Our necrosis platform
About Necrosis
Necrosis is a form of cell death which occurs exclusively in pathological situations due to cell injury. Necrosis for instance occurs in myocardial infarction, cerebral infarction, gangrene, diabetes, hypoxia, intoxication, burns and radiation. Also, aggressively growing tumors and metastasis spontaneously develop necrotic cores. Due to poor blood flow there is lack of oxygen, which causes that the cell dies. In general necrosis is related to a medical indication, a healthy human body does not contain necrosis. Necrosis is the unprogrammed cell death in which the cell dies and the cell membrane loses its integrity. This loss of membrane integrity is essential because then the internals of the cell, including the cytoskeleton of the cell, becomes available for targeting by coretags' necrosis targeting molecule. Necrosis should not be confused with apoptosis which is the natural and programmed process of cell renewal. Every day our body contains billions of apoptotic death cells which are cleaned up by macrophages. In apotosis the cell membrane stays intact which means the necrosis targeting molecule is not binding to apoptotic cells.
Almost all solid tumors, especially when they grow fast and aggressive, develop necrotic cores due to poor blood flow and lack of oxygen. This means that the degree of the spontaneous necrosis in tumors is correlated with poor prognosis.
Stem cells in the necrotic cores
Recent studies show that cancer stem cells or cancer initiating cells residing in necrotic cores and the rim of the solid tumor. Because conventional radiotherapy and chemo- or immunotherapy have no effect in the necrotic cores, due to lack of oxygen or poor blood flow, these stem cells survive treatment which make it possible that the cancer e seems to be treated but later returns after a certain period of time when the stem cells get active again. Coretag aims to kill also these stem cells holding up in the necrosis and the rim of the solid tumor with its necrosis targeting radiotherapy.
In cancer there are two origins for tumor necrosis:
a. Natural Necrosis
Malignant tumors develop necrosis because of their fast und unbridled growth and the unstructured construction of blood vessels in tumors. In these tumors and metastases there is not enough blood flow and oxygen, causing tissue to die and become necrotic.
b. Therapy induced necrosis
Most of the existing anti-cancer therapies, like chemo- immuno- and radiotherapy focus on killing cancer cells. Which means that after inducing this necrosis, the necrosis targeting radiotherapy has more necrosis to target, which improves the effect.
Necrosis as a holy grail
Many successful modern cancer therapies are based on receptors and targeting of specific types of living cancer cells. Because there are over 100 different cancer types and any tumor is heterogeneous, which means a solid tumor contains different cancer types, it is hard to find an effective treatment. Because of the correlation between aggressiveness of solid tumors and the development of necrotic cores, necrosis provides a generic target for targeted radiotherapy which works in every solid tumor and metastasis no matter how heterogeneous the tumor is or what receptors the living cancer cells have. Because of these generic moieties necrosis as a target is very interesting and provides tremendous increase of treatment options. Especially in situations where surgery or other therapies are no longer are no longer valid options for treatment, the targeting of the necrotic cells could work. Although the importance of necrosis targeted therapy is recognized for decades, until Coretag no one discovered or developed a necrosis targeting compound which was non-toxic, is a small molecule, is a chemical compound which can be produced under GMP standards or does have a free group to make it possible to connect the targeting molecule to an chelator for holding the nuclear isotope.
