Combining Multiomics and Histological Assessment to Identify PDX Models of Invasive Lobular Carcinoma
Most breast cancers (~85%) are of no special histologic subtype (NST), and the most common special subtype is invasive lobular cancer (ILC). ILC accounts for 10-15% of all breast cancers, and there will be ~40,000 new cases in 2022 in the US alone. If considered an “independent” cancer type, ILC is the 6th most common cancer in women. The pathognomonic feature of ILC is loss of E-cadherin (CDH1). The resulting lack of adherens junctions causes the unique single-file growth pattern of discohesive ILC cells, which decreases the ability for detection by mammography, in turn resulting in late detection and hence larger tumors. Although ILCs show better prognostic factors than NST, patients with ILC have worse long-term outcome, which is not well understood. ILC has historically been understudied, which is in part due to lack of appropriate research models. For example, the Cancer Cell Line Encyclopedia (CCLE) contains 54 NST cell lines but only 2 ILC cell lines, and only a limited number of patient-derived xenograft (PDX) models are evident in the published literature. There is a critical need for additional in vitro and in vivo models to study ILC biology, as well as to test targeted therapies. ILC PDX and patient derived xenograft organoids (PDXO) are particularly valuable tools to enable target validation and assess drug treatment response.