Exosomal Perp emission in response to targeted breast cancer therapy: diagnostic implications

Dr Kirill Rosen?s goal is to develop a new method of testing and predicting the effectiveness of an anticancer drug called lapatinib (Tykerb). This drug slows down breast cancer in some but not all patients. Whether the drug will work in each person cannot be predicted. Whether this drug is working is now tested using imaging methods that can be costly and are not always available. Tumour cells secrete tiny particles into the blood. Dr Rosen and his team found that lapatinib forces lapatinib susceptible but not lapatinib resistant breast cancer cells grown on a dish to produce particles carrying a protein called Perp. They will test whether Perp levels in particles in the blood of mice and people with breast tumours who are treated with lapatinib reflect whether the drug is working. Many breast tumours overproduce an cancer-causing protein called HER2. HER2 dependent signals alter levels of various proteins in cells. The researchers found recently that to turn normal breast cells into tumour cells, HER2 needs to lower cellular levels of the cell death inducing protein Perp. They observed that the effect of HER2 on Perp can be blocked by lapatinib, an HER2 inhibitor. Lapatinib can kill breast cancer cells and is used for breast cancer treatment. Not all people with breast cancer benefit from lapatinib, because in some cases breast cancers cannot be killed by this drug for poorly understood reasons. Whether or not someone with breast cancer will benefit from lapatinib cannot be predicted. Finding out whether the drug is working in the case of each individual currently involves methods that can be expensive and are not always accessible (e.g. magnetic resonance imaging [MRI]). Researchers found that lapatinib increases Perp levels in tiny particles produced by lapatinib susceptible breast cancer cells but not in those emitted by lapatinib resistant breast cancer cells when grown on a dish. Researchers will inject mice with lapatinib resistant or lapatinib susceptible breast cancer cells into the mammary tissue (where breast tumours originate) or in the brain (an organ to which many breast cancers spread). They will then let the tumours form, treat the mice with lapatinib and monitor how the tumours shrink. They will measure Perp levels in the particles present in the mouse blood. If Perp levels in these particles reflect tumour sensitivity to lapatinib, this will indicate that such levels can be measured to determine whether the drug is working. If Perp levels increase in the particles released from lapatinib-susceptible cancer cells before the tumours shrink in response to the drug, this will indicate that Perp levels in such particles can be used for predicting whether the drug will work. Finally, researchers will test whether Perp accumulates in the particles in the blood of people with breast cancer during lapatinib treatment and whether this accumulation is linked with survival. This work could give rise to a new way to predict and measure the effectiveness of lapatinib against breast cancer. If the use of this approach allows doctors to predict whether the drug will work in a particular person with breast cancer, this could help them decide whether this person should be receiving lapatinib. Furthermore, imaging tests that are presently used for determining the effectiveness of lapatinib can be costly and are not always accessible. If the method developed by Dr Rosen?s group can be used for determining whether the drug is working, this could reduce the frequency with which people with breast cancer need to undergo these imaging tests.