Metastatic Breast Cancer

Scientists uncover how spreading cancer adapts to its environment

October 12, 2016

Spreading tumor cells are able to adapt their metabolism to the specific organs they are invading. This conclusion forms the gist of a VIB-KU Leuven paper published in the renowned scientific journal Cell Reports. The researchers examined lung cancer metastases that originated from breast tumors, discovering that the two tumors have different ways of converting nutrients into biomass building blocks. Thanks to these findings, scientists may be able to develop new therapies that target the metabolism of cancer cells, thereby halting a tumor’s growth.

When the Belgian research group of professor Sarah-Maria Fendt (VIB-KU Leuven) started this project, their choice to examine breast cancer that had spread to the lungs was no coincidence. Although fewer and fewer people die from breast cancer – thanks to both increased screening and improved treatment – a breast tumor’s spread to other organs causes a whopping 90% of all deaths caused by breast cancer. In addition, only 22% of all patients with spreading or ‘metastatic’ breast cancer survive.

Environment overrides genetics

According to today’s models, genetic aberrations define how cancer cells convert nutrients (carbohydrates, fats and proteins) from their environment into biomass building blocks in order to grow. As a result, the treatment of breast cancer metastases (the cancer’s new occurrences in other organs) is currently based on the genetic background of the primary breast tumors. However, these treatments often fail. The study by prof. Fendt might just have uncovered a key element in this issue.

Prof. Sarah-Maria Fendt (VIB-KU Leuven): "There are two major metabolic pathways used by cells to generate biomass building blocks for tumor growth. We discovered that in vivo cancer cells in secondary lung tumors are more prone of using one of these two systems compared to the primary breast cancers. This is a response to subtle changes in the lung microenvironment that override the influence of cancer-specific genes."

Some cancer therapies directly target tumor cell metabolism, but this study implies that cancer metastases should be treated with different drugs than the primary cancers.

Prof. Sarah-Maria Fendt (VIB-KU Leuven): "In time, our findings may be put to use in patients with advanced breast cancer. But first, we will follow the basic lanes and investigate which other metabolic pathways are impacted by the tumor microenvironment. We will also examine the role of the microenvironment at the point when the cancer starts spreading. In this way, we are gradually throwing more light on all the parameters of tumor growth – a crucial information needed for developing more precise and effective anti-cancer therapies."

Article: Breast cancer-derived lung metastases show increased pyruvate carboxylase-dependent Anaplerosis, Sarah-Maria Fendt et al., Cell Reports, published 11 October 2016.

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