DNA damage response as a therapeutic target in gynecological cancers

Purpose of review: The proven activity of poly ADP ribose polymerase (PARP) inhibitors in BRCA-mutated homologous recombination deficient (HRD) ovarian cancer has led to the availability to patients with ovarian cancer of the first targeted therapy with an associated predictive biomarker. Our focus has recently turned towards expanding the clinical utility of PARP inhibitors beyond BRCA mutated ovarian cancer, and to a search for novel targets within DNA damage response (DDR). Recent findings: Early trials in unselected patients with ovarian cancer showed responses to PARP inhibition in BRCA-wildtype ovarian cancer, and recent genomic studies have demonstrated that germline or somatic aberrations in other homologous recombination genes are present in a significant proportion of ovarian cancers. In addition, PARP inhibition may be of value in molecularly defined subsets of endometrial or cervical cancers. Novel DDR inhibitors such as ATR, ATM, WEE1 or DNA-PK inhibitors are also being tested in patients. Finally, combinatorial strategies of DDR inhibitors with antiangiogenic agents, phosphoinositide 3-kinase inhibitors or immunotherapies may further increase therapeutic efficacy. Summary: In the future, patients with gynaecological malignancies may be rationally selected for PARP inhibition on the basis of comprehensive evaluation of homologous recombination genomic alterations, or HRD assays. Furthermore, novel DDR inhibitors have the potential to expand the repertoire of th...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: GYNECOLOGIC CANCER: Edited by Martin Gore Source Type: research

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Conclusion MTDH is pro-oncogenic factor playing multifaceted and diverse roles in cancer progression. Its association and central role in regulating signaling pathways such a MAPK, wnt/β-catenin, PI3K/AkT, NF-κβ pathways in various cancers shows that it plays a vital role in metastasis. MTDH contribution to chemo and radiotherapy resistance provides a new direction for the development of anticancer therapeutics. Multiple mechanisms converge to promote expression of MTDH in cancers. Further studies are therefore warranted to determine whether the elevated MTDH expression has prognostic value for development...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study aimed to investigate whether combining anti-PD-L1 Atezolizumab with BEV may have a synergistic effect and enhance the efficacy of both treatments in cisplatin resistant epithelial ovarian cancer (CREOC). We retrospectively analyzed 124 epithelial ovarian cancer (EOC) patients from Gynecologic Oncology Department of Tianjin Cancer Hospital between January 2013 and June 2018, who all were diagnosed with cisplatin resistance due to progressing
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Clara Degos1, Mellie Heinemann2, Julien Barrou2, Nicolas Boucherit1, Eric Lambaudie2, Ariel Savina3†, Laurent Gorvel1* and Daniel Olive1* 1Tumor Immunology Team, IBISA Immunomonitoring Platform, Cancer Research Center of Marseillle, INSERM U1068, CNRS U7258, Institut Paoli-Calmettes, Aix-Marseille University, Marseille, France 2Department of Surgical Oncology 2, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Aix-Marseille University, Marseille, France 3Institut Roche, Boulogne Billancourt, France Endometrial Cancer is the most common cancer in the female genital tract in developed countries, and with its ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Authors: Kong TW, Ryu HS, Kim SC, Enomoto T, Li J, Kim KH, Shim SH, Wang PH, Therasakvichya S, Kobayashi Y, Lee M, Shi T, Lee SW, Mikami M, Nagase S, Lim MC, Wang J, Wilailak S, Kim SW, Hong SH, Tan DS, Mandai M, Chang SJ, Huang RYJ, Ushijima K, Lee JY, Chen X, Ochiai K, Lee TS, Yang B, Kalam F, Lv Q, Ahmad MF, Yaznil MR, Modi KB, Manopunya M, Jeong DH, Lertkhachonsuk AA, Chung HH, Watari H, Jeon S Abstract The Asian Society of Gynecologic Oncology International Workshop 2018 on gynecologic oncology was held in the Ajou University Hospital, Suwon, Korea on the 24th to 25th August 2018. The workshop was an opportuni...
Source: Journal of Gynecologic Oncology - Category: OBGYN Tags: J Gynecol Oncol Source Type: research
Publication date: Available online 16 November 2018Source: Clinica Chimica ActaAuthor(s): Eseosaserea Igbinigie, Fengbiao Guo, Shi-Wen Jiang, Cullen Kelley, Jinping LiAbstractDickkopf-1 (Dkk1)’s dysregulation has been implicated in the pathogenesis of a variety of cancers. It is part of the Dkk family of proteins that includes Dkk2, Dkk3 and Dkk4. This family of secreted proteins shares similar conserved cysteine domains and inhibits the Wnt/b-catenin pathway by causing proteasomal B-catenin degradation, inducing apoptosis, and preventing cell proliferation. Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading ...
Source: Clinica Chimica Acta - Category: Laboratory Medicine Source Type: research
Abstract Dickkopf-1 (Dkk1)'s dysregulation has been implicated in the pathogenesis of a variety of cancers. It is part of the Dkk family of proteins that includes Dkk2, Dkk3 and Dkk4. This family of secreted proteins shares similar conserved cysteine domains and inhibits the Wnt/b-catenin pathway by causing proteasomal B-catenin degradation, inducing apoptosis, and preventing cell proliferation. Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer mortality in the United States due to the late stage of diagnosis and the limited effectiveness of current therapy. Dkk1 is found increased in PADC...
Source: International Journal of Clinical Chemistry - Category: Chemistry Authors: Tags: Clin Chim Acta Source Type: research
Mutations in Tumor Protein P53 (p53) are expressed in a variety of human cancers such as cholangiocarcinoma, melanoma, colon cancer, rectal cancer, ovarian cancer, endometrial cancer, non-small cell lung cancer (NSCLC), glioblastoma, uterine cervical cancer, head and neck cancer, breast cancer, pancreatic cancer, and bladder cancer. The p53 protein is involved in determining whether DNA is repaired or the damaged cell undergoes apoptosis – thus acting as a tumor suppressor by regulating cell division. Mutations in the p53 protein can reduce or eliminate its tumor suppressor function or interfere with wild type p53 in...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research
AbstractPurpose of ReviewThe purpose of this review is to update readers on recent advancements in the use of immune checkpoint inhibitors for the treatment of ovarian, uterine, and cervical cancers.Recent FindingsImmunotherapy has emerged as a novel therapeutic paradigm in the treatment of gynecologic malignancies. Currently, immune checkpoint inhibitors are approved for use across five solid malignancies, with recent approval of pembrolizumab in patients with MMR-deficient, recurrent, solid tumors in a disease site agnostic fashion. Phase 3 clinical trials are being conducted in the gynecologic cancer arena to determine ...
Source: Current Obstetrics and Gynecology Reports - Category: OBGYN Source Type: research
Authors: Suh DH, Kim M, Lee KH, Eom KY, Kjeldsen MK, Mirza MR, Kim JW Abstract In 2017, 10 topics were selected as major clinical research advances in gynecologic oncology. For cervical cancer, efficacy and safety analysis results of a 9-valent human papillomavirus (HPV) vaccine and long-term impact of reduced dose of quadrivalent vaccine were updated. Brief introduction of KEYNOTE trials of pembrolizumab, a monoclonal antibody that blocks the interaction between programmed death (PD)-1 and its ligands, PD-L1 and PD-L2, followed. Tailored surveillance programs for gynecologic cancer related with Lynch syndrome and ...
Source: Journal of Gynecologic Oncology - Category: OBGYN Tags: J Gynecol Oncol Source Type: research
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