Exciting advancements have emerged from the German Cancer Research Center in collaboration with the Heidelberg Stem Cell Institute (HI-STEM) and the NCT Heidelberg, heralding a new era in metastatic breast cancer research.
Researchers have made a ground-breaking leap by successfully growing stable tumor organoids directly from the blood of patients battling breast cancer.
This innovation is a game changer, as circulating tumor cells (CTCs)—the building blocks of metastasis—are typically rare and have remained largely unmanageable in laboratory settings until now.
Through these mini-tumors, the research team is gaining critical insights into the molecular pathways that fuel the survival and treatment resistance of these cancer cells, which could lead to novel therapeutic strategies.
Understanding Metastatic Breast Cancer
Metastatic breast cancer, notorious for its ability to spread to vital organs such as the liver, lungs, and brain, continues to pose significant treatment hurdles despite remarkable strides over the years.
While certain therapies can initially reduce metastases, the effect often fades, highlighting an urgent need for more effective treatment modalities.
The journey of metastasis begins when cancer cells break away from the primary tumor, entering the bloodstream where they face billions of ordinary blood cells.
Previous studies suggested that only a small fraction of CTCs have the potential to establish new metastatic sites, making them extremely difficult to isolate and culture.
One of the lead researchers pointed out the importance of understanding how these resilient cells survive therapy, as this knowledge could be key to combating their resistance and potentially thwarting metastasis before it starts.
Groundbreaking Innovations in Tumor Cultivation
The team’s remarkable achievement involved directly cultivating CTCs from patient blood samples, eliminating the time-intensive requirement of growing these cells in immunocompromised mice.
This new method simplifies the process, allowing for the ongoing collection of tumor material without the need for invasive tissue biopsies.
By creating patient-specific, three-dimensional organoids from blood samples, researchers can delve deeper into the molecular mechanisms that enable tumors to endure treatments.
Additionally, these organoids provide an efficient platform for assessing the effectiveness of existing cancer therapies in a controlled laboratory environment.
In conjunction with the CATCH clinical trial at NCT Heidelberg, the research has delved into the genetic diversity of breast cancer cells.
The successful cultivation of organoids has unveiled a significant signaling pathway that supports the growth of CTCs in circulation.
The protein NRG1 plays a crucial role, binding to the HER3 receptor and activating pathways that foster cell survival and growth.
Notably, the study revealed that when NRG1 is depleted or its receptors blocked, CTCs can shift to an alternative signaling pathway via FGFR1 as a compensatory mechanism.
Future Directions and Personalized Therapies
Roberto Würth, a key contributor to the study, emphasized that this adaptability showcases a fundamental resistance mechanism, where cancer cells frequently tap into bypass pathways when faced with targeted treatments.
Encouragingly, the researchers discovered that simultaneously inhibiting both the NRG1-HER2/3 and FGFR pathways can effectively halt tumor growth and induce cell death.
Andreas Trumpp, who leads this extensive research initiative, expressed enthusiasm about cultivating tumor organoids from blood samples taken at various stages of a patient’s treatment journey.
This methodology represents a significant leap forward, making it easier to investigate the mechanisms behind therapy resistance and facilitating the creation of new treatments aimed at resistant tumor cells.
Moreover, these customized organoids may lead to personalized therapeutic strategies, potentially reducing the risk of developing resistance and metastasis.
Before this promising innovation can transition into clinical practice for breast cancer treatment, further validation through clinical trials will be necessary.
Source: ScienceDaily