ArticleCancer research2009
Targeting the Fanconi anemia/BRCA pathway circumvents drug resistance in multiple myeloma.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06536413 (Phase IB/II Study Combining All-Trans Retinoic Acid), which is not on this map. Cited by 67 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase IB/II Study Combining All-Trans Retinoic Acid (ATRA) With Carfilzomib Based Therapy in Plasma Cell Myeloma Patients Refractory to Carfilzomib
Who cites it
67 citing papers in PubMed, 109 citations in OpenAlex.
- Phase 1/2 Trial of Carfilzomib Plus High-Dose Melphalan Preparative Regimen for Salvage Autologous Hematopoietic Cell Transplantation Followed by Maintenance Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2018Trial
- An open-label phase I/II study of cyclophosphamide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed myeloma.European journal of haematology · 2015Trial
- Phase Ib/II trial of CYKLONE (cyclophosphamide, carfilzomib, thalidomide and dexamethasone) for newly diagnosed myeloma.British journal of haematology · 2015Trial
- Combination of high-dose melphalan and bortezomib as conditioning regimen for autologous peripheral blood stem cell transplantation in multiple myeloma.International journal of hematology · 2013Trial
- Bortezomib salvage followed by a Phase I/II study of bortezomib plus high-dose melphalan and tandem autologous transplantation for patients with primary resistant myeloma.British journal of haematology · 2012Trial
- Pegargiminase Suppresses the Fanconi Anemia Pathway and Promotes Melphalan-Induced DNA Double-Strand Breaks in Uveal Melanoma.Pigment cell & melanoma research · 2026Article
- Targeting MTPN sensitizes pancreatic cancer of wild-type BRCA1/2 to Cisplatin-based chemotherapy.Cancer gene therapy · 2025Article
- Targeting CLK2 and serine/arginine-rich splicing factors inhibits multiple myeloma through downregulating RAE1 by nonsense-mediated mRNA decay mechanism.Cancer science · 2025Article
- Repair of genomic interstrand crosslinks.DNA repair · 2024Review
- A high-throughput approach to identify BRCA1-downregulating compounds to enhance PARP inhibitor sensitivity.iScience · 2024Article
- Article
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- Review
- The mitochondrial pyruvate carrier complex potentiates the efficacy of proteasome inhibitors in multiple myeloma.Blood advances · 2023Article
- Disulfiram enhances the antitumor activity of cisplatin by inhibiting the Fanconi anemia repair pathway.Journal of Zhejiang University. Science. B · 2023Article
- The Role of DNA Repair in Genomic Instability of Multiple Myeloma.International journal of molecular sciences · 2022Review
- The BLM helicase is a new therapeutic target in multiple myeloma involved in replication stress survival and drug resistance.Frontiers in immunology · 2022Article
- Plasma cell dependence on histone/protein deacetylase 11 reveals a therapeutic target in multiple myeloma.JCI insight · 2021Article
- Review
- Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The Fanconi anemia/BRCA (FA/BRCA) DNA damage repair pathway plays a pivotal role in the cellular response to replicative stress induced by DNA alkylating agents and greatly influences drug response in cancer treatment. We recently reported that FA/BRCA genes are overexpressed and causative for drug resistance in human melphalan-resistant multiple myeloma cell lines. However, the transcriptional regulation of the FA/BRCA pathway is not understood. In this report, we describe for the first time a novel function of the NF-kappaB subunits, RelB/p50, as transcriptional activators of the FA/BRCA pathway. Specifically, our findings point to constitutive phosphorylation of IkappaB kinase alpha and subsequent alterations in FANCD2 expression and function as underlying events leading to melphalan resistance in repeatedly exposed multiple myeloma cells. Inhibiting NF-kappaB by small interfering RNA, blocking the IkappaB kinase complex with BMS-345541, or using the proteasome inhibitor bortezomib drastically reduced FA/BRCA gene expression and FANCD2 protein expression in myeloma cells, resulting in diminished DNA damage repair and enhanced melphalan sensitivity. Importantly, we also found that bortezomib decreases FA/BRCA gene expression in multiple myeloma patients. These results show for the first time that NF-kappaB transcriptionally regulates the FA/BRCA pathway and provide evidence for targeting Fanconi anemia-mediated DNA repair to enhance chemotherapeutic response and circumvent drug resistance in myeloma patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.