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Lisa Prior, MB, BCh, BAO, MRCPI

Fellow, Medical Oncology 
Strategic Academic Research MD Research Scholar
Royal College of Surgeons of Ireland 
Conquer Cancer, the ASCO Foundation

Current Research

Goal: Investigating the use of P13K inhibitor combinations to improve treatment outcomes for patients with HER2-positive breast cancer.

Impact: Metastatic breast cancers that produce high levels of HER2 protein are considered aggressive. Treatments that block the HER2 protein have improved the outcomes for patients but most of these cancers become resistant to treatment. This occurs due to the activation of the “PI3K pathway” due to a mutation in the DNA of HER2-positive cancer cells. Dr. Prior is conducting studies to assess the efficacy of using a P13K inhibitor, Copanlisib, in combination with other HER2 blocking treatments to treat HER2-positive metastatic breast cancer patients. 

What’s next: She and her team will collect blood samples from patients regularly during treatment to check for cancer cells and cancer cell DNA (liquid biopsy) to determine if changes in their levels correlate with a response to treatment. 

Approximately, 20 percent of metastatic breast cancers produce high levels of HER2 protein and are considered aggressive. Treatments that block the HER2 protein have improved the outcomes for patients but most of these cancers eventually grow and become resistant to treatment. Dr. Prior’s research will determine the efficacy of using a P13K inhibitor, Copanlisib, in combination therapy to treat HER2-positive metastatic breast cancer patients and improve outcomes for these patients.

Full Research Summary

Research Area: Investigating the use of P13K inhibitor combinations to improve treatment outcomes for patients with HER2-POSTIVE breast cancer.

Impact: Approximately, 20 percent of metastatic breast cancers produce high levels of HER2 protein and are considered aggressive. Treatments that block the HER2 protein, such as Trastuzumab (Herceptin), have improved the outcomes of these patients–they live longer and with improved quality of life. However, most of these cancers eventually grow and become resistant to treatment. One way in which this occurs is through activation of the PI3K pathway due to a mutation in the PIK3CA gene. Blocking this pathway with a PI3K inhibitor may make HER2-positive cancer cells more sensitive to HER2 blocking drugs as indicated by previous studies. Dr. Prior is conducting studies to assess the efficacy of using a P13K inhibitor, Copanlisib, in combination with other HER2 blocking treatments to treat HER2-positive metastatic breast cancer patients. She hopes the results of these investigations will help to inform treatment options for patients and personalize their care. 

Current Research: As part of her Conquer Cancer study, supported by BCRF, Dr. Prior is assessing the safety of the P13K inhibitor, Copanlisib, in combination with Trastuzumab‐Emtansine (T‐DM1, a standard second line HER2 blocking therapy) in patients with metastatic HER2-positive breast cancer whose disease has grown after initial treatment. In preliminary studies, Dr. Prior has utilized HER2-positive cancer cells that had become resistant to HER2-directed therapies. When treated with the combination of Copanlisib and a HER2-directed treatment, she found that cell growth was significantly reduced. She is now testing three doses of Copanlisib to determine the safest and best tolerated dose as well as assessing response rates, optimal timing of treatment and survival time after treatment initiation. She and her team will collect blood samples from patients regularly during treatment to check for circulating tumor cells and circulating tumor DNA (liquid biopsy) to determine if changes in their levels correlate with a response to treatment. In addition, sequencing will be performed on patient tumor biopsies before and after treatment to examine treatment induced genetic changes. They hope to identify gene patterns that may predict which cancers will respond to treatment versus those that will be resistant. 

Biography

Lisa Prior MB, BCh, BAO, MRCPI is a medical oncology fellow and StAR (Strategic Academic Research) scholar at the Royal College of Surgeons of Ireland (RCSI). She obtained her undergraduate degree (MB BCh BAO) from University College Dublin (UCD), completed her internal medicine training in Ireland and obtained membership of the Royal College of Physicians of Ireland (RCPI). Her research interests have included pregnancy associated breast cancer and cardiovascular disease in breast cancer patients receiving adjuvant therapy. Dr. Prior hopes to dedicate her career as a clinician‐scientist to identifying mechanisms of resistance to breast cancer therapies and strategies to overcome them.

BCRF Investigator Since

2020

Area(s) of Focus