Article
Biochemistry & Molecular Biology
Yumiko Tahira, Katsuya Sakai, Hiroki Sato, Ryu Imamura, Kunio Matsumoto
Summary: The researchers found that the residues N127, V140, and K144 at the NK1 dimer interface play important roles in Met activation by HGF. Mutant NK1 proteins with alanine replacements at these residues lost their ability to activate Met, while mutant HGF proteins with the same replacements retained their activity, suggesting a distinction in the structural basis for NK1-dependent Met dimer formation and HGF-dependent Met activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Grazia Bellese, Erica Tagliatti, Maria Cristina Gagliani, Sara Santamaria, Pietro Arnaldi, Paola Falletta, Paola Rusmini, Michela Matteoli, Patrizio Castagnola, Katia Cortese
Summary: This study investigated the effects of a drug called Neratinib on ERBB2+ breast cancer cells. It was found that Neratinib inhibited critical cell survival processes, including multiple signaling pathways and DNA damage response, inducing cell cycle arrest, early apoptosis, and transient autophagy. These effects may be mediated by altered expression of the chromatin transcription factors TFEB and TFE3.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Chloe J. Peach, Laura E. Kilpatrick, Jeanette Woolard, Stephen J. Hill
Summary: VEGF-A is an important mediator of angiogenesis that signals primarily through VEGF receptor 2 (VEGFR2). In this study, researchers investigated the differences in ligand binding kinetics of VEGF-A isoforms in living cells expressing both VEGFR2 and neuropilin-1 (NRP1). They found that despite the selectivity for VEGFR2, one isoform had distinct binding kinetics when interacting with the VEGFR2/NRP1 complex, while the other isoform showed kinetics similar to VEGFR2 alone.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Review
Oncology
Mary Luz Uribe, Ilaria Marrocco, Yosef Yarden
Summary: Growth factors like epidermal growth factor (EGF) can promote cell division and migration, but cancer hijacks these mechanisms for tumor growth and metastasis. Over-production and mutations of EGF and EGFR are common in various cancers, making them popular targets for anti-cancer therapies. The activation of EGFR triggers a series of molecular switches controlling gene expression, with implications for drug resistance and metastasis.
Review
Endocrinology & Metabolism
Artak Labadzhyan, Shlomo Melmed
Summary: Molecular therapeutic targets in growth hormone-secreting adenomas have potential for drug development, including surface receptors recognized by approved drugs and markers for new drug candidates. Current medical therapies control the disease in most patients but the degree of control varies and is related to disease aggressiveness and tumor factors. Understanding the mechanisms behind these molecular markers and their relationship to outcomes holds promise for expanding treatment options and personalized approaches.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Hematology
Imane Boukhatem, Samuel Fleury, Melanie Welman, Jessica Le Blanc, Chantal Thys, Kathleen Freson, Myron G. Best, Thomas Wurdinger, Bruce G. Allen, Marie Lordkipanidze
Summary: Research has shown that circulating BDNF levels appear to regulate platelet activation, aggregation, and secretion through activation of a truncated TrkB receptor and downstream kinase-dependent signaling. BDNF not only plays a role in neurons but also has important functions in platelets.
Review
Biochemistry & Molecular Biology
Mariam Ahmed Galal, Samhar Samer Alouch, Buthainah Saad Alsultan, Huda Dahman, Nouf Abdullah Alyabis, Sarah Ammar Alammar, Ahmad Aljada
Summary: This comprehensive review thoroughly explores the intricate involvement of insulin receptor isoforms and insulin-like growth factor receptors in the insulin and insulin-like growth factor signaling pathway, emphasizing their crucial roles in cancer development and resistance to anti-cancer drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Jing Bi, Zhihui Wu, Xin Zhang, Taoling Zeng, Wanjun Dai, Ningyuan Qiu, Mingfeng Xu, Yikai Qiao, Lang Ke, Jiayi Zhao, Xinyu Cao, Qi Lin, Xiao Lei Chen, Liping Xie, Zhong Ouyang, Jujiang Guo, Liangkai Zheng, Chao Ma, Shiying Guo, Kangmei Chen, Wei Mo, Guo Fu, Tong-Jin Zhao, Hong-Rui Wang
Summary: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor outcome and lacks approved targeted therapy. Overexpression of epidermal growth factor receptor (EGFR) is found in more than 50% TNBC and is suggested as a driving force in TNBC progression. However, targeting EGFR using antibodies shows no significant benefits for TNBC patients. This study reveals that deficiency of TMEM25 allows EGFR monomer to activate STAT3 independent of ligand binding, promoting TNBC progression, and suggests TMEM25 as a potential targeted therapy for TNBC.
NATURE COMMUNICATIONS
(2023)
Article
Neurosciences
Anna Gemza, Cinzia Barresi, Jakob Proemer, Jasmin Hatami, Margarita Lazaridis, Ruth Herbst
Summary: In the activation pathway of MuSK, only MuSK internalization is increased by Agrin stimulation, while Lrp4 remains unaffected, and MuSK kinase activity is insufficient to induce MuSK internalization. In addition, inhibition of Dynamin has no effect on MuSK internalization and signaling.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Jose A. Lopez-Mejia, Luis F. Tallabs-Utrilla, Pablo Salazar-Sojo, Jessica C. Mantilla-Ollarves, Manuel A. Sanchez-Carballido, Leticia Rocha-Zavaleta
Summary: This study investigates the expression and effects of c-Kit in triple-negative breast cancer (TNBC) and finds that TNBC cells express functional c-Kit, which shows a strong response to Nilotinib and may be considered as a candidate drug for TNBC treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Cancan Lyu, Yuanchao Ye, Maddison M. Lensing, Kay-Uwe Wagner, Ronald J. Weigel, Songhai Chen
Summary: In HER2(+) breast cancer, overactivation of HER2 leads to aberrant G(i/o)-GPCR signaling, promoting cancer progression and resistance to HER2-targeted therapy. Pharmacologically deactivating GPCR signaling can block tumor growth and enhance therapeutic efficacy.
Article
Multidisciplinary Sciences
Lucia Janacova, Michaela Stenckova, Petr Lapcik, Sarka Hrachovinova, Pavla Bouchalova, David Potesil, Roman Hrstka, Petr Muller, Pavel Bouchal
Summary: Catechol-O-methyl transferase (COMT) is involved in the detoxification of catechol estrogens and suppresses migration potential of breast cancer cells. In this study, the role of COMT in estrogen receptor-dependent breast cancer metastasis was investigated. Overexpression of COMT was found to decrease cell invasion and affect the transcriptome, proteome, and interactome of MCF7 cells. The study also revealed that COMT interacts with proteins involved in the MET signaling pathway, suggesting its involvement in tumor suppression.
SCIENTIFIC REPORTS
(2023)
Review
Biochemistry & Molecular Biology
Dongying Chen, Michael Simons
Summary: PLC gamma 1, a member of the PLC family, plays a crucial role as a signal transducer by hydrolyzing membrane lipid to generate second messengers. Deficiency of PLC gamma 1 in animal models and gain-of-function mutations in human endothelial cancers highlight its significant physiological role in the endothelial system. Understanding the physiological and molecular functions of PLC gamma 1 can provide insights for future research in the context of endothelial cells.
Article
Oncology
Simona Gallo, Annapia Vitacolonna, Paolo Comoglio, Tiziana Crepaldi
Summary: The MET oncogene interacts with glutamate receptors in breast cancer cells, promoting migration and invasion. Inhibition of glutamate receptors can reduce the effects of hepatocyte growth factor (HGF) on cell migration and invasion. In triple-negative breast cancer cells, the NMDAR2B subunit is coexpressed with the MET protein, and inhibiting NMDAR can weaken the effects of HGF.
Review
Biochemistry & Molecular Biology
Mohammed A. Mansour, Valentina S. Caputo, Eiman Aleem
Summary: GFRs and RTKs play essential roles in physiological processes, and their dysregulation is associated with various diseases, particularly cancer. Novel targeted therapies are being developed to inhibit the activity of growth factor receptors and their downstream kinases in different types of cancer.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2021)
Article
Oncology
Niamh M. Keegan, Simon J. Furney, Janice M. Walshe, Giuseppe Gullo, M. John Kennedy, Diarmuid Smith, John McCaffrey, Catherine M. Kelly, Keith Egan, Jennifer Kerr, Mark Given, Peter O'Donovan, Andres Hernando, Ausra Teiserskiene, Imelda Parker, Elaine Kay, Angela Farrelly, Aoife Carr, Giulio Calzaferri, Ray McDermott, Maccon M. Keane, Liam Grogan, Oscar Breathnach, Patrick G. Morris, Sinead Toomey, Bryan T. Hennessy
Summary: This study highlighted the significance of PIK3CA gene in HER2 positive breast cancer and investigated the clinical activity of combination therapy with the PI3K inhibitor copanlisib and trastuzumab in breast cancer patients.
Review
Oncology
Enea Ferlizza, Rossella Solmi, Michela Sgarzi, Luigi Ricciardiello, Mattia Lauriola
Summary: Colorectal cancer (CRC) ranks as the third most common cancer worldwide, emphasizing the significance of early detection. Screening through fecal occult blood tests has shown to reduce CRC incidence and mortality, however, low participation rates and false positives are key challenges. Recent research has focused on new fecal tests, biomarkers, and liquid biopsy methods to enhance accuracy and participation in CRC screening.
Article
Oncology
A. J. Eustace, S. F. Madden, J. Fay, D. M. Collins, E. W. Kay, K. M. Sheehan, S. Furney, B. Moran, A. Fagan, P. G. Morris, A. Teiserskiene, A. D. Hill, L. Grogan, J. M. Walshe, O. Breathnach, C. Power, D. Duke, K. Egan, W. M. Gallagher, N. O'Donovan, J. Crown, S. Toomey, B. T. Hennessy
Summary: The study found that patients with high levels of lymphocyte counts before treatment were more likely to achieve a complete pathological response after chemotherapy. For patients who achieved a pCR after chemotherapy, their immune response may return to baseline after only one cycle of treatment. In patients who did not achieve a pCR, neoadjuvant treatment may stimulate lymphocyte influx into the tumor.
BREAST CANCER RESEARCH AND TREATMENT
(2021)
Article
Oncology
R. J. Keogh, M. Milewski, K. Browne, K. Egan, M. A. Hennessy, Z. Coyne, D. Cowzer, A. Linehan, B. T. Hennessy, L. Grogan, P. G. Morris, O. S. Breathnach
Summary: The study aimed to understand the impact of paclitaxel chemotherapy on breath alcohol in an Irish population. Results showed that while some patients had breath alcohol levels above the threshold for professional, learner or novice drivers, overall, weekly paclitaxel infusions are unlikely to pose significant risks to patients driving.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2021)
Article
Medicine, General & Internal
Orla Fitzpatrick, Roisin Ni Dhonaill, Anna Linehan, Zac Coyne, Maeve Hennessy, Maeve Clarke, Elizabeth McGee, Fiona Barrett, Deborah O'Doherty, Carla Matassa, Teresa Doyle, Allyson Christie, Bryan Hennessy, Liam Grogan, Patrick G. Morris, Oscar S. Breathnach, Darren Cowzer
Summary: By implementing screening measures for COVID-19 symptoms and ensuring safety protocols, it was possible to safely and continuously deliver systemic anti-cancer therapy during the COVID-19 pandemic.
IRISH JOURNAL OF MEDICAL SCIENCE
(2022)
Letter
Medicine, General & Internal
Niall T. Hennessy, Sinead Toomey, Virginie Gautier, Sophie O'Reilly, Eoghan de Barra, Emer O. Hanrahan, Bryan T. Hennessy
IRISH JOURNAL OF MEDICAL SCIENCE
(2022)
Article
Medicine, General & Internal
Orla M. Fitzpatrick, Catherine Murphy, Erica Duignan, Keith Egan, Bryan T. Hennessy, Liam Grogan, Adrian Murphy, Oscar S. Breathnach, Jaruska Naidoo, Patrick G. Morris
Summary: This study compared the distances traveled and additional costs incurred by patients participating in clinical trials versus those receiving standard of care systemic anticancer therapy (SACT). The findings revealed that patients enrolled in clinical trials traveled significantly longer distances and incurred higher costs compared to those receiving standard SACT.
IRISH JOURNAL OF MEDICAL SCIENCE
(2022)
Article
Medicine, General & Internal
Anna Linehan, Orla Fitzpatrick, Darren Cowzer, Maeve A. Hennessy, Zac L. Coyne, Amy Nolan, Maeve Clarke, Roisin Ni Dhonaill, Bryan T. Hennessy, Patrick G. Morris, Liam Grogan, Oscar Breathnach
Summary: The COVID-19 pandemic has had a significant impact on healthcare globally, with higher incidence and worse outcomes reported in cancer patients. A study at Beaumont Hospital found that patients with lung cancer had higher rates of COVID-19 and poorer outcomes. Factors associated with higher mortality included advanced cancer, poorer performance status, and higher Palliative Prognostic Score.
IRISH JOURNAL OF MEDICAL SCIENCE
(2022)
Article
Oncology
Mattia Cremona, Cassandra J. Vandenberg, Angela M. Farrelly, Stephen F. Madden, Clare Morgan, Roshni Kalachand, Jessica N. McAlpine, Sinead Toomey, David G. Huntsman, Liam Grogan, Oscar Breathnach, Patrick Morris, Mark S. Carey, Clare L. Scott, Bryan T. Hennessy
Summary: The study found that XIAP protein expression is increased in BRCA1-mutated cancers, associated with optimization of PARP and NF-kB activation. BRCA1-mutated cells are more sensitive to IAP inhibitors, and treatment with IAP inhibitors can restore the efficacy of PARP inhibitors.
BRITISH JOURNAL OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Donatella Romaniello, Valerio Gelfo, Federica Pagano, Enea Ferlizza, Michela Sgarzi, Martina Mazzeschi, Alessandra Morselli, Carmen Miano, Gabriele D'Uva, Mattia Lauriola
Summary: This study found that IL-1 mediates the mechanism of CTX resistance in mCRC. Sensitive CRC cells showed senescence and G0 phase arrest under CTX treatment, while CTX-resistant cells maintained high expression of IL-1R1 and experienced post-senescence reprogramming. Treating CTX-resistant cells with a recombinant decoy could push them back into senescence and block their proliferation.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2022)
Article
Oncology
Daniel J. Ryan, Sinead Toomey, Robert Smyth, Stephen F. Madden, Julie Workman, Robert Cummins, Katherine Sheehan, Joanna Fay, Jarushka Naidoo, Oscar S. Breathnach, Patrick G. Morris, Liam Grogan, Michael E. O'Brien, Imran Sulaiman, Bryan T. Hennessy, Ross K. Morgan
Summary: Small diagnostic tissue samples may not be sufficient to detect oncogenic driver mutations in lung cancer, while liquid biopsies may provide better reflection of tumor heterogeneity. This study found that compared to tissue NGS, both plasma and exhaled breath condensate (EBC) identified a higher number of mutations, and there were differences in mutation profiles between plasma and EBC.
Article
Oncology
Seamus O'Reilly, Verena Murphy, Eibhlin Mulroe, Lisa Tucker, Fiona Carragher, Jacinta Marron, Aoife M. Shannon, Ken Rogan, Roisin M. Connolly, Bryan T. Hennessy, Ray S. McDermott
Summary: This study analyzed the impact of the COVID-19 pandemic on cancer clinical trials in Ireland. Clinical trial accrual decreased by 54%, with radiotherapy trials being the most affected. This reduction was due to reduced staffing, delays in trial logistics, and safety concerns. Remote monitoring and visits became more common.
Article
Oncology
Carmen Miano, Alessandra Morselli, Francesca Pontis, Chiara Bongiovanni, Francesca Sacchi, Silvia Da Pra, Donatella Romaniello, Riccardo Tassinari, Michela Sgarzi, Elvira Pantano, Carlo Ventura, Mattia Lauriola, Gabriele D'Uva
Summary: This study evaluated the role of ERBB3 in different molecular subtypes of breast cancer and found that higher ERBB3 levels are associated with shorter relapse-free survival in basal-like breast cancer patients. The NRG1/ERBB3/ERBB2 pathway was found to promote anchorage-independent growth of basal-like breast cancer cells. These findings suggest that targeting ERBB2 may be a potential therapeutic strategy for basal-like breast cancer.
Article
Oncology
Yvonne E. Smith, Guannan Wang, Ciara L. Flynn, Stephen F. Madden, Owen MacEneaney, Rodrigo G. B. Cruz, Cathy E. Richards, Hanne Jahns, Marian Brennan, Mattia Cremona, Bryan T. Hennessy, Katherine Sheehan, Alexander Casucci, Faizah A. Sani, Lance Hudson, Joanna Fay, Sri H. Vellanki, Siobhan O'Flaherty, Marc Devocelle, Arnold D. K. Hill, Kieran Brennan, Saraswati Sukumar, Ann M. Hopkins
Summary: Specific drug targets for breast ductal carcinoma in situ (DCIS) are difficult to determine, but this study suggests that JAM-A, a cell surface protein, could be a potential therapeutic target in DCIS patients. The study found that JAM-A is upregulated in DCIS patient tissues and a novel JAM-A-binding peptide inhibitor showed efficacy in inhibiting tumor growth in in vivo models. This finding provides valuable insights for the development of novel treatments for DCIS patients.
Review
Oncology
Enea Ferlizza, Donatella Romaniello, Francesco Borrelli, Federica Pagano, Cinzia Girone, Valerio Gelfo, Rikke Sofie Kuhre, Alessandra Morselli, Martina Mazzeschi, Michela Sgarzi, Daria Maria Filippini, Gabriele D'Uva, Mattia Lauriola
Summary: Extracellular vesicles (EVs), including microvesicles and exosomes, are important for intercellular communication by transporting proteins and nucleic acids. In solid cancers, the Epidermal Growth Factor Receptor (EGFR) plays a crucial role. EGFR is correlated with EVs production in EGFR-dependent solid tumors, leading to dissemination of EGFR and related molecules, promoting cell proliferation, modifying the tumor microenvironment, facilitating metastasis, and causing resistance to treatment. Liquid biopsy approaches have started using EGFR and EVs in EGFR-dependent tumor patients to evaluate their potential as biomarkers for diagnosing and monitoring tumor progression and therapy efficacy.
