RESUMO
Background: Chordomas are rare neuraxial tumors arising from remnants of primitive notochord. They are generally slow-growing malignant neoplasms. Only four adult cases of multicentric chordomas have been reported, all with aggressive and rapid growth. Here, we present an unusual case of indolent multicentric chordomas involving cervical and thoracic spine, sacrum, and calvarium. Case Description: A 60-year-old male was found to have multiple lesions throughout his neuroaxis incidentally on workup for colitis. A needle biopsy documented the diagnosis of chordoma. This has been followed for more than 4 years with no progression. Conclusion: We present the first reported case of indolent multicentric chordomas. Due to the extreme rarity of indolent multicentric chordomas, close follow-up is needed and recommended.
RESUMO
Hormonal therapy targeting androgen receptor (AR) is initially effective to treat prostate cancer (PCa), but it eventually fails. It has been hypothesized that cellular heterogeneity of PCa, consisting of AR+ luminal tumor cells and AR- neuroendocrine (NE) tumor cells, may contribute to therapy failure. Here, we describe the successful purification of NE cells from primary fresh human prostate adenocarcinoma based on the cell surface receptor C-X-C motif chemokine receptor 2 (CXCR2). Functional studies revealed CXCR2 to be a driver of the NE phenotype, including loss of AR expression, lineage plasticity, and resistance to hormonal therapy. CXCR2-driven NE cells were critical for the tumor microenvironment by providing a survival niche for the AR+ luminal cells. We demonstrate that the combination of CXCR2 inhibition and AR targeting is an effective treatment strategy in mouse xenograft models. Such a strategy has the potential to overcome therapy resistance caused by tumor cell heterogeneity.