Tag: ER+ breast cancer

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How Breast Cancer Cells Survive in Bone Marrow after Remission

On By ModernMedia
Photo by National Cancer Institute on Unsplash

A new study has shed light on a previously poorly understood aspect of breast cancer recurrence: how cancer cells survive in bone marrow despite targeted therapies. The paper appears in the Journal of Clinical Investigation. 

Oestrogen receptor positive (OR+) breast cancer is the most common form of the disease, and cancer cells of this kind can live for years in bone marrow after remission. The persistence of these cells in marrow leads to the disease recurring about 40% of patients. This return can take the form of especially aggressive bone cancer with symptoms such as bone fractures and hypercalcaemia. 

The cells can also spread to other organs, causing recurrent disease that is currently incurable. 

To better understand how these cancer cells survive, and why they cause such aggressive returning disease, researchers investigated what happens to these dispersed cells in bone marrow. 

Their key finding was the mechanism by which a normal cell type, mesenchymal stem cells, in the bone marrow supports the cancer cells.

“We discovered that the breast cancer cells require direct contact with mesenchymal stem cells,” said Gary Luker, MD, senior author on the paper.  

“The cancer cells physically borrow molecules – proteins, messenger RNA – directly from the mesenchymal stem cells. Essentially the mesenchymal stem cells act as very generous neighbours in donating things that make the cancer cells more aggressive and drug resistant.”

In laboratory experiments, contact between cancer cells and mesenchymal stem cells induced changes in hundreds of proteins. Further analysis of which proteins allowed for survival of breast cancer cells led researchers to focus on GIV, also known as Girdin. The paper notes that GIV drives “invasiveness, chemoresistance, and acquisition of metastatic potential in multiple cancers.”

GIV makes these cancer cells specifically resistant to oestrogen-targeted therapies, such as the drug Tamoxifen. The researchers hope this understanding of the mechanism of cancer cell survival will one day lead to treatments that prevent OR+ breast cancers from returning.

Sleeper cells can awaken

“Sleeper cells can be reawakened and cause oestrogen receptor positive breast cancers to relapse years –in some cases as long as a decade – after patients were believed to be in remission,” said study author Pradipta Ghosh, M.D., a professor in the Departments of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine.

“Since these cancer cells ‘borrow’ essential proteins from stem cells in the bone marrow through cellular tunnels – much like smuggling – approaches for targeting the tunnels or proteins they smuggle could help prevent the relapse and metastasis of oestrogen receptor positive breast cancer.”

Source: University of Michigan

Categories : CancerTags :

New Trial Flips the Script for Hormonal Treatment of Breast Cancer

On By ModernMedia
Photo by National Cancer Institute

For decades, hormonal treatment of breast cancer has been going in one direction: blocking oestrogen. Now, a global study has discovered there may be another, less toxic way to defeat the most common form of breast cancer. The results, published in The Lancet Oncology, showed that the androgen receptor (AR) agonist enobosarm, is effective against oestrogen receptor-positive (ER+) breast cancer, which constitutes up to 80% of all breast cancer cases.

“The effectiveness of enobosarm lies in its ability to activate the AR and trigger a natural defence mechanism in breast tissue, thereby slowing the growth of ER+ breast cancer, which relies on the hormone oestrogen to grow and spread,” said senior co-author Professor Wayne Tilley, Director of the Dame Roma Mitchell Cancer Research Laboratories at the University of Adelaide.

“This clinical study is supported by our pre-clinical research, previously published in Nature Medicine, which established that the AR is a tumour suppressor in both normal breast tissue and ER+ breast cancer.”

Along with investigators from the University of Adelaide and Dana-Farber Cancer Institute (DFCI) in Boston, USA, the international study also included researchers from the University of Liverpool in the UK and other experts around the world.

The team assessed enobosarm’s efficacy and safety in 136 postmenopausal women with advanced or metastatic ER-positive, HER2-negative breast cancer.

Enobosarm showed significant anti-tumour activity and was well-tolerated by patients, without adversely affecting their quality of life or causing masculinising symptoms.

This discovery represents the first advancement in hormonal treatment of ER+ breast cancer in decades and offers a promising new oral treatment strategy for the most prevalent form of breast cancer.

The new hormonal strategy differs from the existing standard-of-care hormonal treatments, which have been around for decades and involve suppressing oestrogen activity in the body or inhibiting the ER.

Although successful initially, treatments targeting ER can cause severe side effects and treatment-resistant progression of the disease is common.

“Our findings are very promising. They demonstrate that stimulating the androgen receptor pathway with enobosarm can be beneficial,” said senior co-author and study Principal Investigator Dr Beth Overmoyer from DFCI.

“This is the first time a non-oestrogen receptor hormonal treatment approach has been shown to be clinically advantageous in ER+ breast cancer. The study supports further investigation of enobosarm in earlier stages of breast cancer as well as in combination with targeted therapies, such as ribociclib, a CDK 4/6 inhibitor.”

estrogen to grow and spread,” said senior co-author Professor Wayne Tilley, Director of the Dame Roma Mitchell Cancer Research Laboratories at the University of Adelaide.

“The data strongly encourages more clinical trials for AR-stimulating drugs in treating AR-positive and ER-positive breast cancer. The fact that this drug is well-tolerated also opens possibilities for its use in breast cancer prevention,” said co-author Dr Stephen Birrell, a clinical affiliate of the University of Adelaide.

Source: University of Adelaide