Scientists are currently developing a predictive method to evaluate how triple-negative breast cancer (TNBC) responds to chemotherapy.

This innovative approach is poised to become an invaluable resource for physicians, as it will empower them to customize treatment plans for each patient, significantly improving the chances of successful outcomes. Study findings were published in Cancer Research Communications.

"Multiple research innovations in cancer diagnostics are on display in this work," said co-corresponding author Dr. Matthew Ellis, member of the Lester and Sue Smith Breast Center and the Dan L Duncan Comprehensive Cancer at Baylor and also senior vice president of early oncology and oncology R&D at AstraZeneca.

Investigating the Kinase Inhibitor Pulldown Assay (KIPA) in Triple Negative Breast Cancer

Researchers used KIPA to identify targetable proteins for tumor growth control in 43 frozen tumor biopsies.

"Our initial goal was to find new ways to control TNBC growth, specifically by identifying and then inhibiting enzymes called kinases produced by the tumor to assist in its growth," said co-corresponding author Dr. Meenakshi Anurag, assistant professor of medicine at the Lester and Sue Smith Breast Center at Baylor. "Although our search for such kinases did not produce valuable candidates, it unexpectedly revealed an opportunity to improve the success of chemotherapy."

KIPA operates by coating minute beads with specific kinase inhibitors, subsequently lysing the cells in the biopsy samples, and combining them with the coated beads.

Researchers isolate kinases by selectively binding to their corresponding inhibitors, separating them from other cellular components. Beads are cleaned and kinases identified using mass spectrometry for individual identification.

Purine-Binding Proteins: An encouraging Indicator for Anticipating Chemotherapy Sensitivity

"This approach did not reveal kinases we could potentially target to control these tumors' growth; however, the assay captured seven non-kinase proteins, specifically purine-binding proteins, that were enriched in tumors that completely responded to treatment," said first author Junkai Wang, a graduate student working in the Ellis lab. "Further analyses showed that this seven-purine-binding protein signature predicted chemotherapy sensitivity and favorable clinical outcomes."

"Although originally KIPA was developed for the accurate quantification of druggable kinases, this paper demonstrates that its clinical utility extends beyond kinase quantification. With more clinical sample analysis, there is a great possibility that we will be able to identify additional signatures for many therapeutic strategies," said co-corresponding author Dr. Beom-Jun Kim, member of the Lester and Sue Smith Breast Center and the Dan L Duncan Comprehensive Cancer at Baylor and also associate director of diagnostic proteomics at AstraZeneca.

"We are excited about these findings, which we have validated in multiple TNBC cohorts," Anurag said. "In addition, KIPA offers other advantages: it produces results in a time-efficient manner and requires a much smaller tumor sample than other methods."