Researchers have discovered a new combination therapy to treat drug resistant breast cancer.

About 15-20% of breast cancer diagnoses are an HER2-positive subtype. Traditional therapy only works successfully in one-third of patients with this type of cancer, and even then resistance eventually develops in most of these patients.

This is a common issue faced by treatments that target kinases-specific proteins which are essential to cellular activity. HER2 is the primary kinase responsible for tumor growth in this form of cancer.

The combination therapy involves the commonly used drug lapatinib and a new experimental drug called a BET bromodomain inhibitor.

BET bromodomain inhibitors are used to disrupt the expression of certain genes. These inhibitors have been demonstrated to prevent the development of resistance to lapatinib in cell lines of human HER2 positive breast cancer.

The new combination treatment is currently being tested in difference moue models of breast cancer. The goal is to create a new kind of therapy that could help oncologists make the response to treatment more durable and lasting for breast cancer patients.

Lapatinib works by blocking HER2, unforuntately, cancer cells are able to use other kinases to find a way around the blockage. Therefore the cells become resistant to lapatinib.

Due to toxicity concerns, it is not possible to inhibit all of the kinases that potentially help cancer cells compensate in the face of an HER2 inhibitor. The more drugs a patient uses, the more toxic it is and the lower the dose people are able to tolerate.

When BET bromodomain inhibitor was combined with lapatinib, not only was the HER2 kinase blocked, but the massive kinase response which was previously observed did not occur. This ultimately led to the deaths of the cancer cells. Essentially this treatment makes the activity of lapatinib durable.

Gerry Oginski
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