Cancer Research @ UCC - Journal Articles

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    Exploiting somatic alterations as therapeutic targets in advanced and metastatic cervical cancer
    (Elsevier Inc., 2021-05-21) Crowley, F. J.; O'Cearbhaill, R. E.; Collins, Dearbhaile C.; National Institutes of Health; National Cancer Institute
    It is estimated that 604,127 patients were diagnosed with cervical cancer worldwide in 2020. While a small percentage of patients will have metastatic disease at diagnosis, a large percentage (15–61%) later develop advanced disease. For this cohort, treatment with systemic chemotherapy remains the standard of care, with a static 5-year survival rate over the last thirty years. Data on targetable molecular alterations in cervical cancer have lagged behind other more common tumor types thus stunting the development of targeted agents. In recent years, tumor genomic testing has been increasingly incorporated into our clinical practice, opening the door for a potential new era of personalized treatment for advanced cervical cancer. The interim results from the NCI-MATCH study reported an actionability rate of 28.4% for the cervical cancer cohort, suggesting a subset of patients may harbor mutations which that are targetable. This review sets out to summarize the key targeted agents currently under exploration either alone or in combination with existing treatments for cervical cancer.
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    Learning from medical litigation
    (American Society of Clinical Oncology, 2023-01-18) Forrest, Clara; Madden, Deirdre; O'Sullivan, Martin J.; O'Reilly, Seamus
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    HDAC inhibitors induce LIFR expression and promote a dormancy phenotype in breast cancer
    (Springer Nature Switzerland AG, 2021-07-10) Clements, Miranda E.; Holtslander, Lauren; Edwards, Courtney; Todd, Vera; Dooyema, Samuel D. R.; Bullock, Kennady; Bergdorf, Kensey; Zahnow, Cynthia A.; Connolly, Roisin M.; Johnson, Rachelle W.; U.S. Department of Defense; National Institutes of Health
    Despite advances in breast cancer treatment, residual disease driven by dormant tumor cells continues to be a significant clinical problem. Leukemia inhibitory factor receptor (LIFR) promotes a dormancy phenotype in breast cancer cells and LIFR loss is correlated with poor patient survival. Herein, we demonstrate that histone deacetylase inhibitors (HDACi), which are in phase III clinical trials for breast cancer, epigenetically induced LIFR and activated a pro-dormancy program in breast cancer cells. HDACi slowed breast cancer cell proliferation and reduced primary tumor growth. Primary breast tumors from HDACi-treated patients had increased LIFR levels and reduced proliferation rates compared to pre-treatment levels. Recent Phase II clinical trial data studying entinostat and azacitidine in metastatic breast cancer revealed that induction of several pro-dormancy genes post-treatment was associated with prolonged patient survival. Together, these findings suggest HDACi as a potential therapeutic avenue to promote dormancy, prevent recurrence, and improve patient outcomes in breast cancer.
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    All-trans retinoic acid (ATRA)-induced TFEB expression is required for myeloid differentiation in acute promyelocytic leukemia (APL)
    (John Wiley & Sons, Inc., 2019-12-06) Orfali, Nina; O'Donovan, Tracey R.; Cahill, Mary R.; Benjamin, Dalyia; Nanus, David M.; McKenna, Sharon L.; Gudas, Lorraine J.; Mongan, Nigel P.; Breakthrough Cancer Research; Haematology Education and Research Trust, Ireland; National Cancer Institute
    Objective: In acute promyelocytic leukemia (APL), normal retinoid signaling is disrupted by an abnormal PML-RAR alpha fusion oncoprotein, leading to a block in cell differentiation. Therapeutic concentrations of all-trans-retinoic acid (ATRA) can restore retinoid-induced transcription and promote degradation of the PML-RAR alpha protein. Autophagy is a catabolic pathway that utilizes lysosomal machinery to degrade intracellular material and facilitate cellular re-modeling. Recent studies have identified autophagy as an integral component of ATRA-induced myeloid differentiation.Methods: As the molecular communication between retinoid signaling and the autophagy pathway is not defined, we performed RNA sequencing of NB4 APL cells treated with ATRA and examined autophagy-related transcripts.Results: ATRA altered the expression of >80 known autophagy-related transcripts, including the key transcriptional regulator of autophagy and lysosomal biogenesis, TFEB (11.5-fold increase). Induction of TFEB and its transcriptional target, sequestosome 1 (SQSTM1, p62), is reduced in ATRA-resistant NB4R cells compared to NB4 cells. TFEB knockdown in NB4 cells alters the expression of transcriptional targets of TFEB and reduces CD11b transcript levels in response to ATRA.Conclusions: We show for the first time that TFEB plays an important role in ATRA-induced autophagy during myeloid differentiation and that autophagy induction potentiates leukemic cell differentiation (Note: this study includes data obtained from NCT00195156).
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    Biodiversity: the overlooked source of human health
    (Elsevier Inc., 2022-12-28) Linhares, Yuliya; Kaganski, Alexander; Agyare, Christian; Kurnaz, Isil A.; Neergheen, Vidushi; Kolodziejczyk, Bartlomiej; Kędra, Monika; Wahajuddin, Muhammad; El-Youssf, Lahcen; de la Cruz, Thomas Edison; Baran, Yusuf; Pešić, Milica; Shrestha, Uttam; Bakiu, Rigers; Allard, Pierre-Marie; Rybtsov, Stanislav; Pieri, Myrtani; Siciliano, Velia; Flores Bueso, Yensi; Global Young Academy
    Biodiversity is the measure of the variation of lifeforms in a given ecological system. Biodiversity provides ecosystems with the robustness, stability, and resilience that sustains them. This is ultimately essential for our survival because we depend on the services that natural ecosystems provide (food, fresh water, air, climate, and medicine). Despite this, human activity is driving an unprecedented rate of biodiversity decline, which may jeopardize the life-support systems of the planet if no urgent action is taken. In this article we show why biodiversity is essential for human health. We raise our case and focus on the biomedicine services that are enabled by biodiversity, and we present known and novel approaches to promote biodiversity conservation.