The un­sta­ble (adult) brain

MRI re­veals changes in early to mid-adult­hood brains

The McGill Daily - - Sci+Tech - Sam Min Sci+tech Writer

Cells in our body usu­ally op­er­ate in an or­derly fash­ion: they di­vide and un­dergo apop­to­sis as the body needs them. How­ever, can­cer­ous cells grow and di­vide un­con­trol­lably; they don’t un­dergo their pro­grammed deaths when they are dam­aged. Can­cer of­ten ap­pears in the form of a mass of can­cer­ous cells, known as a tu­mor. Some can­cers are ma­lig­nant, mean­ing they can break off from their source of ori­gin and in­vade other healthy tis­sues, cre­at­ing havoc and break­ing things one by one. One month a pa­tient might see a mass on their chest, the next the pa­tient might have a hard time breath­ing. The can­cer has spread from one place to an­other, and this is called metas­ta­sis. Can­cers can start any­where in the body: blood, bones, or in­ter­nal or­gans.

The pri­mary can­cer treat­ments are chemo­ther­apy, ra­dio­ther­apy and surgery. How­ever, de­pend­ing on the type of can­cer, one treat­ment may work and an­other may not. Through chemo­ther­apy, an on­col­o­gist ap­plies sev­eral drugs to re­duce and re­move a tu­mor. Dur­ing ra­dio­ther­apy a doc­tor beams ra­di­a­tion to trim down the tu­mor size. Chemo­ther­apy and ra­dio­ther­apy are em­ployed first, fol­lowed by surgery. In surgery, a sur­geon cuts a chunk of the tar­geted or­gan where the tu­mour lies.

Medul­loblas­toma is a can­cer that orig­i­nates in the cere­bel­lum, a part of the brain that co­or­di­nates move­ment and bal­ance. 75% of the af­fected pa­tients are un­der ten years old. Fol­low­ing pri­mary can­cer treat­ments, se­vere side- ef­fects oc­cur in­clud­ing neu­rocog­ni­tive deficits, en­docrine prob­lems, menin­gioma and steril­ity. Many healthy or­gans are sub­ject to toxic dam­age from ses­sions of chemo­ther­apy. This dam­age is even more se­vere in chil­dren be­cause their cells di­vide more quickly, mean­ing the spread of tox­ins is faster. Surgery also car­ries high risks as the cere­bel­lum is lo­cated just above the spinal cord.

To look for al­ter­na­tive treat­ments, a re­search group in Ten­nessee sug­gested a new strat­egy to treat medul­loblas­toma. The Ten­nessee group used a novel mol­e­cule named Hhan­tag691 that blocks a path­way named Sonic Hedge­hog (SHH). When the SHH path­way is ac­tive, the cells in the cere­bel­lum called gran­ule cell pre­cur­sors mul­ti­ply un­con­trol­lably, and medul­loblas­toma ap­pears. Through the ac­tion of Hhan­tag691, the ram­pant pro­lif­er­a­tion stops.

This method was later tested in clin­i­cal tri­als. In 2008, a pa­tient was treated with a sim­i­lar but not iden­ti­cal mol­e­cule to Hhan­tag691 dur­ing clin­i­cal trial phase I - this is the phase when sci­en­tists ap­ply drugs of in­ter­est that they had used on an­i­mals to hu­mans. Be­fore the treat­ment, the can­cer had al­ready spread. Af­ter the treat­ment, the can­cer dis­ap­peared com­pletely in 2 months. Sadly, the pa­tient died 3 months af­ter the treat­ment when the tu­mor re­lapsed. This was be­cause a mu­ta­tion had oc­curred, al­ter­ing the SHH path­way and ren­der­ing the drug in­ef­fec­tive. Al­though un­for­tu­nately the pa­tient did not sur­vive, this was the first suc­cess­ful case of tar­geted-ther­apy, where only one type of can­cer is tack­led.

Pass­ing the four phases of a clin­i­cal trial is re­quired to get a drug ap­proved. Vis­mod­egib, the com­mer­cial name of the drug that has com­pleted the first case of tar­geted ther­apy, is at phase II. In 2015, the drug worked bet­ter in Medul­loblas­toma pa­tients who had a mu­tated SHH path­way than the ones with no mu­ta­tion in the SHH path­way.

Medul­loblas­toma shows how pow­er­ful a can­cer can be. Sci­en­tists have painstak­ingly de­vel­oped new strate­gies to pro­vide tar­get- spe­cific treat­ments against can­cer, but it only takes one mu­ta­tion from a can­cer cell for a pa­tient to be­come drug-re­sis­tant. Per­haps one ob­vi­ous rea­son that can­cer is like a death sen­tence to us is that it morphs our fun­da­men­tal bi­o­log­i­cal pro­cesses to fa­vor it­self. So de­spite ad­vance­ments, it seems can­cer re­search still has a long way to go.

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