The Cancer Dormancy and Tumor Metastasis Institute (CDTMI), part of Montefiore Einstein Cancer Center, has selected two faculty research teams to receive its first pilot research awards. The winning teams will each receive a 1-year, $60,000 grant to advance their research that will later help gather data to apply for federal or private grants.
Both winning teams hope to better understand and combat residual disease—the chemotherapy-resistant cancer cells that remain in the body following treatment. These cells can reemerge later to cause metastases, which are responsible for the vast majority of cancer deaths.
The awardees are:
Neoadjuvant (pre-operative) chemotherapy is commonly used in cancer treatment aimed at shrinking tumors before they’re surgically removed. Most tumor cells succumb to this treatment, but a few may resist. Drs. LaFave and Karagiannis will use mouse models, cancer-cell organoids, and single-cell sequencing to study this surviving tumor-cell population in breast cancer, with the goal of broadening their observations to include other types cancers.
In earlier work, Drs. LaFave and Karagiannis identified a rare subpopulation of tumor cells that expressed high levels of the protein Tie2 after chemotherapy treatment. Tie2 is known to promote resistance and survival in normal cells, and the researchers will determine whether Tie2 also encourages certain breast-cancer cells to resist chemotherapy and continue to multiply. These studies may lead to novel treatments for targeting “chemoresistant” breast cancer cells and ultimately improving patient outcomes.
Dr. LaFave is assistant professor of cell biology and Dr. Karagiannis is assistant professor of microbiology & immunology.
Drs. Dhimolea and Gavathiotis recently developed clusters of cultured tumor cells, called organoids, that can be used to mimic treatments that lead to persistent cancer cells that emerge following chemotherapy. After analyzing post-treatment residual tumor cells in their tumor organoid models and in cancer patients, the researchers found that the cells survive by entering a therapy-induced dormant state. The dormancy prevents the cell-death mechanism called apoptosis from activating and killing the cancer cells by destroying their mitochondria.
Using the organoid model, the scientists will study the molecular mechanism that enables dormant tumor cells to evade cell death and will look for ways to restore apoptosis. More specifically, they will test whether combinations of investigational drugs can activate apoptosis, in both chemo-resistant cancer cells grown in organoids and in mouse models of cancer.
Dr. Dhimolea is assistant professor of molecular pharmacology and Dr. Gavathiotis is professor of biochemistry and of medicine.
Posted on: Wednesday, September 21, 2022