Cancer: New tar­get found for drug-re­sis­tant tu­mors

Daily Messenger - - National -

IS­LAM­ABAD: Ra­pamycin and drugs that act like it have a lim­ited ef­fect against many can­cers be­cause their tu­mors are re­sis­tant to them. Now, the dis­cov­ery of a cell growth mech­a­nism could lead to new drugs that over­come this re­sis­tance in some can­cers.

The mech­a­nism in­volves a pre­vi­ously un­known pro­tein com­plex called mam­malian tar­get of ra­pamycin com­plex 3 (mTORC3).

Sci­en­tists at St. Jude Chil­dren's Re­search Hospi­tal in Mem­phis, TN, came across it by chance when they were do­ing an ex­per­i­ment.

Their study is the sub­ject of a pa­per that now fea­tures in the jour­nal Science Ad­vances.

"This new com­plex," ex­plains se­nior study au­thor Ger­ard C. Grosveld, who is the chair of the ge­net­ics depart­ment at the hospi­tal, "has not been on any­body's radar screen, even though mTOR com­plexes have been stud­ied for the last 25 years."

He and his team de­scribe the find­ing as a "par­a­digm shift" in our un­der­stand­ing of an im­por­tant cell growth mech­a­nism and de­clare that it of­fers a "novel tar­get for anti- cancer drug de­vel­op­ment."

The en­zyme mam­malian (or mech­a­nis­tic) tar­get of ra­pamycin (mTOR) plays a key role in the con­trol of cru­cial cell pro­cesses; it reg­u­lates growth and keeps it in a state of equi­lib­rium.

Ab­nor­mal ac­ti­va­tion of mTOR ap­pears as a fac­tor in an "in­creas­ing num­ber" of dis­eases; as well as cancer, these in­clude neu­rode­gen­er­a­tion, type, and obe­sity.

In cancer, ab­nor­mal mTOR ac­ti­va­tion pro­motes tu­mor growth. Ra­pamycin, as well as drugs that act like it — known as ra­palogs — are de­signed to stop this by block­ing mTOR.

Most ra­palogs, how­ever, have lim­ited ef­fect in cancer be­cause tu­mor cells are re­sis­tant to them.

Sci­en­tists had al­ready re­vealed that mTOR ex­erted its wide in­flu­ence from within two large pro­tein com­plexes: mTORC1 and


Grosveld and his team, how­ever, re­cently came across ev­i­dence to sug­gest that there might be a third mTOR pro­tein com­plex, and that a tran­scrip­tion fac­tor pro­tein called

ETV7 as­sem­bled it.

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