During Development, Cells Grow, EXPAND, And Migrate to Generate Tissues and Organs in a Highly Controlled Manner. Many Intracellular Pathways-Series of Signaling Cascades with a Cell-Regulate these Actions to Avoid Non-Programmed Growth that Cold Lead to Malformations OR CANCER. One of these pathways is the pten / pi3k axis, a complex series of perfectly balanced chemical reactions.

Mutations in the Pten Gene Usually Result in the Overactiveation of Pi3k and the Imbalance of the system. This may trigger the onset of different types of cancer, like breast and prostate, and when presented in the Germline, cause several disorders. From the clinical personal percective, these disorders Addressed, mainly due to a poor understanding of the disease. Precisely, the Limited Understanding of the Origin of Phts-Related Phenotypes has implemented the development of preclinical models and the implementation of molecular therapies.

What scientists do know is that pi3k mutations affecting endothels, the ones lining the inner layer of blood vessels, lead to vascular malformations. Not surprisingly, up to 50% of phts patients also develop vascular malformations during early children. These lesions are associated with Severe Pain and Swelling, with Surgery and Embolization -the deliberate blocking of the affected vessels-s the main theraputic strategies. However, depending on the localization and extension, these strategies might not be possible, leaving patients without any other therapeutic option.

The endothelial pathobiology and microenvironment group at the josep carreras institute, LED by Dr. Mariona Graupera TogeTher with Dr. Sandra Castillo, Former Lab Member and Current Researcher at SDJ Pediatric Cancer Center Barcelona, ​​and Dr. Eulàlia baselga, head of the pediatric dermatology unit at hospital sant joan deu, have investigated the genetic cause of phts-Related Vascular Malformations.

After a thorough analysis of biopsies and patients and patients, they discovered that phts patients had replaced one of their functional ptenal copies with a non-functional one, in aus “Uniparental disomy.” In a series of experiences in mice, they demonstrated that this alternation could expert most of the effects seen affections in the vasculature.

This genetic discovery, recently Published in Cancer discovery Has Allowed them to Generate the first mouse model of phts-Related Vascular Malformations and Use it as a Benchmark to Study The Effects of Two ANTICANCER DRUGS KNOWN to Counterbalance Action, Action, would do if present.

The Studies have identified that blocking pi3k downstream efforts – Down in the metabolic Cascade – With RAPAMYCIN or CapivasertiB Inhibitors Significhales Vascular Growth. However, the Specific Inhibition of Pi3K with Alpelisib Gives No Substantiial Benefit. Given these results, the team provides, as proof-of-concept for Clinical Activity, The off-Label Treatment with RAPAMYCIN OF STWO PATENS with PHTS who Indeed Showed VASCUD VASCUD VASCUD VASCUD Abrogated Lesion -ssociated Pain.

These new findings are of paramount importance since the ability to stop pHTS Effects from the very bets from the need to be greatly improved improves’ Survival and Quality of Life. Also, phts is usually diagnosed when cancer has alredy grown in adults. Given that Vascular Malformations are pediatric manifestations of phts, we berieve that this offers a unique clinical options for early diagnosis.