Preferred Label : Racemetyrosine/Methoxsalen/Phenytoin/Sirolimus;
NCIt synonyms : Tyrosine Isomers/Phenytoin/Methoxsalen/Sirolimus; SM-88/Methoxsalen/Phenytoin/Sirolimus; SM-88 Used with Methoxsalen/Phenytoin/Sirolimus; SM-88 Used with MPS; Racemetyrosine/Methoxsalen/Phenytoin/Sirolimus Combination;
NCIt definition : A combination agent containing racemetyrosine, methoxsalen, phenytoin and sirolimus,
with potential antineoplastic activity. Upon administration of racemetyrosine/methoxsalen/phenytoin/sirolimus
SM-88, racemetyrosine, being a dysfunctional and modified form of the non-essential
amino acid tyrosine, is specifically taken up by cancer cells through the transporter
L-amino acid transferase-1 (LAT1; CD98). As a tyrosine derivative and faulty amino
acid protein building block, racemetyrosine prevents protein synthesis in cancer cells.
Specifically, this prevents mucin-1 (MUC1) protein synthesis. MUC1 is highly overexpressed
by most cancer cells and regulates the increased reactive oxygen species (ROS) in
cancer cells created from the altered metabolism that cancer cells utilize, by upregulating
key antioxidant defenses and preventing ROS-mediated apoptosis. In the absence of
MUC1, ROS levels are increased, leading to an increase in oxidative stress, and induction
of apoptosis. Also, being a protective transmembrane protein, MUC1 is part of the
protective layer on the outside of cancer cells and plays a key role in shielding
the cancer cell from the immune system. The loss of MUC1 compromises the cell membrane,
thereby making the cancer cell more vulnerable to be recognized and attacked by the
immune system. Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, increases
the cancer cells' need for tyrosine uptake and increases the uptake of racemetyrosine
by LAT1. Phenytoin stimulates the release of reactive lipid species by the liver which
accumulate in the tumor microenvironment (TME) and are taken up by cancer cells, thereby
further increasing ROS within the cancer cell and increasing oxidative-related apoptosis.
Mehoxsalen promotes toxic electron transfer and increases melanin, increases oxidative
reactions and production of ROS. This further stimulates oxidative stress-mediated
apoptosis. Normal cells do not regularly take up certain non-essential amino acids,
such as tyrosine, but readily convert phenylalanine to tyrosine, so normal healthy
cells are not expected to consume racemetyrosine.;
NCI Metathesaurus CUI : CL498405;
Origin ID : C124051;
UMLS CUI : C5554533;
Semantic type(s)
- concept_is_in_subset
- has_target
