Article
Hematology
Freda K. Stevenson, Francesco Forconi, Thomas J. Kipps
Summary: Research into chronic lymphocytic leukemia has led to significant improvements in the assessment and treatment of patients, with designer drugs now successfully targeting tumor cells based on their biology. Classifying CLL into unmutated (U) and mutated (M) diseases based on the mutational status of IGHV sequences reveals distinct origins, biology, and clinical behaviors for each. Despite advances, challenges such as cell-escape strategies and immunosuppression remain, necessitating continued research into CLL biology.
Review
Oncology
Andrew H. Lipsky, Nicole Lamanna
Summary: Targeted therapies have revolutionized the frontline treatment for CLL, reducing reliance on chemoimmunotherapy. Drugs such as ibrutinib, acalabrutinib, and venetoclax have shown efficacy in oral therapy. This review explores novel therapeutic strategies using these agents in combination, highlighting the importance of patient characteristics and study methodology.
Review
Hematology
Sigrid S. Skanland, Anthony R. Mato
Summary: Insight into the mechanisms of resistance to targeted therapies in chronic lymphocytic leukemia (CLL) has led to the development of strategies to prevent and overcome resistance, including combination therapies targeting bypass mechanisms, temporally sequencing of therapies, improved clinical trial designs, and real-time monitoring of patient response. These approaches aim to secure effective treatment options at the relapsed setting and overcome acquired resistance to existing therapies.
Article
Pharmacology & Pharmacy
Fanny Gallais, Loic Ysebaert, Fabien Despas, Sandra De Barros, Lucie Oberic, Ben Allal, Etienne Chatelut, Melanie White-Koning
Summary: This study developed the first PK-PD model for ALC in patients with CLL under ibrutinib treatment. The results of the model suggested that estimated lymphocyte counts in tissues and blood could be used as an early predictor of treatment response in CLL patients.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Hematology
Vaclav Seda, Eva Vojackova, Laura Ondrisova, Lenka Kostalova, Sonali Sharma, Tomas Loja, Gabriela Mladonicka Pavlasova, Daniel Zicha, Marie Kudlickova Peskova, Jan Krivanek, Kvetoslava Liskova, Leos Kren, Vladimir Benes, Katerina Musilova Litzmanova, Marek Borsky, Jan Oppelt, Jan Verner, Sarka Pospisilova, Yvona Brychtova, Anna Panovska, Zhi Tan, Shuxing Zhang, Michael Doubek, Katerina Amruz Cerna, Jiri Mayer, Marek Mraz
Summary: The migration and survival of CLL cells are influenced by GAB1, which can be targeted for therapeutic purposes, especially in combination with BTK inhibitors.
Article
Medicine, General & Internal
J. R. Brown, B. Eichhorst, P. Hillmen, W. Jurczak, M. Kazmierczak, N. Lamanna, S. M. O'Brien, C. S. Tam, L. Qiu, K. Zhou, M. Simkovic, J. Mayer, A. Gillespie-Twardy, A. Ferrajoli, P. S. Ganly, R. Weinkove, S. Grosicki, A. Mital, T. Robak, A. Osterborg, H. A. Yimer, T. Salmi, M. -D. -Y. Wang, L. Fu, J. Li, K. Wu, A. Cohen, M. Shadman
Summary: In a multinational phase 3 trial, zanubrutinib was found to be superior to ibrutinib in treating relapsed or refractory CLL or SLL, with better efficacy and fewer side effects.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Review
Biotechnology & Applied Microbiology
Candida Vitale, Jamie Lynn Gibbons, Alessandra Ferrajoli
Summary: In the treatment of chronic lymphocytic leukemia (CLL), newer, more selective BTK inhibitors such as acalabrutinib are gaining interest due to their potential to reduce off-target effects of the drug, thereby minimizing side effects and treatment interruptions. This emerging therapy option has shown promise in clinical trials for both relapsed/refractory and treatment-naive CLL patients.
ONCOTARGETS AND THERAPY
(2021)
Review
Oncology
Julio Delgado, Filip Josephson, Jorge Camarero, Blanca Garcia-Ochoa, Lucia Lopez-Anglada, Carolina Prieto-Fernandez, Paula B. van Hennik, Irene Papadouli, Christian Gisselbrecht, Harald Enzmann, Francesco Pignatti
Summary: Acalabrutinib was approved in the European Union for the treatment of adult patients with chronic lymphocytic leukemia who have not received treatment before or whose disease did not respond to previous therapy. It showed a significant improvement in progression-free survival compared to standard therapy, with an acceptable safety profile and positive benefit-risk ratio.
Article
Biochemistry & Molecular Biology
Andrea Rizzuto, Angelo Pirrera, Emilia Gigliotta, Salvatrice Mancuso, Candida Vullo, Giulia Maria Camarda, Cristina Rotolo, Arianna Roppolo, Corinne Spoto, Massimo Gentile, Cirino Botta, Sergio Siragusa
Summary: The current treatment for chronic lymphocytic leukemia (CLL) relies on chemotherapy, immunotherapy, and targeted inhibitors. However, the multitude of choices and lack of direct comparisons make treatment selection challenging. To address this, a systematic review and meta-analysis of clinical trials in CLL were performed. The results showed that a combination of obinutuzumab with acalabrutinib was the most effective treatment, especially in the absence of del17/P53 mutations. Additionally, chemotherapy is becoming less relevant in the first-line treatment of CLL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Maria Josefina Quezada, Pablo Lopez-Bergami
Summary: ROR1 is a receptor for WNT5A and related Wnt proteins, which regulates cell migration, cell polarity, neural patterning, and organogenesis during embryonic development. It transduces signals from Wnt glycoproteins to intracellular Wnt/PCP and Wnt/Ca++ pathways. In addition, it activates multiple signaling pathways in cancer cells, such as PI3K/AKT, MAPK, NF-Kappa B, STAT3, and Hippo pathways. Aberrant expression of ROR1 in cancer is associated with tumor progression and poor survival, making it a potential therapeutic target.
CELLULAR SIGNALLING
(2023)
Article
Pharmacology & Pharmacy
Vi Lam, Scott Best, Adam Kittai, Kirsten Orand, Stephen E. Spurgeon, Tingting Liu, Alexey V. Danilov
Summary: A phase 2 clinical trial found that combination therapy of SYK inhibitor entospletinib and anti-CD20 antibody obinutuzumab in CLL patients led to rapid downmodulation of activated proteins and anti-apoptotic proteins in CLL cells, partially restoring T-cell immunity.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Oncology
Peter Hillmen, Barbara Eichhorst, Jennifer R. Brown, Nicole Lamanna, Susan M. O'Brien, Constantine S. Tam, Lugui Qiu, Maciej Kazmierczak, Keshu Zhou, Martin Simkovic, Jiri Mayer, Amanda Gillespie-Twardy, Mazyar Shadman, Alessandra Ferrajoli, Peter S. Ganly, Robert Weinkove, Sebastian Grosicki, Andrzej Mital, Tadeusz Robak, Anders Osterborg, Habte A. Yimer, Tommi Salmi, Meng Ji, Jessica Yecies, Adam Idoine, Kenneth Wu, Jane Huang, Wojciech Jurczak
Summary: The study compared the efficacy and safety of zanubrutinib and ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia. The results showed that zanubrutinib had better outcomes in terms of efficacy, atrial fibrillation rate, and cardiac safety compared to ibrutinib.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Pharmacology & Pharmacy
Gustavo P. Amarante-Mendes, Aamir Rana, Tarcila Santos Datoguia, Nelson Hamerschlak, Gabriela Brumatti
Summary: The constitutively active BCR-ABL1 tyrosine kinase plays a role in leukemia and initiates a complex signaling transduction cascade. Tyrosine kinase inhibitors have revolutionized the treatment of CML, but complete cure is not achieved. Other mechanisms exist in the later stages of the disease.
Article
Rheumatology
Mitsuhiro Akiyama, Keiko Yoshimoto, Sho Ishigaki, Katsuya Suzuki, Tsutomu Takeuchi, Yuko Kaneko
Summary: CD29(+)IL-17RA(+) T effector cells are increased in SpA and correlated with disease activity. Anti-IL-17 monoclonal antibodies may be effective by reducing this pathogenic T cell population.
Article
Oncology
Maria Edilova, Jaclyn C. Law, Safoura Zangiabadi, Kenneth Ting, Achire N. Mbanwi, Andrea Arruda, David Uehling, Methvin Isaac, Michael Prakesch, Rima Al-awar, Mark D. Minden, Ali A. Abdul-Sater, Tania H. Watts
Summary: The study shows that PKN1 plays a crucial role in CLL by protecting TRAF1, and inhibitors like OTSSP167 and XL-228 can induce CLL cell death by reducing TRAF1. These findings suggest the PKN1-TRAF1 signaling axis as a potential new target for CLL.
Article
Hematology
Matthew S. Zabriskie, Orlando Antelope, Anupam R. Verma, Lauren R. Draper, Christopher A. Eide, Anthony D. Pomicter, Thai Hoa Tran, Brian J. Druker, Jeffrey W. Tyner, Rodney R. Miles, James M. Graham, Jae-Yeon Hwang, Katherine E. Varley, Reha M. Toydemir, Michael W. Deininger, Elizabeth A. Raetz, Thomas O'Hare
Article
Oncology
Rebecca Mitchell, Lisa E. M. Hopcroft, Pablo Baquero, Elaine K. Allan, Kay Hewit, Daniel James, Graham Hamilton, Arunima Mukhopadhyay, Jim O'Prey, Alan Hair, Junia V. Melo, Edmond Chan, Kevin M. Ryan, Veronique Maguer-Satta, Brian J. Druker, Richard E. Clark, Subir Mitra, Pawel Herzyk, Franck E. Nicolini, Paolo Salomoni, Emma Shanks, Bruno Calabretta, Tessa L. Holyoake, G. Vignir Helgason
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2018)
Article
Hematology
Matthew S. Zabriskie, Orlando Antelope, Anupam R. Verma, Lauren R. Draper, Christopher A. Eide, Anthony D. Pomicter, Thai Hoa Tran, Brian J. Druker, Jeffrey W. Tyner, Rodney R. Miles, James M. Graham, Jae-Yeon Hwang, Katherine E. Varley, Reha M. Toydemir, Michael W. Deininger, Elizabeth A. Raetz, Thomas O'Hare
Article
Oncology
Rebecca Mitchell, Lisa E. M. Hopcroft, Pablo Baquero, Elaine K. Allan, Kay Hewit, Daniel James, Graham Hamilton, Arunima Mukhopadhyay, Jim O'Prey, Alan Hair, Junia V. Melo, Edmond Chan, Kevin M. Ryan, Veronique Maguer-Satta, Brian J. Druker, Richard E. Clark, Subir Mitra, Pawel Herzyk, Franck E. Nicolini, Paolo Salomoni, Emma Shanks, Bruno Calabretta, Tessa L. Holyoake, G. Vignir Helgason
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2018)
Letter
Hematology
Kevin Watanabe-Smith, Brian J. Druker, Jeffrey W. Tyner, David K. Edwards
Review
Oncology
Ellin Berman, Brian J. Druker, Richard Burwick
JOURNAL OF CLINICAL ONCOLOGY
(2018)
Letter
Oncology
Ellin Berman, Brian J. Druker, Richard Burwick
JOURNAL OF CLINICAL ONCOLOGY
(2018)
Article
Oncology
Mona M. Hosseini, Stephen E. Kurtz, Sherif Abdelhamed, Shawn Mahmood, Monika A. Davare, Andy Kaempf, Johannes Elferich, Jason E. McDermott, Tao Liu, Samuel H. Payne, Ujwal Shinde, Karin D. Rodland, Motomi Mori, Brian J. Druker, Jack W. Singer, Anupriya Agarwal
Article
Cell Biology
Joao Agostinho Machado-Neto, Bruna Alves Fenerich, Renata Scopim-Ribeiro, Christopher A. Eide, Juan Luiz Coelho-Silva, Carlos Roberto Porto Dechandt, Jaqueline Cristina Fernandes, Ana Paula Nunes Rodrigues Alves, Priscila Santos Scheucher, Belinda Pinto Simoes, Luciane Carla Alberici, Lorena Lobo de Figueiredo Pontes, Cristina E. Tognon, Brian J. Druker, Eduardo Magalhaes Rego, Fabiola Traina
CELL DEATH & DISEASE
(2018)
Article
Oncology
Stephen E. Kurtz, Christopher A. Eide, Andy Kaempf, Motomi Mori, Cristina E. Tognon, Uma Borate, Brian J. Druker, Jeffrey W. Tyner
Letter
Oncology
Ellin Berman, Brian J. Druker, Richard Burwick
JOURNAL OF CLINICAL ONCOLOGY
(2019)
Article
Multidisciplinary Sciences
Haijiao Zhang, Samantha Savage, Anna Reister Schultz, Daniel Bottomly, Libbey White, Erik Segerdell, Beth Wilmot, Shannon K. McWeeney, Christopher A. Eide, Tamilla Nechiporuk, Amy Carlos, Rachel Henson, Chenwei Lin, Robert Searles, Hoang Ho, Yee Ling Lam, Richard Sweat, Courtney Follit, Vinay Jain, Evan Lind, Gautam Borthakur, Guillermo Garcia-Manero, Farhad Ravandi, Hagop M. Kantarjian, Jorge Cortes, Robert Collins, Daelynn R. Buelow, Sharyn D. Baker, Brian J. Druker, Jeffrey W. Tyner
NATURE COMMUNICATIONS
(2019)
Article
Oncology
Leylah M. Drusbosky, Robinson Vidva, Saji Gera, Anjanasree Lakshminarayana, Vijayashree P. Shyamasundar, Ashish Kumar Agrawal, Anay Talawdekar, Taher Abbasi, Shireen Vali, Cristina E. Tognon, Stephen E. Kurtz, Jeffrey W. Tyner, Shannon K. McWeeney, Brian J. Druker, Christopher R. Cogle
Article
Biology
Nathalie Javidi-Sharifi, Jacqueline Martinez, Isabel English, Sunil K. Joshi, Renata Scopim-Ribiero, David K. Edwards, Anupriya Agarwal, Claudia Lopez, Danielle Jorgens, Jeffrey W. Tyner, Brian J. Druker, Elie Traer
Article
Oncology
Monika A. Davare, Jacob J. Henderson, Anupriya Agarwal, Jacob P. Wagner, Sudarshan R. Iyer, Nameeta Shah, Randy Woltjer, Romel Somwar, Stephen W. Gilheeney, Ana DeCarvalo, Tom Mikkelson, Erwin G. Van Meir, Marc Ladanyi, Brian J. Druker
CLINICAL CANCER RESEARCH
(2018)