Dr Luis A. Gomez-Sarosi discusses how cancer therapies interact with cancer and non-cancerous cells in the tumour microenvironment and how they respond to treatment.
Solid tumours are composed of an array of different types of cells which include cancer or malignant cells and non-cancerous or normal cells, such as fibroblasts and immune cells. This complex mass is known as the tumour microenvironment. When treated with anti-cancer therapies, normal cells can also be exposed to the treatment generating a cellular response that impacts tumour cell behaviour.
DNA damage secretory program (DDSP)
Cancer treatments which target the genetic material of the cells or DNA initiate a cellular response in the microenvironment, which includes the secretion of different factors ultimately affecting cancer cells in a variety of ways including proliferation increase, enhance of invasion potential and therapy resistance.
How cancer research is conducted in such complex environments?
Initially, in order to understand the role of normal cells such as fibroblasts and their response to DNA targeted therapies in terms of induction or not of DDSP; active proliferating fibroblasts were studied in vitro using gene expression profiling to understand which genes are been activated or deactivated as a consequence of the treatment. However, fibroblasts do not exhibit active growth under physiological conditions. For this reason, we determined the gene expression profile mentioned previously in non-proliferating fibroblasts.
What was found in this study and what are the implications to improve cancer treatment?
We found that the gene expression profile as a consequence of cancer treatment in non-proliferating or quiescent fibroblasts is pretty similar to the profile of proliferating fibroblasts. The quiescent cells showed an augmented expression of growth factors (cell proliferation activators) and other proteins called cytokines. These factors increased proliferation, cell invasion, promoted survival and therapy resistance in prostate cancer cells.
These findings showed an induction of DDSP in the quiescent fibroblasts by cancer treatments which increment the aggressiveness of the cancer cells. This implies the urgent need of developing therapeutic approaches directed to suppress the secretory program to improve the effectiveness of cancer therapies.
Cutting-Edge Innovation to improve early cancer detection and survival
2017 marked the year when more than 20 professionals from different educational backgrounds and nationalities across Europe were selected by the European Institute of Innovation and Technology (EIT); Innovation Community EIT Health, to be part of the new innovation fellowship program “StarShip” to begin a journey to develop disruptive technologies to address current healthcare challenges that Europe and the rest world are facing.
Multidisciplinary teams were formed and the Stanford Biodesign innovation process was learned and implemented to observe, find and identify unmet needs in the clinical environment. Simultaneously, specific industry challenges were provided by General Electric (GE) Healthcare (Hungary) to give an applied context to the work in progress.
Our innovative solution
Our team, Nebula-X, designed an innovative medical solution to detect colorectal polyps (which can evolve to cancer) to overcome the current polyp miss rate of 22%, providing a safe and comfortable approach comparing to colonoscopies as preferred procedure.
During November 2017, the last workshop of StarShip in Budapest, Hungary took place. There, all teams presented their innovative solutions and, after the deliberation of a jury integrated by GE Healthcare executives, our team was selected as the winner of the competition. Now we are dedicated to translate this innovative design into a medical device with the solid purpose of significantly increase the accuracy of polyp detection, as well as, patient survival.
 Gomez-Sarosi L., et al. DNA Damage Induces a Secretory Program in the Quiescent TME that Fosters Adverse Cancer Phenotypes. Molecular Cancer Research. 2017 Jul;15(7):842-851. doi: 10.1158/1541-7786.MCR-16-0387.
 2017 Teams and Projects. StarShip Innovation Fellowship Program – EIT Health. https://www.starship.eithealth.eu/starship-2017/
Luis is a cancer biology research scientist, who combines his scientific background with business knowledge, innovation and entrepreneurship to develop solutions in health technology innovation.