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Overview

Sempere Laboratory

microRNA Diagnostics and Therapeutics

sempere-lab-logoThe Sempere Laboratory pursues complementary lines of translational research to explain the etiological role of microRNAs and unravel microRNA regulatory networks during carcinogenesis. The lab investigates these questions in clinical samples and pre-clinical models of breast cancer and pancreatic cancer. Led by Dr. Lorenzo Sempere, the laboratory has several active projects in the areas of cancer biology and tumor microenvironment with a translational focus on molecular and cellular heterogeneity and its clinical implications for improving diagnostic applications and therapeutic strategies.

WHY IS IT IMPORTANT?

Breast cancer is the most prevalent cancer type and second leading cause of cancer-related death in women in the U.S. Breast cancer is not a single disease but rather an array of distinct cellular and molecular diseases that arise from breast epithelial cells. Major breast cancer subtypes have been identified that differ in respect to treatment response and clinical outcomes. While breast cancer patients have an overall good survival rate of more than 70 percent, the large number of afflicted patients poses an important public health problem that requires better management tools for personalized care and treatment options.

  • Improved diagnostics, such as the incorporation of microRNA biomarkers, would provide a better understanding of tumor biology and would help avoid unneeded overtreatment of some patients (e.g., subsets of early stage hormone-responsive tumors).
  • In other instances, such as aggressive triple-negative breast cancer and/or advanced stage cases, better tumor characterization could lead to new drug development and treatment strategies, including microRNA-based compounds.

Pancreatic cancer is the fourth leading cause of cancer-related death in both men and women in the U.S. Pancreatic cancer has a disproportionally high mortality rate and fewer than 10 percent of patients survive more than five years after diagnosis. Late presentation of cancer symptoms (advanced stage when diagnosed) and intrinsically aggressive characteristic of pancreatic ductal adenocarcinoma (major histological subtype) are great challenges to overcome. Fewer diagnostic and treatment options exist for pancreatic cancer compared to breast cancer and other cancer types. Thus, unmet clinical needs from pancreatic cancer are vast and different from other cancer types.

  • Focused areas of urgent need include early disease detection tools and differential diagnosis of precursor lesions as well as new therapeutic intervention strategies. microRNAs offer innovative opportunities to tackle these challenges.
  • As treatment approaches that target cancer cells have achieved little improvement in the last decade, combination strategies that also target the stroma and boost immune system responses could improve treatment responses by interfering with cancer cell growth and the tumor microenvironment. Candidate microRNAs exist that could be targeted to affect cancer cell, stromal cell and/or immune cell biology.
ABOUT MICRORNA

microRNAs are evolutionary conserved short non-coding regulatory RNAs. The discovery of microRNAs has revolutionized the fields of biological and biomedical sciences and has led to important conceptual and technological innovations. Additionally, microRNAs are pivotal players in human diseases, including cancer. Their unique chemical and biological characteristics make them attractive candidates for diagnostic and therapeutic applications in cancer since expression and function of microRNAs are tightly linked. microRNA can regulate and modulate mRNA expression levels in of hundreds of target genes, some of which are components of the same signaling pathway and/or biological process. Accordingly, functional modulation of a single microRNA can concertedly affect multiple target mRNAs (i.e., one drug, multiple hits), unlike small interfering (siRNA)-, antibody- or small molecule inhibitor-based therapies (i.e., one drug, one hit). Therefore, the utility of key microRNAs as biomarkers for interrogating tumor biology could also be exploited as pharmacological targets.