Investigating cancer’s partners in crime: the microenvironment

All criminals have their sidekicks who help them carry out their bad deeds. Cancer cells grow and replicate in much the same way—with the assistance of their surrounding environment.

This so-called “tumor microenvironment” is receiving increasing attention from the global community of research scientists. One of new, young leaders in this field is Dr. Ruth Scherz-Shouval, who joined the Weizmann Institute in 2015 after a postdoctoral fellowship at Massachusetts Institute of Technology (MIT).

The question she is pursuing is how cancer cells recruit and subvert normal cells to create an environment that promotes tumor progression and metastasis. What is known, so far, is that cancer cells activate normal, surrounding cells to form blood vessels and connective tissue and to fight the immune system. She wants to know, specifically, which mechanisms are at work throughout this process.

Dr. Scherz-Shouval did her PhD studies at the Weizmann Institute under the guidance of Prof. Zvulun Elazar, an expert in the process of autophagy—the ability of the body’s cells to discard or recycle defective or toxic materials. She made a major contribution to the field of autophagy by unraveling a novel mechanism of regulation of autophagy, mediated by reactive oxygen species such as hydrogen peroxide. Then she did a first postdoctoral fellowship with Prof. Moshe Oren, an expert in cancer research who is now head of the Moross Integrated Cancer Center.

For her second postdoc, at the Whitehead Institute for Biomedical Research at MIT, she received a grant from the Israel National Program for Advancing Women in Science led by the Weizmann Institute. The grant, given to 10 outstanding women scientists to conduct postdoc studies abroad, is given in addition to postdoc salaries and is meant to help women and their families manage with the financial pressures typical of a postdoc period. In addition, she received the Human Frontiers fellowship and a Fulbright award.

With the understanding that tumors are complex organs that are highly dependent on normal cells in their environment, Dr. Scherz-Shouval decided to pursue this line of study further and moved to Boston to do postdoctoral research at MIT. There, she set out to study the tumor microenvironment. She zeroed in on the heat shock response that cells activate when subject to thermal stress such as fever occurring following inflammation, and identified a new role for the “master regulator” of this response, heat-shock factor 1 (HSF1), in the tumor microenvironment. She found that HSF1 plays a vital role in the tumor microenvironment and showed how HSF1 helps reprogram fibroblasts, the cells responsible for making the extracellular matrix and collagen in a tumor’s nearby tissues, causing them to support the tumor’s malignancy.

In collaboration with clinicians at the Brigham and Women’s Hospital and Beth Israel Hospital in Boston and Rabin Medical Center in Israel, clinical studies confirmed that in early-stage breast and lung cancer, high stromal HSF1 activation is strongly associated with poor patient outcome, a finding that has significant diagnostic and therapeutic implications. Her research may also have implications for inflammation more generally, in particular inflammatory bowel disease (IBD).

In her new lab at the Weizmann Institute, she is broadening her work on how stress responses rewire and reshape the tumor microenvironment, creating a tumor-supportive environment that drives progression and metastasis.

 

Dr. Ruth Scherz-Shouval is supported by the Laura Gurwin Flug Family Fund, the Peter and Patricia Gruber Awards, the Dr. Zwi & Amelia Steiger Cancer Research Fund, the Eugene & Emily Grant Family Foundation, the David M. Polen Charitable Trust, Hilda Namm, Larkspur, CA, and the Estate of Annice Anzelewitz.

 

Dr. Ruth Scherz-Shouval