Mid-Term Report Summary - STROMALIGN (Mechanisms and Targeting Stromal Contribution to Tumour Invasion and Metastasis)
Tumor growth is typically dependent on the formation of new blood vessels to supply nutrients and oxygen to the growing neoplastic mass. This phenomenon, known as angiogenesis, can be inhibited with current anticancer drugs, known as anti-angiogenics, in order to impede tumor nurture and growth. Indeed, it has been shown that inhibition of this process is a successful strategy in the treatment of various cancers increasing patient survival.
Studies in animal models of cancer in mice demonstrate the benefits of this therapy on survival and anti-tumor effects. Nevertheless, it has been shown that these therapies also cause an increase in the tumor aggressiveness, producing increased local invasion and tumor dissemination to other organs, known as metastasis.
During the development of this project, we have done three breaking advances in the knowledge of tumor aggressiveness after antiangiogenics:
1. We have identified several genes and cellular mechanisms that are involved in the pro-invasive signaling and might be responsible for this enhanced aggressive phenotype.
2. Current knowledge in the field suggested that lack of oxygen (hypoxia) was the main initial trigger of the enhanced aggressive phenotype. Nevertheless, we have recently described that this process can occur through a hypoxia-independent mechanism that implicates white blood cells from the immune system.
3. By using a novel platform of patient-derived models of cancer in mice (Tumorgrafts) we have discovered that tumor stroma, the non-neoplastic supportive surrounding tissue, is key for the initiation of tumor invasion and metastasis.
We are currently validating these two scientific advances to the clinical setting utilizing tumor samples from patients in our Hospital that are treated with anti-angiogenic therapies. With this information we will be able to find new markers and targets of tumor aggressiveness that will ultimately benefit anti-angiogenic treated patients in the clinic.
Studies in animal models of cancer in mice demonstrate the benefits of this therapy on survival and anti-tumor effects. Nevertheless, it has been shown that these therapies also cause an increase in the tumor aggressiveness, producing increased local invasion and tumor dissemination to other organs, known as metastasis.
During the development of this project, we have done three breaking advances in the knowledge of tumor aggressiveness after antiangiogenics:
1. We have identified several genes and cellular mechanisms that are involved in the pro-invasive signaling and might be responsible for this enhanced aggressive phenotype.
2. Current knowledge in the field suggested that lack of oxygen (hypoxia) was the main initial trigger of the enhanced aggressive phenotype. Nevertheless, we have recently described that this process can occur through a hypoxia-independent mechanism that implicates white blood cells from the immune system.
3. By using a novel platform of patient-derived models of cancer in mice (Tumorgrafts) we have discovered that tumor stroma, the non-neoplastic supportive surrounding tissue, is key for the initiation of tumor invasion and metastasis.
We are currently validating these two scientific advances to the clinical setting utilizing tumor samples from patients in our Hospital that are treated with anti-angiogenic therapies. With this information we will be able to find new markers and targets of tumor aggressiveness that will ultimately benefit anti-angiogenic treated patients in the clinic.