Related Experiment Video

Updated: Jun 12, 2025

Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
09:33

Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens

Published on: August 25, 2023

1.1K

Molecular Genetics of Pheochromocytoma/Paraganglioma

Heather Wachtel1, Katherine L Nathanson2

  • 1Hospital of the University of Pennsylvania, Department of Surgery, Division of Endocrine and Oncologic Surgery and the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Current Opinion in Endocrine and Metabolic Research
|September 27, 2024
PubMed

Insights

Pheochromocytomas and paragangliomas (PPGL) are rare tumors. This review explores their genomic subtypes, tumor microenvironment, and emerging molecular targets for new diagnostic and therapeutic strategies.

Area of Science:

  • Endocrinology
  • Oncology
  • Genetics

Background:

  • Pheochromocytomas and paragangliomas (PPGL) are neuroendocrine tumors causing cardiovascular issues due to catecholamine secretion.
  • Current treatments for metastatic PPGL are limited, with no targeted therapies available.
  • Germline variants are linked to 25% of PPGL cases, increasing risk for multifocal and metastatic disease.

Purpose of the Study:

  • To review recent research on the tumor microenvironment in PPGL.
  • To summarize the genomic drivers of PPGL tumorigenesis and progression.
  • To highlight current research on molecular targets for novel diagnostic and therapeutic strategies in PPGL.

Main Methods:

  • Review of recent studies on PPGL tumor microenvironment.
  • Analysis of genomic drivers in PPGL tumorigenesis.
  • Exploration of current research on molecular targets for PPGL.

Main Results:

  • PPGL classified into three genomic subtypes: Cluster 1 (pseudohypoxia), Cluster 2 (kinase signaling), and Cluster 3 (Wnt-altered).
  • Understanding of somatic driver mutations is continually evolving.
  • Research is identifying potential molecular targets for diagnosis and therapy.

Conclusions:

  • Advances in understanding PPGL genomics and tumor microenvironment are crucial.
  • Novel molecular targets offer promise for improved diagnostic and therapeutic strategies.
  • Targeted therapies are needed for metastatic pheochromocytomas and paragangliomas.
Keywords:
Pheochromocytomagenomicsgermline pathogenic variantneuroendocrine tumorparagangliomasomatic mutation

More Related Videos

Author Spotlight: Genetically Engineered Mouse Models and Pathological Characterization of Neurofibromatosis Type 1 Associated Tumors08:57

Author Spotlight: Genetically Engineered Mouse Models and Pathological Characterization of Neurofibromatosis Type 1 Associated Tumors

Published on: May 17, 2024

1.9K
Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

1.7K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Human Genetics01:28

Human Genetics

Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
542
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.3K
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.7K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
2.4K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.3K