YB-1 induction of PIK3CA mediates herceptin resistance in Breast Cancer patients

Breast cancer accounts for more than 30 per cent of all new cancer cases in Canada. One in nine women will be diagnosed with breast cancer in their lifetime, while one in 27 will die of the disease. This translates to 23,000 new diagnoses and 5,300 deaths in Canada every year. An aggressive form of breast cancer is called the Her-2 subtype. These tumours produce a protein called Her-2, which helps the cells grow uncontrollably. The drug Herceptin acts against the Her-2 protein. While this drug is effective, there are limitations to Herceptin’s usefulness since many patients develop resistance to the drug. Recent research has uncovered a protein called Y-box binding protein-1 (YB-1), which is expressed (produced) at high levels in the Her-2 subtype of breast cancer. While the YB-1 protein is not found in normal cells, it is found in 66.4 per cent of Her-2 subtype breast cancers. This makes YB-1 an attractive target for treatment, as inhibiting it will not affect normal cells. The protein promotes tumour growth by altering the levels of other tumour-enhancing proteins, such as PI3K. Arezoo Astanehe is investigating whether the increase in PI3K by YB-1 is one reason that cells become resistant to the effects of Herceptin. She hypothesizes that by inhibiting YB-1 and PI3K expression, Her-2 cancer cells would remain sensitive to Herceptin. Astanehe’s findings could identify new drug targets to help prevent Herceptin resistance and increase long-term survival of women with this aggressive and deadly form of breast cancer.