A new study sheds light on how a drug called a cell-cycle kinase inhibitor may be used most effectively to treat patients with ovarian cancer. About 20% of patients with ovarian cancer have high expression of a cell-cycle driver called cyclin E1 in their tumor cells. Because cyclin E1 needs the kinase CDK2 to activate gene expression for cell cycling, CDK2 inhibitors are very effective against cyclin E1–high cancer cells in culture and in mouse models. However, other CDKs – namely CDK4 and CDK6 – can compensate for CDK2’s loss and can fuel drug-resistant growth, just as CDK2 is known to drive resistance to CDK4/6 inhibitors in breast cancer. Here, Chance Sine and colleagues explored this relationship in ovarian cancer cells. They found that cyclin E1–high tumors that are sensitive to CDK2 inhibitors have an abundance of a protein that blocks the compensatory CDK4/6 signal. The authors analyzed cell cycling and protein dynamics in hundreds of thousands of single ovarian cancer cells treated with CDK2 inhibitors. This revealed that cells with high abundance of a protein called p16 were more potently and durably sensitive to the drug and had decreased activity of CDK4/6. Knocking down the expression of p16 enabled a faster emergence of resistance, suggesting that p16 is a natural brake on the resistance mechanism. Previous work has shown that p16’s normal function is to suppress uncontrolled cell proliferation by physically inhibiting the activity of CDK4/6. p16 is absent in many cancers through mutation or deletion, but is abundant in some other tumors, particularly those with underlying infection with the HPV virus (as in some ovarian cancers). In over 200 patient samples of ovarian cancers, nearly a fifth were abundant in p16 as well as in cyclin-E1, and p16 expression was actually a better predictor of shorter survival in patients. CDK2 inhibitors, including those used here, are currently in early-phase clinical trials for patients with cyclin E1–high tumors. To make the most of the drug’s potential for patients, “p16 may be a useful biomarker for identifying the patients most likely to benefit from [CDK2 inhibition],” Sine et al. write.

Researchers at the LSU LCMC Health Cancer Center have published groundbreaking findings in NPJ Breast Cancer that sheds new light on triple-negative breast cancer (TNBC), one of the most aggressive forms of breast cancer.

The drug dexamethasone supplements cancer treatments to alleviate side effects of chemotherapy such as nausea or inflammation. Researchers at the University of Basel, Switzerland, have now discovered that it also fights metastases in certain types of breast cancer.

For Dena and Richard, UCLA Health is not just a medical team, it’s become family. “Dr. Chi and the whole team are one in a million,” said Dena. “They helped save both of our lives.”