Bladder cancer (BC) poses a significant health challenge, particularly in metastatic cases, where the prognosis is unfavorable and therapeutic options are limited. Poly ADP-ribose polymerase (PARP) inhibitors have gained approval for use in various cancer types, but their application in BC remains controversial, despite the notable prevalence of DNA damage response alterations in advanced or metastatic urothelial carcinomas. In this report, we describe a 66-year-old heavy-smoking female diagnosed with muscle-invasive BC. She underwent multiple rounds of chemotherapy and radiation, yet her disease remained poorly controlled, leading to metastasis in the left obturator internus muscle. Comprehensive genomic profiling through FoundationOne Liquid CDx, examining a 324-gene panel using circulating tumor DNA from blood samples, revealed a pathogenic gene alteration (p.Q654fs*10, c.1960delC), suggesting potential eligibility for PARP inhibitor therapy. Remarkably, the patient achieved a complete response to talazoparib, prompting an optimal investigation into BC candidates for this promising therapy.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11025443 | PMC |
http://dx.doi.org/10.1177/17588359241245283 | DOI Listing |
Oncol Lett
March 2025
Program in Translational Medicine, Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samutprakarn 10540, Thailand.
Cholangiocarcinoma (CCA) is a biliary tract carcinoma that is challenging to treat due to its heterogeneity and limited treatment options. Genetic alterations in DNA damage response (DDR) pathways and homologous recombination (HR) defects are common in CCA. This has prompted interest in the use of ataxia telangiectasia and Rad3-related protein (ATR) and poly(ADP-ribose) polymerase (PARP) inhibitors to treat CCA.
View Article and Find Full Text PDFCancer Chemother Pharmacol
January 2025
Human Genetics Laboratory, Institute of Natural Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, MG, 37130-001, Brazil.
Purpose: Histone deacetylase 6 (HDAC6) plays a critical role in tumorigenesis and tumor progression, contributing to proliferation, chemoresistance, and cell motility by regulating microtubule architecture. Despite its upregulation in melanoma tissues and cell lines, the specific biological roles of HDAC6 in melanoma are not well understood. This study aims to explore the functional effects and underlying mechanisms of WT161, a selective HDAC6 inhibitor, in melanoma cell lines.
View Article and Find Full Text PDFBreast Cancer Res
January 2025
Department of Medicine (Hematology/Oncology), School of Medicine, University of California San Francisco, 1450 Third St, San Francisco, CA, 94158, USA.
Background: Poly (ADP-Ribose) polymerase inhibitors are approved for treatment of tumors with BRCA1/2 and other homologous recombination repair (HRR) mutations. However, clinical responses are often not durable and treatment may be detrimental in advanced cancer due to excessive toxicities. Thus we are seeking alternative therapeutics to enhance PARP-directed outcomes.
View Article and Find Full Text PDFFuture Med Chem
January 2025
Department of Medicinal Chemistry, Xiangya School of Pharmaceutical Sciences, Central South University, Hunan, China.
Reversible protein ubiquitination is a crucial factor in cellular homeostasis, with Ubiquitin-Specific Protease 1 (USP1) serving as a key deubiquitinase involved in DNA damage response (DDR) and repair mechanisms in cancer. While ubiquitin ligases have been extensively studied, research on the reverse process of ubiquitination, particularly the mechanisms involving USP1, remains relatively limited. USP1 is overexpressed in various cancers, influencing tumor initiation and progression by regulating multiple associated proteins.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States.
DNPH1 is responsible for eliminating the epigenetically modified nucleotide, 5-hydroxymethyl-2'-deoxyuridine 5'-monophosphate (hmdUMP), preventing formation of hmdUTP, a mutation-inducing nucleotide. Loss of DNPH1 activity sensitizes PARP inhibition-resistant BRCA-deficient cancers by causing incorporation of hmdUTP into DNA. Hydrolysis of hmdUMP by DNPH1 proceeds through a covalent intermediate between Glu104 and 2-deoxyribose 5-phosphate, followed by hydrolysis, a reaction cycle with two transition states.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!