• Current checkpoint kinase inhibitors, like PV1019 or AZD7762, offer a higher level of specificity than their predecessors that can be exploited by combination with indenoisoquinolines. (aacrjournals.org)
  • We investigated whether the clinical exportin 1 (XPO1) inhibitor selinexor (KPT-330), when combined with pegylated liposomal doxorubicin (PLD) or doxorubicin hydrochloride, could overcome acquired drug resistance in multidrug-resistant human MM xenograft tumors, four different multidrug-resistant MM cell lines, or ex vivo MM biopsies from relapsed/refractory patients. (beds.ac.uk)
  • The combination of an XPO1 inhibitor and liposomal doxorubicin was highly effective against acquired drug resistance in in vitro MM models, in in vivo xenograft studies, and in ex vivo samples obtained from patients with relapsed/refractory myeloma. (beds.ac.uk)
  • DNA topoisomerases comprise an important family of enzymes that catalyse the induction of topological changes (e.g. relaxation/ supercoiling, catenation/decatenation and knotting/unknotting) in the DNA molecule. (eurekaselect.com)
  • Acquired drug resistance is the greatest obstacle to the successful treatment of multiple myeloma (MM). Despite recent advanced treatment options such as liposomal formulations, proteasome inhibitors, immunomodulatory drugs, myeloma-targeted antibodies, and histone deacetylase inhibitors, MM is still considered an incurable disease. (beds.ac.uk)
  • There is an up-front randomisation in four therapy arms with two cross-classifying factors of two stages (intensified vs. standard therapy and Ara C vs. Ara C+ mitoxantrone + m-AMSA). (clinicaltrials.gov)
  • In the field of breast cancer, two advances in targeted therapy have led to great strides in the understanding and treatment of breast cancer, namely hormonal therapy for estrogen positive receptor breast cancer and antibodies directed towards the inhibition of human epidermal growth factor receptor (HER)2. (biomedcentral.com)
  • Therapy consists of 1 to 2 induction cycles followed by up to 2 consolidation cycles. (drugs.com)
  • There are two general causes of antineoplastic therapy failure: Inherent genetic characteristics, giving cancer cells their resistance, which is rooted in the concept of cancer cell heterogeneity and acquired resistance after drug exposure. (wikipedia.org)
  • Topoisomerase II participates in various DNA metabolic processes, such as transcription, DNA replication, chromosome condensation, and decondensation, and is essential at the time of chromosome segregation following cell division ( 3 ). (aacrjournals.org)
  • 26 , 27 ] Two retrospective studies of patients with germline mutations in BRCA1 suggest that the women in these studies have improved survival compared with BRCA1 mutation-negative women. (cancer.gov)
  • In a family-based study among 551 women with BRCA1 or BRCA2 mutations, of the 259 women who had undergone bilateral prophylactic oophorectomy, 2 (0.8%) developed subsequent papillary serous peritoneal carcinoma, and 6 (2.8%) had stage I ovarian cancer at the time of surgery. (cancer.gov)
  • Lead has been shown to be an inhibitor of cell division, water uptake, and photosynthesis, eventually causing death to the plant. (wikipedia.org)
  • Mechanistic studies were performed to assess co-localization of topoisomerase II alpha (TOP2A), DNA damage, and siRNA knockdown of drug targets. (beds.ac.uk)
  • Since cancer is a genetic disease, two genomic events underlie acquired drug resistance: Genome alterations (e.g. gene amplification and deletion) and epigenetic modifications. (wikipedia.org)
  • Toward discovering new anti-cancer agents targeting topoisomerase IIα: a facile screening strategy adaptable to high throughput platform. (springermedizin.de)
  • 2 ] Therefore, high-grade serous adenocarcinomas arising from the fallopian tube and elsewhere in the peritoneal cavity, together with most ovarian epithelial cancers, represent extrauterine adenocarcinomas of Müllerian epithelial origin and are staged and treated similarly to ovarian cancer. (cancer.gov)
  • In addition, based on our preclinical data, we have initiated a phase I/II study with the XPO1 inhibitor selinexor and PLD (ClinicalTrials.gov NCT02186834). (beds.ac.uk)
  • the second induction cycle may be administered 2 to 5 weeks after the first induction cycle (if no unacceptable toxicity with previous cycle). (drugs.com)