PAX2 shield vs PAX8 sword in ovarian cancer

Unlocking Ovarian Cancer: Can PAX Proteins Pave the Way for Targeted Therapies?

Avery Sinclair in Health & Wellness August 2025 • 4 min read.

"Delving into the divergent roles of PAX2 and PAX8 proteins in high-grade serous ovarian cancer could revolutionize treatment strategies and improve patient outcomes."

Ovarian cancer remains a significant threat to women's health, with high-grade serous ovarian cancer (HGSC) being the deadliest form. While traditionally believed to originate in the ovaries, mounting evidence points to the fallopian tubes as the primary source in many cases. This understanding has led researchers to investigate the roles of specific proteins, like PAX2 and PAX8, which are vital during the development of the fallopian tube.

PAX (paired box) genes, particularly PAX2 and PAX8, are transcription factors that regulate gene expression. Interestingly, PAX2 is often lost early in the progression of serous cancer, while PAX8 is commonly present. These proteins influence key cancer processes like migration, invasion, and cell survival, making them potential targets for new treatments.

This article explores the contrasting roles of PAX2 and PAX8 in ovarian cancer, investigating how their expression patterns relate to the origin of the cancer cells and their potential as drug targets. By understanding their involvement in the molecular mechanisms of ovarian cancer, we can pave the way for more effective and personalized therapies.

PAX2 and PAX8: A Tale of Two Proteins in Ovarian Cancer

PAX2 shield vs PAX8 sword in ovarian cancer

Researchers have been studying the roles of PAX2 and PAX8 in the development and progression of HGSC. PAX8 is expressed in HGSC tumors derived from both the fallopian tube and the ovarian surface epithelium (OSE), suggesting a broad role in tumor development, while PAX2's presence diminishes early in cancer development. Understanding this divergence is crucial.

The contrasting behavior of PAX2 and PAX8 raises important questions about their roles in cancer development:

PAX8: Promotes tumor cell growth, migration, and survival. It achieves this by increasing the transcription of genes like p53 and E2f1, which regulate cell cycle and growth.
PAX2: Acts as a tumor suppressor. When re-expressed in ovarian cancer cells (derived through loss of Pten), it inhibits their ability to form tumors and extends survival. Its loss is linked to an increase in stem cell-like characteristics in cancerous cells, contributing to tumor aggressiveness.

The differential regulation of PAX2 and PAX8 in HGSC highlights their potential as therapeutic targets. Exploiting the dependence of HGSC on PAX8, while restoring PAX2 function, could offer a powerful strategy to combat this deadly disease.

Targeting PAX Proteins: A Promising Future for Ovarian Cancer Therapy

The unique characteristics of PAX2 and PAX8 offer opportunities for targeted cancer therapies. PAX8, with its involvement in tumor growth and survival, can be a target for therapies aimed at reducing its activity or disrupting its interactions with other proteins.

Conversely, strategies to restore PAX2 expression in tumors where it has been lost could also prove beneficial. Luteolin, a small molecule, has shown promise in restoring PAX2 expression in certain cell types, although further research is needed to determine its effectiveness in HGSC.

Ultimately, understanding the intricate interplay of PAX2 and PAX8 in ovarian cancer holds the key to developing more effective and personalized treatment strategies, offering hope for improved outcomes and survival for women facing this challenging disease.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.3390/cancers10080262, Alternate LINK

Title: Unpaxing The Divergent Roles Of Pax2 And Pax8 In High-Grade Serous Ovarian Cancer

Subject: Cancer Research

Journal: Cancers

Publisher: MDPI AG

Authors: Laura Hardy, Amrita Salvi, Joanna Burdette

Published: 2018-08-08

Everything You Need To Know

Where does high-grade serous ovarian cancer originate, and why is this important?

High-grade serous ovarian cancer, or HGSC, has traditionally been thought to originate in the ovaries. However, current research indicates that the fallopian tubes are often the primary source of this cancer. Understanding the origin is crucial because proteins like PAX2 and PAX8, which are involved in fallopian tube development, play different roles in cancer progression. Targeting these proteins based on the cancer's origin could lead to more effective treatments.

What are PAX2 and PAX8, and how do they function in ovarian cancer?

PAX2 and PAX8 are transcription factors, meaning they regulate gene expression. PAX8 is often present in HGSC tumors and promotes tumor cell growth, migration, and survival by increasing the transcription of genes like p53 and E2f1. PAX2, on the other hand, often diminishes early in cancer development and acts as a tumor suppressor. The contrasting behavior of these two proteins makes them potential targets for new therapies.

How does PAX8 contribute to tumor development in high-grade serous ovarian cancer?

PAX8 promotes tumor cell growth, migration, and survival in HGSC. It achieves this by increasing the transcription of genes like p53 and E2f1, which are involved in regulating the cell cycle and growth. By targeting PAX8, therapies could potentially disrupt these processes and inhibit tumor progression. However, further research is needed to fully understand the downstream effects of PAX8 inhibition.

What role does PAX2 play in suppressing tumors in ovarian cancer?

PAX2 acts as a tumor suppressor in ovarian cancer cells. Re-expressing PAX2 in these cells can inhibit their ability to form tumors and extend survival. The loss of PAX2 is also linked to an increase in stem cell-like characteristics in cancerous cells, which contributes to tumor aggressiveness. Restoring PAX2 function could be a valuable strategy to combat HGSC, but the mechanisms of PAX2 loss need to be better understood.

How can PAX2 and PAX8 be targeted for ovarian cancer therapy?

Targeted therapies for HGSC could involve reducing the activity of PAX8 or disrupting its interactions with other proteins, given its role in promoting tumor growth and survival. Simultaneously, restoring PAX2 function, which acts as a tumor suppressor, could offer a dual approach. Further research is needed to develop specific drugs that can effectively target PAX8 and restore PAX2 function without causing significant side effects.