Breast cancer is one of the most common malignancies affecting women with over 1.3 million new diagnoses and 500,000 deaths per year worldwide. It is a highly heterogeneous disease with widely varying prognosis and response to therapy: some women could be cured by surgery alone whereas others quickly succumb to the disease despite our most advanced medical treatment.
This is because, at the molecular level, each breast cancer is unique, harboring its own specific configuration of gene/genomic/epigenetic aberrations and gene expression changes. These alterations are thought to impinge upon an array of possible oncogene/tumor suppressor pathways, which in aggregate, allow the tumor cells to overcome built-in cellular defense mechanisms and, at the same time, enable new physiologic capabilities that define malignancy.
However, it is still far from understood how specific genetic alterations, patterns of mutations, and the resultant activation of particular pathways contribute to breast cancer diversity, tumor aggressivity, or to therapeutic sensitivity and resistance. Moreover, a major challenge in cancer research is how to capitalize on the aberrations which the tumor depends on for survival and convert these aberrations into molecular "Achilles’ heels" that can be targeted pharmacologically.
My research as well as the work of others has highlighted the role of the PTEN/PI3K/AKT pathway as a key promotor of tumorigenesis and as a target for therapeutic modulation. With a particular interest in this pathway, my research applies recent advances in genome-wide technologies to study breast cancer biology with the goal of translating our findings into new clinical applications. We are also investigating the clinical utility of monitoring circulating tumor DNA (ctDNA) in cancer patients. Specifically, we aim to:
- Discover the patterns of gene mutation, genomic aberrations, and gene expression changes within human breast tumors
- Ascertain the utility of circulating tumor DNA by “liquid biopsy” as a robust cancer biomarker
- Understand the relationship of these aberration patterns to clinicopathological parameters such as patient survival
- Study the functional significance of identified aberrations in model systems
- Utilize this "-omic" information to design and test rational combinatorial therapeutics that target more specifically the actual cancer mutations and pathways that are active in a individual patient's tumor
- Validate and translate to the clinic new biomarker diagnostic assays for selection of optimal therapy and monitoring residual disease and response to therapy
- Develop core bioresources and technology/bioinformatics infrastructure
Our research is facilitated by close cooperation with fellow research units of the Canceromics Branch and Division of Oncology and Pathology, collaborations internationally, partnership with clinical oncologists, surgeons, and pathologists, and participation as one of the principal executors of the Sweden Canceromics Analysis Network - Breast (SCAN-B) Initiative.
- Aug 25: Swedish National TV4 broadcast of interview with Lao Saal (3 minute clip, English with Swedish subtitles).
- Aug 15: Paper on PTEN and NEDD4 in breast cancer published in Pathology & Oncology Research.
- Jun 29: Lao presents at the Personalised Medicine conference, Embassy of Sweden in Tokyo, Japan.
- Jun 11: Lao awarded major grants from VINNOVA SWElife and Berta Kamprad Foundation.
- May 18: Circulating tumor DNA paper published in EMBO Molecular Medicine (cover article). Notable mentions in other media: GenomeWeb, ScienceDaily, RD Magazine, Läkartidningen, Forskning.se, Medicinsk Access, and Sydsvenskan, among others.
- Feb 2: SCAN-B paper published in Genome Medicine.