to reduce immune- suppression in triple negative breast cancer Questions that may arise in your mind: ➢ What is triple negative breast cancer? ➢ Why are you studying triple negative breast cancer? ➢ Why is immune-suppression a problem in triple negative breast cancer? ➢ What data suggests that p38 is the target to go after? ➢ What does your data show? ➢ What does this mean for the patients? Defining the question Developing the hypothesis Results and conclusion Overall Impact
the question- Background Triple Negative Breast Cancer (TNBC) has low expression of Estrogen receptor (ER-), Progesterone receptor (PR-) and Human epidermal growth factor receptor 2 (HER2-). -10 10 30 50 % survival 5-year Survival rate – Distant Metastasis Luminal A Luminal B HER2+ TNBC TNBC Luminal A Luminal B HER2+ https://seer.cancer.gov/statfacts/html/breast.html Major Need: to develop an effective treatment approach for TNBC.
ICI monotherapy remain poor. One of the major reasons for failure of ICI is due to immune-suppressive Tumor Microenvironment (TME). • Surgery • Radiation therapy • Chemotherapy Problems • Relapse and Resistance • Significant toxicity Response rates to ICI monotherapy Melanoma 40-50% Lung cancer 30-40% TNBC 10-15% Esteva F.P. et al, 2019 Vikas P., et al, Can Mgt Res, 2018 Emerging approach: Immune checkpoint inhibitors (ICI) • αPD-1 • αPD-L1
suppressive cells Create your illustrations using https://www.biorender.com/ State the gap in knowledge: There are currently no clinically approved agents to target immune suppressive cells. There is a need to develop therapies to target immune suppressive cells
of p38 MAP kinase in the tumor cells leads to generation of immune- suppressive microenvironment. Therefore, we hypothesize that blocking p38 will reduce immune suppression and enhance response to ICI therapy. p38