Molecular and Functional Links between Neurodevelopmental Processes and Treatment-Induced Neuroendocrine Plasticity in Prostate Cancer Progression DOI Open Access
Roosa Kaarijärvi, Heidi Kaljunen, Kirsi Ketola

et al.

Cancers, Journal Year: 2021, Volume and Issue: 13(4), P. 692 - 692

Published: Feb. 9, 2021

Neuroendocrine plasticity and treatment-induced neuroendocrine phenotypes have recently been proposed as important resistance mechanisms underlying prostate cancer progression. Treatment-induced (t-NEPC) is highly aggressive subtype of castration-resistant which develops for one fifth patients under prolonged androgen deprivation. In recent years, understanding molecular features phenotypic changes in has grown. However, there are still fundamental questions to be answered this emerging research field, example, why how do the treatment-resistant cells acquire neuron-like phenotype. The advantages change role tumor microenvironment controlling cellular emergence forms mostly unknown. Here, we discuss functional links between neurodevelopmental processes progression treatment resistance. We provide an overview neurite-like whether reported t-NEPC pathways proteins relate like neurogenesis axonogenesis during development also novel therapeutic targets modulating plasticity.

Language: Английский

Complexities of Prostate Cancer DOI Open Access
Sobia Wasim, Sang‐Yoon Lee, Jaehong Kim

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(22), P. 14257 - 14257

Published: Nov. 17, 2022

Prostate cancer has a long disease history and wide variety uncertainty in individual patients’ clinical progress. In recent years, we have seen revolutionary advance both prostate patient care the research field. The power of deep sequencing provided cistromic transcriptomic knowledge that not discovered before. Our understanding biology, from bedside molecular imaging techniques, also been greatly advanced. It is important our current theragnostic schemes, including diagnostic modalities, therapeutic responses, drugs available to target non-AR signaling should be improved. This review article discusses progress biology advances strategies.

Language: Английский

Citations

86
Biological determinants of PSMA expression, regulation and heterogeneity in prostate cancer DOI
Martin Bakht, Himisha Beltran

Nature Reviews Urology, Journal Year: 2024, Volume and Issue: unknown

Published: July 8, 2024

Language: Английский

Citations

16
The treatment landscape of metastatic prostate cancer DOI Creative Commons
Yasutaka Yamada, Himisha Beltran

Cancer Letters, Journal Year: 2021, Volume and Issue: 519, P. 20 - 29

Published: June 18, 2021

Language: Английский

Citations

92
Androgen Receptor-Dependent Mechanisms Mediating Drug Resistance in Prostate Cancer DOI Open Access
Marzieh Ehsani,

Faith Oluwakemi David,

Aria Baniahmad

et al.

Cancers, Journal Year: 2021, Volume and Issue: 13(7), P. 1534 - 1534

Published: March 26, 2021

Androgen receptor (AR) is a main driver of prostate cancer (PCa) growth and progression as well the key drug target. Appropriate PCa treatments differ depending on stage at diagnosis. Although androgen deprivation therapy (ADT) initially effective, eventually tumors develop resistance to within 2-3 years treatment onset leading castration resistant (CRPC). Castration usually mediated by reactivation AR signaling. Eventually, develops additional towards with antagonists that occur regularly, also mostly due bypass mechanisms activate This tumor evolution selection upon presumably based high degree heterogenicity plasticity allows cells proliferate adaptive signaling evolve pathways in resistance, including chemotherapy. The therapy-resistant phenotype associated more aggressiveness increased metastatic ability. By far, remains major cause failure lethality. In this review, various acquired intrinsic are AR‑dependent contribute will be discussed.

Language: Английский

Citations

61
Molecular mechanisms underlying the development of neuroendocrine prostate cancer DOI Creative Commons
Shiqin Liu, Busola R. Alabi, Qingqing Yin

et al.

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 57 - 68

Published: May 19, 2022

Language: Английский

Citations

44
Current and emerging therapies for neuroendocrine prostate cancer DOI
Busola R. Alabi, Shiqin Liu, Tanya Stoyanova

et al.

Pharmacology & Therapeutics, Journal Year: 2022, Volume and Issue: 238, P. 108255 - 108255

Published: July 27, 2022

Language: Английский

Citations

41
Temporal evolution reveals bifurcated lineages in aggressive neuroendocrine small cell prostate cancer trans-differentiation DOI Creative Commons
Chia-Chun Chen, Wendy Tran, Kai Song

et al.

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(12), P. 2066 - 2082.e9

Published: Nov. 22, 2023

Trans-differentiation from an adenocarcinoma to a small cell neuroendocrine state is associated with therapy resistance in multiple cancer types. To gain insight into the underlying molecular events of trans-differentiation, we perform multi-omics time course analysis pan-small model (termed PARCB), forward genetic transformation using human prostate basal cells and identify shared developmental, arc-like, entropy-high trajectory among all replicates. Further mapping single resolution reveals two distinct lineages defined by mutually exclusive expression ASCL1 or ASCL2. Temporal regulation groups transcription factors across developmental stages that cellular reprogramming precedes induction neuronal programs. TFAP4 ASCL1/2 feedback are identified as potential regulators ASCL2 expression. Our study provides temporal transcriptional patterns uncovers pan-tissue parallels between lung cancers, well connections normal states.

Language: Английский

Citations

36
Spatial Gene Expression Analysis Reveals Characteristic Gene Expression Patterns of De Novo Neuroendocrine Prostate Cancer Coexisting with Androgen Receptor Pathway Prostate Cancer DOI Open Access
Ryuta Watanabe, Noriyoshi Miura, Mie Kurata

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 8955 - 8955

Published: May 18, 2023

Neuroendocrine prostate carcinoma (NEPC) accounts for less than 1% of neoplasms and has extremely poorer prognosis the typical androgen receptor pathway-positive adenocarcinoma (ARPC). However, very few cases in which de novo NEPC APRC are diagnosed simultaneously same tissue have been reported. We report herein a 78-year-old man metastatic coexisting with ARPC treated at Ehime University Hospital. Visium CytAssist Spatial Gene Expression analysis (10× genetics) was performed using formalin-fixed, paraffin-embedded (FFPE) samples. The neuroendocrine signatures were upregulated sites, sites. TP53, RB1, or PTEN upregulation homologous recombination repair genes sites not downregulated. Urothelial markers elevated. Meanwhile, Rbfox3 SFRTM2 levels downregulated while fibrosis HGF, HMOX1, ELN, GREM1 tumor microenvironment NEPC. In conclusion, findings spatial gene expression patient accumulation basic data will help development novel treatments improve patients castration-resistant cancer.

Language: Английский

Citations

27
Clinical and translational relevance of intratumor heterogeneity DOI Creative Commons
Marie-Anne Goyette, Marla Lipsyc-Sharf, Kornélia Polyák

et al.

Trends in cancer, Journal Year: 2023, Volume and Issue: 9(9), P. 726 - 737

Published: May 27, 2023

Language: Английский

Citations

25
WNT5a Signaling through ROR2 Activates the Hippo Pathway to Suppress YAP1 Activity and Tumor Growth DOI
Keshan Wang, Fen Ma, Seiji Arai

et al.

Cancer Research, Journal Year: 2023, Volume and Issue: 83(7), P. 1016 - 1030

Published: Jan. 6, 2023

Noncanonical Wnt signaling by WNT5a has oncogenic and tumor suppressive activities, but downstream pathways mediating these specific effects remain to be fully established. In a subset of prostate cancer organoid culture xenograft models, inhibition synthesis stimulated growth, whereas or mimetic peptide (Foxy5) markedly suppressed growth. caused ROR2-dependent decrease in YAP1 activity, which was associated with increased phosphorylation MST1/2, LATS1, MOB1, YAP1, indicating Hippo pathway activation. Deletion MST1/2 abrogated the response. similarly activated ROR2-expressing melanoma cells, ROR2-negative cells Hippo. This suppression inhibitory NF2/Merlin that not observed cells. also mRNA encoding components including MST1 MST2 positively correlated clinical datasets. Conversely, ROR2 expression activity datasets, revealing WNT5a/ROR2 negative feedback loop modulate activity. Together findings identify activation as mechanism mediates indicate may predictive biomarker for responsiveness WNT5a-mimetic drugs.WNT5a through activates downregulate YAP1/TAZ suppress identifying potential patients could benefit from WNT5a-related agents.

Language: Английский

Citations

24