快猫短视频

CANCER patients and people with osteoporosis could get relief from two new
ways of targeting bone-destroying cells. One group of US researchers has found a
drug that can dramatically reduce the pain of bone metastases, and another has
identified a target for drugs that could protect bone as well as stopping the
spread of cancer cells.

Because bone has to withstand severe pressures, the body constantly renews
its skeleton by breaking bone down and building it back up. Diseases such as
osteoporosis or bone cancer, however, disrupt the careful balance between
bone-destroying cells called osteoclasts and bone-building osteoblasts. Now,
Patrick Mantyh and his colleagues at the University of Minnesota in Minneapolis
have shown that hyperactive osteoclasts create the pain associated with bone
metastases, and that they can prevent it with a drug called osteoprotegerin
(OPG).

Mantyh鈥檚 team injected cancer cells into mouse femurs, which stimulated
excessive osteoclast activity, as would also happen in people. When X-rays began
to show bone degradation, Mantyh treated some of his mice with OPG, which
inhibits osteoclasts by intercepting a chemical message that tells the cells to
break down bone.

The mice that got OPG reacted normally, and the drug almost completely
prevented bone damage associated with cancer. But the mice that went without OPG
did have damage and would flinch when researchers touched their legs. Mantyh
thinks OPG, which is being developed as an osteoporosis drug by the company
Amgen in Thousand Oaks, California, has great potential for treating pain and
damage from bone metastases. 鈥淚 would be very surprised if it is not pushed
ahead as rapidly as possible for this application,鈥� says Mantyh. Current drugs
can鈥檛 suppress the pain caused by bone cancer.

However, while OPG doesn鈥檛 seem to enhance tumour growth, it doesn鈥檛 stop it
either. So Keith Hruska and his colleagues at Washington University School of
Medicine in St Louis are looking for a way of inhibiting osteoclasts and bone
metastases at the same time. They have been studying how osteoclasts create
foot-like extensions called podosomes that let them 鈥渨alk鈥� through bone. Certain
cancer cells also move via podosomes.

Previous work by Hruska鈥檚 group with knockout mice suggested that osteoclasts
needed a protein called gelsolin to make podosomes. Mice without this protein
had thicker bones, but they suffered from minor abnormalities in their blood,
immune system and skin. So the researchers looked for another drug target and
found that chicken osteoclasts couldn鈥檛 form podosomes without a rare form of a
certain enzyme, triggered by another protein called Rho. What鈥檚 more, molecules
that inhibit both the enzyme and Rho can reduce bone breakdown by osteoclasts,
the researchers found.

Hruska鈥檚 team are testing these molecules in mice with osteoporosis. But they
want to kill two birds with one stone by seeing if the drugs can also inhibit
the podosomes that help cancer cells get around. 鈥淲e think that there鈥檚 direct
potential in treating cancer here,鈥� Hruska says.