Publications by authors named "I Masilionis"
As cancers progress, they become increasingly aggressive-metastatic tumours are less responsive to first-line therapies than primary tumours, they acquire resistance to successive therapies and eventually cause death. Mutations are largely conserved between primary and metastatic tumours from the same patients, suggesting that non-genetic phenotypic plasticity has a major role in cancer progression and therapy resistance. However, we lack an understanding of metastatic cell states and the mechanisms by which they transition.
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- Recent advancements in genetic manipulation have made it possible to create specific deletions in mitochondrial DNA (mtDNA) in human cells, which can help study diseases linked to these genetic changes.
- A method involving co-expression of end-joining machinery and targeted endonucleases was developed, showcasing effectiveness by generating clonal cell lines with a significant mtDNA deletion and varying levels of heteroplasmy.
- Research showed that when mtDNA deletion reached around 75%, it led to severe cellular dysfunction and identified distinct nuclear gene expression changes in response to mtDNA deletions, suggesting insights for potential therapies.
Article Synopsis
- Targeting cell surface molecules with therapies like radioligands and antibodies has been effective in treating various cancers, but the impact of lineage plasticity on these markers is still poorly understood.
- A specific example of lineage plasticity is the transformation of prostate adenocarcinoma to neuroendocrine prostate cancer, which poses significant treatment challenges and worsens patient survival rates.
- Research using advanced single-cell analyses and large tumor sample studies revealed significant phenotypic variability and shared gene-regulatory networks between NEPC and small cell lung cancer, raising concerns about the effectiveness of current therapies while suggesting potential for better patient selection in clinical trials.
Targeting cell surface molecules using radioligand and antibody-based therapies has yielded considerable success across cancers. However, it remains unclear how the expression of putative lineage markers, particularly cell surface molecules, varies in the process of lineage plasticity, wherein tumor cells alter their identity and acquire new oncogenic properties. A notable example of lineage plasticity is the transformation of prostate adenocarcinoma (PRAD) to neuroendocrine prostate cancer (NEPC)--a growing resistance mechanism that results in the loss of responsiveness to androgen blockade and portends dismal patient survival.
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