Review
Oncology
Ya-Fei Hu, Hai-Jie Hu, Heng-Chung Kung, Tian-Run Lv, Jun Yu, Fu-Yu Li
Summary: The efficacy of platinum-based chemotherapy (PtCh) for pancreatic cancer (PC) patients with DNA damage repair gene mutations (DDRm) remains uncertain. This study analyzed multiple studies and found that DDRm was associated with a longer overall survival (OS) in advanced-stage PC patients, regardless of PtCh exposure. The first-line PtCh (1L-PtCh) also improved progression-free survival (PFS) in advanced-stage PC with DDRm. However, for resected PC patients, the presence of DDRm did not significantly impact OS, whether they received PtCh or not. Further prospective trials are needed to verify the prognostic value of DDRm.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Manman Xu, Xi Huang, Cuimiao Zheng, Junming Long, Qingyuan Dai, Yangyang Chen, Jingyi Lu, Chaoyun Pan, Shuzhong Yao, Jie Li
Summary: This study investigates the role of NHEJ in platinum resistance in ovarian cancer and finds that XRCC4 in the NHEJ pathway specifically contributes to resistance by mitigating DNA damage caused by platinum drugs, providing preclinical evidence for targeting XRCC4 as a new strategy to combat cisplatin resistance in ovarian cancer treatment.
Article
Biochemistry & Molecular Biology
Dimitra T. Stefanou, Vassilis L. Souliotis, Roubini Zakopoulou, Michalis Liontos, Aristotelis Bamias
Summary: Ovarian cancer is the seventh most common cancer in women worldwide, and the current treatment involves surgery and chemotherapy. Resistance to platinum-based drugs remains a major challenge, and the functionality of DNA repair pathways significantly impacts tumor response to treatment. Therefore, studying novel therapeutic targets and biomarkers related to DNA repair is of great importance for the treatment and prognosis of ovarian cancer.
Review
Immunology
Yufei Xu, Fengli Zuo, Huiling Wang, Jing Jing, Xiujing He
Summary: ICB therapy has significantly changed the landscape of anticancer therapy, but only a subset of patients benefit from it and immune-related adverse events (irAEs) can occur. Finding predictive biomarkers to optimize patient outcomes and reduce toxicity risk is urgently needed. This review discusses current predictive and prognostic biomarkers for checkpoint immunotherapy in ovarian cancer (OC) and highlights emerging biomarkers to guide treatment with ICB.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Camille Evrard, Jerome Alexandre
Summary: Endometrial cancers are highly affected by microsatellite instability, showing sensitivity to immunotherapy and requiring molecular biology for better understanding. The phenotype is poorly understood in ovarian cancer but does exist. Examination of literature reveals the importance of deficient mismatch repair/microsatellite instability in gynecological cancers and the potential therapeutic and prognostic implications.
Review
Oncology
Fulvio Borella, Marco Mitidieri, Stefano Cosma, Chiara Benedetto, Luca Bertero, Stefano Fucina, Isabelle Ray-Coquard, Annalisa Carapezzi, Domenico Ferraioli
Summary: Mucinous ovarian cancer (MOC), a rare tumor, can be classified into early MOC and advanced MOC. Early MOC has a good prognosis and surgical treatment is the mainstay. However, some early-stage MOCs can relapse and exhibit aggressive behavior. Advanced MOC has a poor prognosis and radical surgery is recommended, although these tumors are chemo-resistant. Targeted therapies for MOC are currently under study but have not been approved yet.
Review
Oncology
Craig T. Wallington-Beddoe, Rachel L. Mynott
Summary: New approaches are needed to stratify multiple myeloma patients based on prognosis and therapeutic decision-making, however, insufficient information currently exists to utilize biomarkers to tweak treatment. With the increasing complexity of drug classes used to treat multiple myeloma, clinically useful biomarkers are crucial in guiding personalized patient management.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Oncology
Sweta Sharma Saha, Lucy Gentles, Alice Bradbury, Dominik Brecht, Rebecca Robinson, Rachel O'Donnell, Nicola J. Curtin, Yvette Drew
Summary: This study identified that genomic/transcriptomic and/or functional alterations in DDR pathways can determine therapy response, offering insights into personalized chemotherapy choices for ovarian cancer patients.
Article
Oncology
Mohammad Aslam Khan, Kunwar Somesh Vikramdeo, Sarabjeet Kour Sudan, Seema Singh, Annelise Wilhite, Santanu Dasgupta, Rodney Paul Rocconi, Ajay Pratap Singh
Summary: Resistance to platinum-based chemotherapy in ovarian cancer is a major challenge, with diverse underlying molecular mechanisms complicating management of the disease. Recent research has identified novel molecular targets for treatment planning and monitoring. The therapeutic landscape of ovarian cancer is evolving rapidly, with alternative therapies emerging for recurrent platinum-resistant disease.
SEMINARS IN CANCER BIOLOGY
(2021)
Article
Oncology
Hong Zheng, Tong Shu, Shan Zhu, Chao Zhang, Min Gao, Nan Zhang, Hongguo Wang, Jie Yuan, Zaixian Tai, Xuefeng Xia, Yuting Yi, Jin Li, Yanfang Guan, Yang Xiang, Yunong Gao
Summary: This study aimed to predict platinum sensitivity in epithelial ovarian cancer after initial cytoreductive surgery by integrating novel biomarkers and using next generation sequencing to analyze genomic features of ovarian tumors obtained from surgery. Specific genetic features such as positive SBS10a signature, FAM175A LOH, and negative WGD were significantly associated with platinum-sensitive patients, leading to longer progress-free survival. A lasso regression model incorporating these biomarkers showed high accuracy in predicting platinum sensitivity, which was further validated in an independent cohort from the TCGA dataset.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Griffin Wright, Manoj Sonavane, Natalie R. Gassman
Summary: STAT3 is identified as a novel regulator of XRCC1, with its activation through the IL-6 signaling pathway increasing the expression level of XRCC1 and impacting its role in triple negative breast cancer. The upregulation of XRCC1 is associated with the aggressiveness and chemotherapeutic resistance in cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Katharina Doetzer, Friederike Schlueter, Franz Edler von Koch, Christine E. Brambs, Sabine Anthuber, Sergio Frangini, Bastian Czogalla, Alexander Burges, Jens Werner, Sven Mahner, Barbara Mayer
Summary: Integrin alpha 2 beta 1 has been identified as a prognostic and predictive marker in primary ovarian cancer, showing significant correlations with ERα, EGFR, immune cell infiltration, and PD-L1 expression. High alpha 2 beta 1 expression is associated with shorter survival, serving as an independent prognostic factor for patients' progression-free and platinum-free intervals. It has the potential to stratify patients for chemotherapy and immunotherapy and design new targeted treatment strategies.
Review
Biochemistry & Molecular Biology
Carolina Maria Sassu, Innocenza Palaia, Serena Maria Boccia, Giuseppe Caruso, Giorgia Perniola, Federica Tomao, Violante Di Donato, Angela Musella, Ludovico Muzii
Summary: Ovarian cancer is the second leading cause of death in women with gynecological cancer, with poor prognosis, especially in platinum-resistant disease. Efforts have been made to define new biomarkers, with circulating biomarkers being detected non-invasively but potentially requiring expensive techniques.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Hanlin Ma, Gonghua Qi, Fang Han, Wei Lu, Jiali Peng, Rongrong Li, Shi Yan, Cunzhong Yuan, Beihua Kong
Summary: This study found that the overexpression of HMGB3 is associated with shorter overall survival and drug resistance in high-grade serous ovarian carcinoma. HMGB3 interacts with PARP1 to promote PARPi resistance, and targeted inhibition of HMGB3 may overcome PARPi resistance in ovarian cancer therapy.
CELL DEATH & DISEASE
(2022)
Review
Oncology
Sandra Pavicevic, Sophie Reichelt, Deniz Uluk, Isabella Lurje, Cornelius Engelmann, Dominik P. Modest, Uwe Pelzer, Felix Krenzien, Nathanael Raschzok, Christian Benzing, Igor M. Sauer, Sebastian Stintzing, Frank Tacke, Wenzel Schoening, Moritz Schmelzle, Johann Pratschke, Georg Lurje
Summary: Cholangiocarcinoma is a rapidly increasing global malignancy of the biliary tract, often presenting with advanced or unresectable disease. Biomarkers obtained from patients' serum or tumor tissue could help guide therapy and identify those at higher risk of recurrence. Genetic aberrations in cholangiocarcinoma have also been linked with improved response to targeted therapies. This review provides an overview of prognostic and predictive biomarkers in cholangiocarcinoma.
Review
Oncology
Rachel Abbotts, Anna J. Dellomo, Feyruz Rassool
Summary: BRCA1 and BRCA2 play important roles in DNA repair and mutations in these genes increase the risk of cancer. In addition to BRCA mutations, mutations in other DNA repair genes can also lead to a BRCAness phenotype in tumors. PARP inhibitors can effectively treat tumors with BRCA mutations or BRCAness. To broaden the use of PARP inhibitors, studies have focused on combination strategies that induce BRCAness. This review summarizes the current status of drug-induced BRCAness in combination with PARP inhibitors for enhanced cancer treatment.
Article
Oncology
Ardalan Mahmoodi, Ahmed Shoqafi, Ping Sun, Vasily Giannakeas, Cezary Cybulski, Sharon Nofech-Mozes, Jean-Yves Masson, Sudha Sharma, Amir Abbas Samani, Srinivasan Madhusudan, Steven A. Narod, Mohammad R. Akbari
Summary: The study found that high RECQL protein levels are associated with improved survival rates in breast cancer patients who are ER-positive, but no significant association was found in ER- patients. Additionally, in ER-negative patients receiving tamoxifen treatment, high RECQL protein levels may be associated with better survival rates.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Rachael Nicholson, Ana Catarina Menezes, Aleksandra Azevedo, Adam Leckenby, Sara Davies, Claire Seedhouse, Amanda Gilkes, Steve Knapper, Alex Tonks, Richard L. Darley
Summary: This study found that PKC epsilon is significantly overexpressed in acute myeloid leukemia (AML) and is associated with reduced complete remission induction and disease-free survival. Additionally, PKC epsilon overexpression confers resistance to the chemotherapeutic agent daunorubicin by upregulating the expression of the efflux pump P-GP.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Reem Ali, Mustapha Aouida, Abdallah Alhaj Sulaiman, Srinivasan Madhusudan, Dindial Ramotar
Summary: Cisplatin is one of the oldest chemotherapeutic agents and has been used to treat various types of cancer. However, tumor cells often develop resistance mechanisms, limiting the effectiveness of cisplatin treatment. Extensive molecular and genetic profiling of patients is needed to identify individuals who can benefit from cisplatin therapy, and combining it with targeted therapies may improve treatment outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Harry H. Jenkins, Ana A. Tellechea Lopez, Francesco Saverio Tarantini, Hannah Tomlin, Danielle Scales, I-Ning Lee, Siyu Wu, Ralph Hyde, Katarzyna Lis-Slimak, Timothy Byaruhanga, Jamie L. Thompson, Sara Pijuan-Galito, Lara Doolan, Kazuyo Kaneko, Penny Gwynne, Caroline Reffin, Emily Park, Jayasree Dey, Jack Hill, Asta Arendt-Tranholm, Amy Stroud, Moira Petrie, Chris Denning, Andrew Benest, Claire Seedhouse
Summary: Polymerase chain reaction (PCR) has been proven to be the gold-standard for SARS-CoV-2 detection. Performing a non-invasive one-step RT-qPCR assay directly on saliva specimens simplifies sample collection, reduces processing time and costs. The assay demonstrates good sensitivity and concordance.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan
Summary: Platinum resistance is a major challenge in ovarian cancer treatment. This study comprehensively evaluated the expression and function of Mre11 in epithelial ovarian cancers, and found that overexpression of Mre11 was associated with aggressive phenotype and poor progression free survival. In addition, Mre11 gene amplification was observed in a subset of serous tumors and correlated with Mre11 mRNA levels. Furthermore, Mre11 overexpression at the transcriptomic level was linked with poor survival. Preclinical experiments showed that depletion or blockade of Mre11 reversed platinum resistance in ovarian cancer cells, and selective cytotoxicity was observed in platinum-sensitive XRCC1 deficient cells. These findings suggest that pharmaceutical development of Mre11 inhibitors could be a promising clinical strategy for sensitizing ovarian cancer to platinum and inducing synthetic lethality.
NPJ PRECISION ONCOLOGY
(2022)
Article
Oncology
Daisy B. Haigh, Corinne L. Woodcock, Jennifer Lothion-Roy, Anna E. Harris, Veronika M. Metzler, Jenny L. Persson, Brian D. Robinson, Francesca Khani, Mansour Alsaleem, Atara Ntekim, Srinivasan Madhusudan, Melissa B. Davis, Kristian B. Laursen, Lorraine J. Gudas, Catrin S. Rutland, Michael S. Toss, Nathan Archer, Zsuzsanna Bodi, Emad A. Rakha, Rupert G. Fray, Jennie N. Jeyapalan, Nigel P. Mongan
Summary: This study investigated whether therapies targeting the epitranscriptome can suppress androgen signalling in prostate cancer. The results showed that METTL3 is aberrantly expressed in prostate cancer patients and that knockdown or inhibition of METTL3 can significantly alter the basal and androgen-regulated transcriptome in prostate cancer, suggesting that targeting m6A could be a novel approach to modulate androgen signalling in prostate cancer.
Article
Oncology
Amit Bahl, William Wilson, Jessica Ball, Emily Renninson, Sidharth Dubey, Alicia Bravo, Emily Foulstone, Saiqa Spensley, Rebecca Bowen, Janine Mansi, Simon Waters, Pippa Riddle, Duncan Wheatley, Peter Stephens, Pavel Bezecny, Srinivasan Madhusudan, Mark Verrill, Jeremy Braybrooke, Charles Comins, Vivek Mohan, Abigail Gee, Hannah Kirk, Alison Markham, Heidi Evans, Eve Watson, Mark Callaway, Sylvia Pearson, Allan Hackshaw, Mark Churn
Summary: In HER2-negative MBC patients, three-weekly cabazitaxel does not significantly improve progression-free survival compared to weekly paclitaxel, but it has a lower risk of peripheral neuropathy and better quality of life outcomes.
Article
Cell Biology
Ayat Lashen, Michael S. Toss, Wakkas Fadhil, Georgette Oni, Srinivasan Madhusudan, Emad Rakha
Summary: This study aimed to compare the performance of Oncotype DX with conventional clinicopathological parameters in ER+/HER2- breast cancer. The results showed a significant correlation between Oncotype DX and tumor grade, type, ER and PR expression, and Ki67 index. Therefore, these tumor features can be used as surrogate markers in certain scenarios.
Article
Medicine, General & Internal
Sara A. Hurvitz, Roberto Hegg, Wei-Pang Chung, Seock-Ah Im, William Jacot, Vinod Ganju, Joanne Wing Yan Chiu, Binghe Xu, Erika Hamilton, Srinivasan Madhusudan, Hiroji Iwata, Sevilay Altintas, Jan-Willem Henning, Giuseppe Curigliano, Jose Manuel Perez-Garcia, Sung-Bae Kim, Vanessa Petry, Chiun-Sheng Huang, Wei Li, Jean-Sebastien Frenel, Silvia Antolin, Winnie Yeo, Giampaolo Bianchini, Sherene Loi, Junji Tsurutani, Anton Egorov, Yali Liu, Jillian Cathcart, Shahid Ashfaque, Javier Cortes
Summary: In the DESTINY-Breast03 trial, trastuzumab deruxtecan showed superior progression-free survival compared to trastuzumab emtansine in patients with HER2-positive metastatic breast cancer. The study aimed to compare the efficacy and safety of trastuzumab deruxtecan versus trastuzumab emtansine. The results demonstrated that trastuzumab deruxtecan had the longest reported median progression-free survival and improved overall survival, reaffirming its role as the standard of care in the second-line setting.
Review
Pharmacology & Pharmacy
Juliette Brownlie, Sanat Kulkarni, Mashael Algethami, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan
Summary: DNA repair targeted therapeutics, such as PARP inhibitors, have shown promising results in the treatment of BRCA germline deficient breast and ovarian cancer. However, not all patients respond to this treatment due to intrinsic or acquired resistance. Therefore, the exploration of other synthetic lethality approaches, including ATM, ATR, and WEE1 inhibitors, is currently an active area in cancer research.
CURRENT OPINION IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jenna R. James, Johnathan Curd, Jennifer C. Ashworth, Mays Abuhantash, Martin Grundy, Claire H. Seedhouse, Kenton P. Arkill, Amanda J. Wright, Catherine L. R. Merry, Alexander Thompson
Summary: A 3D model of the bone marrow niche has been developed using a synthetic peptide hydrogel (SAPH) to screen FDA-approved drugs for acute myeloid leukemia (AML). The optimized stiffness of SAPH affects AML cell proliferation and Salinomycin shows efficacy in AML patient samples. Vidofludimus is not sensitive to AML cells in the hydrogel models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Hiu Tang, Sanat Kulkarni, Christina Peters, Jasper Eddison, Maryam Al-Ani, Srinivasan Madhusudan
Summary: Despite advances in chemotherapy and surgery, patients with advanced ovarian cancer still have poor survival outcomes. Platinum-based systemic chemotherapy can lead to a high response rate, but most patients will experience recurrence and succumb to the disease. The use of PARP inhibitors in BRCA germ-line-deficient and/or platinum-sensitive epithelial ovarian cancers has improved survival, but resistance remains a clinical challenge. This review discusses the current clinical state of PARP inhibitors and other targeted approaches in epithelial ovarian cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Hiu Tang, Daniel Yeo, Karen De Souza, Omar Ahmad, Tahir Shafiq, Okezie Ofor, Anjana Anand, Syed Karim, Sarah Khan, Srinivasan Madhusudan
Summary: CDK4/6 inhibitors can significantly increase progression-free survival in ER+/HER2- advanced breast cancer patients. There is no significant difference in PFS and OS between different drugs in real-world evaluation. De novo disease and PR+ disease have longer PFS and OS. Very elderly patients have shorter PFS and OS.
Article
Biochemical Research Methods
Francesco Saverio Tarantini, Siyu Wu, Harry Jenkins, Ana Tellechea Lopez, Hannah Tomlin, Ralph Hyde, Katarzyna Lis-Slimak, Jamie Louise Thompson, Sara Pijuan-Galito, Danielle Scales, Kazuyo Kaneko, Jayasree Dey, Emily Park, Jack Hill, I-Ning Lee, Lara Doolan, Asta Arendt-Tranholm, Chris Denning, Claire Seedhouse, Andrew Benest
Summary: Since mid-2020, there have been difficulties in standardizing and administering nasopharyngeal swabs, leading to testing fatigue and reduced confidence in results. On the other hand, saliva-based PCR testing is gaining momentum as a non-invasive, highly sensitive, and accurate method.
METHODS AND PROTOCOLS
(2022)