Identification of Molecular Markers Associated with Prostate Cancer Subtypes: An Integrative Bioinformatics Approach DOI Open Access
Ilaria Granata, Paola Barboro

Published: Nov. 16, 2023

Prostate cancer (PCa) is characterised by androgen-dependency. Unfortunately, under anti-androgen treatment pressure, castration-resistant prostate (CRPC) emerges, heterogeneous cell populations that, over time, lead to the development of different androgen-dependent or -independent phenotypes. Despite important advances in therapeutic strategies, CRPC remains incurable. Context-specific essential genes represent valuable candidates for targeted anti-cancer therapies. Through investigation gene and protein annotations integration several published transcriptomic data, we identified two consensus lists stratify PCa patients' risk discriminate phenotypes based on androgen receptor activity. ROC Kaplan-Meier survival analyses were used set validation independent datasets. We further evaluated these their association with dependency. The deregulated expression PCa-related was associated overall disease-specific survival, metastasis and/or high recurrence risk, while CRPC-related clearly discriminated between adeno neuroendocrine Some showed context-specific essentiality. candidate drugs through a computational repositioning approach targeting treating lethal variants PCa. This work provides proof-of-concept use an integrative identify biomarkers involved progression pathogenesis within goal precision medicine.

Language: Английский

A novel role for Neurog2 in MYCN driven neuroendocrine plasticity of prostate cancer DOI Creative Commons
Franco J. Vizeacoumar,

Prachi Walke,

Jared D.W. Price

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

Abstract Neuroendocrine prostate cancer (NEPC) presents a formidable clinical challenge owing to its aggressive progression and resistance conventional therapies. A key driver of NEPC is the overexpression MYCN, well-established oncogene associated with neuroendocrine tumors. However, efforts directly inhibit N-Myc protein encoded by this gene have resulted in limited success, thereby hindering therapeutic advancements. To overcome obstacle, we conducted unbiased genome-wide screening using isogenic cell lines identify synthetic vulnerabilities MYCN. Among identified candidates, NEUROG2 emerged as significant candidate. Neurog2 proneural transcription factor (PTF) known for role developmental processes trans-differentiation adult cells. Our findings demonstrate that depletion does not affect non-malignant cells, but significantly suppresses growth MYCN-overexpressing cells tumors orthotopic models. Furthermore, our observations indicate Neurog2-mediated regulation PTFs can facilitate development. Thus, targeting holds promise an effective strategy NEPC.

Language: Английский

Citations

0
The molecular determinants of phenotypic plasticity in homeostasis and neoplasia DOI Creative Commons

Bradley Balk,

David W. Goodrich

Published: Dec. 13, 2024

Phenotypic plasticity, the capacity of cells to transition between distinct phenotypic and lineage states over time, is a genetically epigenetically encoded trait essential for normal development adult tissue homeostasis. In cancer, plasticity programs can be deployed aberrantly enable disease progression acquired therapeutic resistance. Cancer current barrier achieving cures advanced cancers using available molecularly targeted therapies. This review summarizes complex interconnected molecular pathways implicated in both context homeostasis cancer. Molecular convergent these contexts are highlighted while enabling distinguished from those that specify phenotype already plastic cells. Key unresolved questions field discussed along with emerging technologies may used help answer them.

Language: Английский

Citations

0
Identification of Molecular Markers Associated with Prostate Cancer Subtypes: An Integrative Bioinformatics Approach DOI Open Access
Ilaria Granata, Paola Barboro

Published: Nov. 16, 2023

Prostate cancer (PCa) is characterised by androgen-dependency. Unfortunately, under anti-androgen treatment pressure, castration-resistant prostate (CRPC) emerges, heterogeneous cell populations that, over time, lead to the development of different androgen-dependent or -independent phenotypes. Despite important advances in therapeutic strategies, CRPC remains incurable. Context-specific essential genes represent valuable candidates for targeted anti-cancer therapies. Through investigation gene and protein annotations integration several published transcriptomic data, we identified two consensus lists stratify PCa patients' risk discriminate phenotypes based on androgen receptor activity. ROC Kaplan-Meier survival analyses were used set validation independent datasets. We further evaluated these their association with dependency. The deregulated expression PCa-related was associated overall disease-specific survival, metastasis and/or high recurrence risk, while CRPC-related clearly discriminated between adeno neuroendocrine Some showed context-specific essentiality. candidate drugs through a computational repositioning approach targeting treating lethal variants PCa. This work provides proof-of-concept use an integrative identify biomarkers involved progression pathogenesis within goal precision medicine.

Language: Английский

Citations

1