groups from histones) can reduce proliferation of pNEN cells and reduce pancreatic tumor burden in Men1 conditional knockout mice. Since Rbp2 expression has been reported to be elevated in NENs, targeting this enzyme could offer a novel therapeutic approach for MEN1-associated tumors.

Emerging Therapy: Wnt Pathway-Targeting Drugs

The Wnt/β-catenin signaling pathway is critical for cell growth and development, and it is often disrupted in cancer. Normally, menin reduces cell proliferation through this pathway by promoting β-catenin phosphorylation and its removal from the nucleus. When menin is absent, β-catenin accumulates in the nucleus and activates the transcription of genes that drive tumor growth.

Several studies have explored whether drugs that interfere with this pathway could help MEN1 patients:

In a study using both Men1-null mouse embryonic fibroblasts (MEFs) and insulinoma tissues from β-cell-specific Men1-knockout mice (which show nuclear accumulation of β-catenin), Cao and colleagues demonstrated that overexpressing menin reduces β-catenin nuclear accumulation and its transcriptional activity. They also showed that menin directly interacts with β-catenin and carries it out of the nucleus through a process called nuclear-cytoplasmic shuttling.

In another study using MEN1-deficient mice that develop pNENs (RIP-Cre mice with pancreatic β-cell conditional knockout of menin), Jiang and colleagues found that additionally knocking out β-catenin decreased the number and size of pancreatic tumors and increased mouse survival.

Furthermore, the use of a β-catenin antagonist called PKF115-584 decreased pNEN cell proliferation in laboratory studies.

These findings suggest that Wnt-signaling modulators may represent a completely new approach to treating MEN1-NENs patients. That said, the authors caution that the interactions between menin, Wnt, and β-catenin are complex — menin may promote or inhibit Wnt signaling at different stages of tumor development and in different cell types — and these interactions "remain yet to be explored."

Emerging Therapy: Ras/Raf/MEK/ERK Pathway Modulators

The RAS-RAF-MEK-ERK pathway (often called the MAPK pathway) is a chain of proteins that transmits signals from the cell surface to the nucleus, controlling cell division and survival. This pathway is aberrantly activated in many types of cancer, and NENs are no exception.

Initial studies have shown that NENs display activating mutations in the Ras family of signal-transducing genes, over-activity of p21(Ras) signaling pathways, or constitutive (continuous) activation of upstream or downstream effectors of Ras — including growth factor receptors, PI(3)-kinase, and Raf/mitogen-activated protein kinases.

Several key experiments have shed light on how menin interacts with this pathway:

Kim and colleagues demonstrated that overexpressing menin in pro-oncogenic RAS-transformed murine NIH3T3 cells (a type of laboratory cell line) decreased cell proliferation and tumor growth in athymic mice, effectively restraining the cancer-promoting effects of RAS.

Chamberlain and colleagues made a surprising discovery: K-Ras (a member of the Ras family) paradoxically suppressed growth in pancreatic endocrine cells in a mouse model. This effect depended on the antiproliferative Ras effector RASSF1A and on menin's blockade of the Raf/MAPK pathway. Interestingly, stimulating ERK1/2 phosphorylation while also using a menin inhibitor synergistically enhanced proliferation, whereas inhibiting MAPK signaling had a lethal effect when menin was absent.

Recently, using a genetically engineered mouse model with an ATII-specific Kras^G12D/+/Men1^−/− mutation, researchers showed that menin deficiency results in increased tumor formation, further confirming menin's role as a critical brake on the Ras signaling pathway in endocrine tissues.

These insights suggest potential strategies for targeting menin-sensitive endocrine tumors through the Ras/Raf/MEK/ERK axis.

Emerging Therapy: Akt/mTOR Pathway Modulators

The mTOR pathway is a central regulator of cell growth and metabolism, and it is already a target of approved cancer drugs. The mTORC1 inhibitor RAD001 (everolimus) is currently used in clinical practice for non-MEN1 NENs of various origins. However, data specifically on how menin interacts with the Akt/mTOR pathway in MEN1-related tumors have been limited — until recently.

Razmara and colleagues conducted a study to assess the impact of menin expression — alone or combined with rapamycin (another mTOR inhibitor) — on cell proliferation in a cell-line model using menin-silenced BON-1 cells (a human pancreatic carcinoid cell line). Their findings were striking:

• Lack of menin enhanced mTORC2-Akt activation
• Lack of menin increased rapamycin-induced pAkt (phosphorylated Akt)
• There was a direct negative regulation between menin and rapamycin-mediated mTORC2-Akt activation

These results suggest that menin is essential in mTORC1/C2 crosstalk and may influence how pNEN patients respond to mTOR inhibitor drugs. In simpler terms: knowing a patient's menin status could help doctors predict whether mTOR inhibitors will work for them.

Wang and colleagues provided additional evidence that menin is an important negative regulator of Akt kinase activity. Using a Men1^+/− mouse model bearing islet adenomas, they performed immunohistochemistry (IHC) staining for pAkt(S473) and menin on tumors from 18-month-old mice. Their findings showed that pAkt(S473) expression in islet adenomas correlates with loss of menin expression — meaning that when menin is gone, Akt becomes overactive. This demonstrates that menin downregulates AKT activity and inhibits both Akt-induced proliferation and Akt's anti-apoptosis (cell-survival) effects.

What These Findings Mean for Patients

This review brings together several important messages for patients living with MEN1 and their families:

First, there is hope on the horizon. The identification of multiple new therapeutic targets — epigenetic modulators, Wnt pathway inhibitors, Ras pathway modulators, and Akt/mTOR pathway drugs — means that researchers are actively working on treatments specifically designed for the unique biology of MEN1-related tumors. This is a significant step forward, since current treatments were developed for sporadic NENs and simply "borrowed" for MEN1 patients.

Second, personalized medicine may become a reality. The finding that menin status affects how pancreatic NEN cells respond to mTOR inhibitors (like everolimus) suggests that, in the future, genetic testing of tumors may guide treatment choices. Patients whose tumors have certain molecular characteristics might benefit from one type of therapy, while others would need a different approach.

Third, combination therapies may be the key. Several studies in this review suggest that combining epigenetic drugs with other anticancer agents — or using drugs that target multiple pathways simultaneously — could produce better results than single agents alone. For example, the finding that menin loss makes pancreatic cells more vulnerable to MAPK inhibition suggests a potential "synthetic lethal" strategy: if you can't replace the missing menin, target the pathways that become overactive in its absence.

Fourth, repurposing existing drugs offers a faster path forward. Some of the drugs discussed in this review — such as vorinostat, romidepsin, and panobinostat — are already FDA-approved for other conditions. If clinical trials confirm their effectiveness in MEN1-NENs, they could become available to patients more quickly than entirely new drugs.

Study Limitations

It is important to understand the limitations of the research presented in this review:

• Preclinical only: All of the studies discussed were conducted in laboratory cell lines or animal models (mostly mice). None of these therapies have been formally tested in randomized controlled clinical trials specifically for MEN1 patients.
• Limited MEN1-specific data: Most of the research performed to date on MEN1-NENs almost exclusively involves pancreatic tumors extracted from MEN1-mouse models. Fewer studies have addressed pituitary, thymic, or bronchial MEN1-associated tumors.
• Inconsistent tumor behavior: The authors note that individual tumor behavior in MEN1 mouse models "may be variable," meaning that results observed in one model may not reliably predict what happens in a different model — or in human patients.
• Unresolved biological questions: The menin/Wnt/β-catenin interactions remain incompletely understood, and menin may either promote or inhibit Wnt signaling depending on the stage of tumor development and the cell type involved. This complexity means that Wnt-targeting drugs might have unpredictable effects.
• Limited clinical efficacy data: Even for drugs already approved by the FDA for blood cancers (the HDAC inhibitors), limited efficacy has been demonstrated in patients with sporadic pNENs — underscoring the challenge of translating preclinical success to real-world patient benefit.

The authors also note that clinical data using standard therapeutic options in MEN1-related NENs are generally scarce, and the existing treatment options "have not been formally evaluated in MEN1 patients." This scarcity of evidence highlights the urgent need for dedicated clinical research in this population.

Recommendations for Patients

Based on the findings of this review, patients with MEN1 and their families may consider the following:

1. Seek care at a specialized center. The authors emphasize that managing MEN1-NENs requires "experienced multi-disciplinary teams inside referral centers of excellence." If possible, seek evaluation at a center with an ENETS (European Neuroendocrine Tumor Society) Center of Excellence or equivalent designation.
2. Stay informed about clinical trials. As these preclinical therapies advance toward human testing, clinical trials for MEN1 patients may become available. Discuss trial eligibility with your specialist team.
3. Consider genetic counseling and testing. Because up to 10–30% of MEN1 patients have negative standard genetic testing, ask about next-generation sequencing (NGS), which may detect mutations in non-coding regions that standard tests miss.
4. Understand that current treatments are extrapolated. Know that the standard therapies offered today were largely developed for sporadic NENs and have not been formally evaluated in MEN1 patients. This underscores the importance of shared decision-making with your doctors about the risks and benefits of each option.
5. Monitor proactively. Because MEN1 patients often develop multiple tumors over their lifetime — and up to 70–90% will need therapeutic intervention — regular surveillance with imaging and hormone level testing is critically important.

Frequently Asked Questions

What is MEN1 and how is it inherited?

MEN1 is a rare inherited condition that causes tumors in two or more hormone-producing glands. It is caused by mutations in the MEN1 tumor suppressor gene. A child of an affected parent has a 50% chance of inheriting the mutated gene. Most patients develop overactive parathyroid glands, and many develop pituitary or pancreatic tumors.

Why do current treatments for MEN1 tumors fall short?

Current treatments for neuroendocrine tumors, such as surgery, somatostatin analogues, and chemotherapy, were developed for sporadic tumors, not MEN1. MEN1 tumors are often multiple, multicentric, and more resistant to conventional therapy. They also carry a poorer prognosis. Because treatments have not been formally evaluated in MEN1 patients, doctors must extrapolate results from sporadic tumor studies.

What promising new treatments are being researched for MEN1?

Researchers are studying several targeted therapies in laboratory and animal models. These include epigenetic modulators like BET inhibitors and HDAC inhibitors, drugs that block the Wnt pathway, Ras/Raf/MEK/ERK pathway modulators, and Akt/mTOR pathway inhibitors. These treatments aim to counteract the effects of menin loss. None have reached human trials specifically for MEN1 yet.

What is menin and why is it important in MEN1?

Menin is a protein that acts as a tumor suppressor in endocrine organs. It regulates gene expression, restricts the Wnt pathway, and inhibits the mTOR and Ras signaling pathways. When menin is lost or not working, cells grow unchecked. Understanding menin's role has helped researchers identify potential targeted therapies for MEN1-related tumors.

Should I consider genetic testing for MEN1 with next-generation sequencing?

The article suggests asking about next-generation sequencing, or NGS. Standard genetic tests may miss up to 10–30% of MEN1 mutations because they can be in non-coding regions. NGS may detect these mutations and improve diagnostic accuracy. Genetic counseling can help you understand the benefits and implications of testing.

What should I do as a MEN1 patient based on this review?

The authors recommend seeking care at a specialized center with a multidisciplinary team. Stay informed about clinical trials for new therapies. Ask about genetic counseling and NGS testing. Understand that current treatments were developed for sporadic tumors and may not be fully effective. Regular surveillance with imaging and hormone tests is critical because many patients develop multiple tumors over time.

When should a patient with MEN1-related neuroendocrine tumors get a second opinion?

Patients with MEN1-related neuroendocrine tumors should consider a second opinion before starting treatment, because current therapies were developed for sporadic neuroendocrine tumors and have not been formally evaluated in MEN1 patients. In MEN1, 70–90% of patients will need treatment, and managing these tumors requires multidisciplinary teams at specialized referral centers. A second opinion can help confirm the diagnosis, review whether the recommended surgery or systemic therapy is necessary, and identify whether clinical trials of emerging targeted therapies are available. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: Preclinical drug studies in MEN1-related neuroendocrine neoplasms (MEN1-NENs)

Authors: Simona Grozinsky-Glasberg, Kate E Lines, Shani Avniel-Polak, Chas Bountra, and Rajesh V Thakker

Author affiliations: Neuroendocrine Tumor Unit, ENETS Center of Excellence, Department of Endocrinology and Metabolism, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, Oxford, UK; Structural Genomics Consortium, University of Oxford, Oxford, UK

Journal: Endocrine-Related Cancer (2020), Volume 27, pages R345–R355

DOI: https://doi.org/10.1530/ERC-20-0127

Publisher: Society for Endocrinology, published by Bioscientifica Ltd.

Note: This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and does not constitute medical advice. Patients should always consult their healthcare team about their individual treatment options.