Molecular Pump That Spits Out Cancer Drugs

MRP1 Molecular pump. Image credits: SimBac
CANCER-A HARD NUT TO CRACK?

Cancer research started several decades ago. Even after investing billions in cancer research, we still have more questions than answers. However, the most frequent question asked is why scientists’ haven’t cured cancer yet?

If we can go to mars, why can’t we cure cancer? If we can harness the energy of an atom, why can’t we cure cancer?

Scientists probably can say this: Because it’s hard. It’s very, very hard. It’s harder than building the nuclear bomb and probably harder than going to mars. All of these were, of course, also very, very hard too, but cancer is a harder nut to crack still. Cancer as a whole is, perhaps thousands, of diseases.

Each type of cancer can be many, even dozens, of different diseases in itself. Each tumor has different prints.  More so, it is constantly evolving, both in response to the environment in which the cancer cells grow and to treatments that are thrown at them.

In connection to this, a recent structural study published in Cell, reveals the workings of a molecular pump that ejects cancer drugs.  Researchers at the Rockefeller University, have revealed that cancer cells literally ‘spit’ out cancer drugs that are supposed to kill them.

They do so by employing ATP-binding cassette (ABC) transporters. These transporters or ‘molecular pumps’ eject numerous anticancer agents, as well as other drugs. However, scientists were looking for years, how can cancer cells recognize and remove such an impressive variety of substances.

Jue Chen, professor and head of the laboratory of membrane biology and biophysics at the Rockefeller University found an answer. Using advanced cryo-electron microscopes, she along with researcher Zachary Johnson, elucidated the structure of MRP1 (Multidrug resistance-associated protein 1), a common ABC transporter.

MECHANISM OF THE MOLECULAR PUMP

The MRP1 has a structure similar to pincers. However, the central pocket structure is versatile and this allows it to clasp its cargo. Formed by the two flexible sides, it accommodates cargo of varying size.

Many of the substances that bind to MRP1 match with the pocket’s two-part print; but those that don’t, as it turns out are coupled to a filler molecule from inside the cell. Now that’s evolution!!!

Once in the pocket, the cargo connects the two halves of MRP1, pulling them together, as if pinching the pincers. This leads to enough force being applied which releases the cargo outside the cell.

Molecular pump structure
On the way out. Image source: Cell Press
IS THIS THE BLUEPRINT FOR SUCCESS?

Chen says “by examining how this molecular pump works and binds to its cargo, we can have an answer to the chemoresistance of cancer cells.

Johnson hopes that these structures could serve as blueprints for designing chemotherapy drugs the pumps don’t identify, or inhibitors that block them. These could guide the development of better treatment for cancers.

Now we know the mechanism of chemoresistance of cancer cells. Maybe we will find a cure for cancer. After all, never before have we had the advancement that we have now to probe the biology of cancer.

Hope dies last.

 

Read Also:

These Cancer Drugs Will Dominate The Medical Landscape In 2022

Source Cell press Rockefeller University

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