New Compound Targets Metastatic Cancer Cells - NFCR

Blog

New Compound Targets Metastatic Cancer Cells

TEL-AVIV​ ​—​ ​Scientists​ ​at​ ​Bar-Ilan​ ​University​ ​in​ ​Israel​ ​successfully​ ​targeted​ ​and​ ​rendered​ ​inert​ ​the​ ​enzyme that metastatic​ ​cancer​ ​cells​ ​need​ ​to​ ​survive​ ​in​ ​the​ ​body​ ​once​ ​they​ ​have​ ​left​ ​their​ ​host​ ​tumor.​ ​The​ ​findings​ ​of Professor​ ​Uri​ ​Nir,​ ​of​ ​the​ ​Mina​ ​and​ ​Everard​ ​Goodman​ ​Faculty​ ​of​ ​Life​ ​Sciences​ ​at​ ​Bar-Ilan​ ​University,​ ​and​ ​his team​ ​could​ ​pave​ ​the​ ​way​ ​to​ ​therapies​ ​that prevent metastasis, or the spreading of​ ​cancer​ ​cells from their point of origin. 

Nir​ ​and​ ​his​ ​team​ ​discovered​ ​the​ ​existence​ ​of​ ​an​ ​enzyme,​ ​FerT,​ ​in​ ​the​ ​mitochondria​ ​of​ ​cancer​ ​cells​ ​that is not​ ​present in those​ ​of​ ​normal​ ​cells​ ​(mitochondria​ ​are​ ​the​ ​“power​ ​generators”​ ​of​ ​a​ ​cell).​  ​Once​ ​free​ ​within​ ​the​ ​body, metastatic​ ​cancer​ ​cells​ ​face​ ​an​ ​environment​ ​short​ ​on​ ​the​ ​nutrients,​ ​such​ ​as​ ​glucose,​ ​needed​ ​to​ ​survive and grow;​ ​FerT kicks​ ​ ​the​ ​cancer’s​ ​mitochondria​ ​ into​ ​high​ ​gear​ to​ ​produce​ ​energy​ ​when​ ​the​ ​given​ ​environment​ ​lacks​ ​the necessary​ ​metabolic​ ​components​ ​for​ ​survival.​ ​Basically,​ ​it​ ​makes​ ​mitochondria​ ​do​ ​more​ ​with​ ​less. Interestingly,​ ​this​ ​is​ ​what​ ​FerT​ ​does​ ​in​ ​another​ ​cell​ ​that​ ​must​ ​survive​ ​outside​ ​its​ ​origin:​ ​sperm. 

 “Like​ ​metastatic​ ​cells,​ ​sperm​ ​cells​ ​are​ ​unique​ ​in​ ​that​ ​they​ ​can​ ​also​ ​generate​ ​energy​ ​under​ ​very​ ​harsh conditions.​ ​Once​ ​they​ ​have​ ​entered​ ​the​ ​female​ ​birth​ ​canal,​ ​where​ ​there​ ​is​ ​no​ ​blood​ ​supply​ ​for​ ​them,​ ​they produce​ ​and​ ​expend​ ​enormous​ ​amounts​ ​of​ ​energy​ ​under​ ​very​ ​extreme​ ​or​ ​abnormal​ ​conditions,”​ ​explains Nir.​ ​“We​ ​found​ ​that​ ​very​ ​aggressive​ ​metastatic​ ​cancer​ ​cells​ ​looked​ ​for​ ​and​ ​identified​ ​this​ ​sperm-specific protein,​ ​learned​ ​how​ ​to​ ​produce​ ​it,​ ​and​ ​harnessed​ ​it​ ​in​ ​order​ ​to​ ​potentiate​ ​their​ ​mitochondria​ ​and​ ​produce energy​ ​under​ ​very​ ​harsh​ ​conditions.” 

With​ ​this​ ​information,​ ​Nir​ ​developed​ ​a​ ​compound​ ​dubbed​ ​E260.​ ​When​ ​applied​ ​to​ ​metastatic​ ​cells​ ​in​ ​culture or​ ​mice​ ​with​ ​metastatic​ ​tumors,​ ​E260​ ​enters​ ​the​ ​metastatic​ ​cells​ ​and​ ​then​ ​​ ​the​ ​mitochondria,​ ​whereupon it​ ​binds​ ​to​ ​FerT,​ ​distorting​ ​its​ ​energy-generating​ ​activity​ ​to​ ​such​ ​a​ ​degree​ ​the​ ​mitochondria​ ​effectively​ ​shuts down.​ ​Metastatic​ ​cells​ ​are​ ​notoriously​ ​tenacious;​ ​they​ ​can​ ​detect​ ​damage​ ​to​ ​their​ ​mitochondria​ ​and​ ​even​ ​take steps​ ​to​ ​repair​ ​them.​  ​ Nir found that E260-applied​ ​cells​ ​did not have ​the​ ​energy​ ​necessary to​ ​both​ ​repair​ ​mitochondrial function​ ​and​ ​maintain​ ​other​ ​cell​ ​processes​ ​at​ ​the​ ​same​ ​time.​ ​The​ ​result: cell death. 

More​ ​promisingly,​ ​“We​ ​have​ ​treated​ ​mice​ ​with​ ​metastatic​ ​cancer​ ​and​ ​this​ ​compound​ ​completely​ ​cured them​ ​with​ ​no​ ​adverse​ ​or​ ​toxic​ ​effect​ ​that​ ​we​ ​can​ ​see.​ ​We​ ​have​ ​also​ ​checked​ ​several​ ​normal​ ​cells​ ​and​ ​they are​ ​not​ ​affected,”​ ​says​ ​Nir.

E260​ ​came​ ​about​ ​from​ ​the​ ​fact​ ​that​ ​cancer​ ​can​ ​most​ ​often​ ​be​ ​successfully​ ​treated​ ​in​ ​its​ ​early​ ​stages​ ​when confined​ ​to​ ​one​ ​organ. ​ ​While​ ​standing​ ​immunotherapy​ ​can​ ​be​ ​effective​ ​in​ ​treating​ ​the metastatic​ ​phase​ ​of​ ​the​ ​disease,​ ​only​ ​a​ ​limited​ ​number​ ​of​ ​patients​ ​fit​ ​the​ ​criteria​ ​for​ ​such.​ ​Generally speaking,​ ​once​ ​a​ ​cancer​ ​metastasizes,​ ​treatment​ ​becomes​ ​more​ ​difficult​ ​and​ ​mortality​ ​much​ ​higher. 

Nir​ ​and​ ​his​ ​team​ ​hope​ ​to​ ​pursue​ ​Phase​ ​1​ ​clinical​ ​trials​ ​within​ ​a​ ​year-and-a-half.​ ​The​ ​research​ ​was published​ ​this​ ​month​ ​in​ ​the​ ​journal​ ​​Nature​ ​Communications.

Post a comment