Article
Oncology
David Howard, David James, Jezabel Garcia-Parra, Belen Pan-Castillo, Jenny Worthington, Nicole Williams, Zoe Coombes, Sophie Colleen Rees, Kerryn Lutchman-Singh, Lewis W. Francis, Paul Rees, Lavinia Margarit, R. Steven Conlan, Deyarina Gonzalez
Summary: Ovarian cancer is a deadly disease that is often diagnosed late, resulting in poor prognosis. Platinum-based therapies are commonly used, but resistance to these treatments is common, making prognosis even worse. This study aimed to evaluate the effectiveness of CDK inhibitors in platinum-resistant ovarian cancer models and their potential clinical utility. The results showed that the CDK inhibitor, dinaciclib, was highly effective in both cell lines and primary cells of ovarian cancer, even more so than cisplatin. Furthermore, resistance to cisplatin did not affect the sensitivity to dinaciclib, and the two drugs had an additive effect when used together. This suggests a potential role for pan-CDK inhibitors in the treatment of advanced and platinum-resistant ovarian cancer.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
David Howard, David James, Kate Murphy, Jezabel Garcia-Parra, Belen Pan-Castillo, Stuart Rex, Annemarie Moul, Eilir Jones, Marc Bilbao-Asensio, Saul Michue-Seijas, Kerryn Lutchman-Singh, Lavinia Margarit, Lewis W. Francis, Paul Rees, Deyarina Gonzalez, R. Steven Conlan
Summary: Endometrial cancer (EC) is the sixth most common cancer in women globally, with a 5-year survival rate below 50% for advanced stage diagnoses. Novel therapies are needed to improve patient outcomes, and pan-cyclin-dependent kinase inhibitors like dinaciclib show potential for effective treatment of EC.
Review
Cell Biology
Aleksandra J. Pluta, Cecilia Studniarek, Shona Murphy, Chris J. Norbury
Summary: This article discusses the important roles of structurally related cyclin-dependent protein kinases (CDKs) in eukaryotic cell function, highlighting their roles in cell cycle regulation and transcriptional regulation, and the overlap between these processes.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2023)
Review
Biochemistry & Molecular Biology
Pawel Lukasik, Irena Baranowska-Bosiacka, Katarzyna Kulczycka, Izabela Gutowska
Summary: Recent studies have shown that small molecule drugs targeting CDK inhibitors have become attractive options for treating cancer and neurodegenerative disorders. Most CDK inhibitors target the ATP binding pocket, but the similarity in structure among CDK kinases makes achieving selectivity challenging. Therefore, inhibitors binding outside the ATP binding site have attracted great interest for their potential applications in the biomedical field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Mitra Zabihi, Ramin Lotfi, Amir-Mohammad Yousefi, Davood Bashash
Summary: CDKs, cyclins, and CKIs play important roles in the cell cycle regulatory machinery, and dysregulation of their expression or function can contribute to tumorigenesis. While designing CDK inhibitors to target tumor cells shows promise, the non-canonical functions of CDKs pose challenges in their application. This review aims to explore the biology of CDKs and their contribution to tumorigenesis, and discuss the pros and cons of CDK inhibition in the treatment of human cancers.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Lanlan Fu, Jiajia Mou, Yanru Deng, Xiaoliang Ren, Shuang Qiu
Summary: CDK1 plays an essential role in the cell cycle and has emerged as a new target for cancer therapy. A new series of flavone derivatives, including compound 2a, were discovered as potent CDK1 inhibitors. Compound 2a exhibited strong inhibitory activity against CDK1 and showed potential as a lead compound for CDK1 inhibitor development.
FRONTIERS IN CHEMISTRY
(2022)
Review
Oncology
Soudeh Ghafouri-Fard, Tayyebeh Khoshbakht, Bashdar Mahmud Hussen, Peixin Dong, Nikolaus Gassler, Mohammad Taheri, Aria Baniahmad, Nader Akbari Dilmaghani
Summary: This article summarizes the important role of Cyclin-dependent kinases (CDK) in cancer, emphasizing the significance of understanding CDK function and mechanisms for future cancer therapies targeting these kinases.
CANCER CELL INTERNATIONAL
(2022)
Review
Cell Biology
Yi Xiao, Jixin Dong
Summary: This article discusses the role and therapeutic potential of Cyclin K in cancer. Studies have shown that Cyclin K plays important roles in various biological processes and is critical in cancer cell growth and therapeutic resistance. Additionally, the druggability of Cyclin K has been demonstrated, providing novel opportunities for cancer treatment.
Editorial Material
Chemistry, Medicinal
Mark Klein
Summary: Cyclin-dependent kinases (CDKs) have important roles in normal cells and can be targeted for cancer therapy. CDK4 inhibitors have been approved for advanced breast cancer treatment. However, the development of selective inhibitors for individual CDKs is challenging due to the highly conserved ATP-binding site.
Article
Biochemistry & Molecular Biology
Wenjun Gui, Yumo Hang, Wang Cheng, Minqi Gao, Jiaquan Wu, Zhuqing Ouyang
Summary: Cell cycle transitions are regulated by CDKs, with CDK3 playing a crucial role in the transitions of G0 to G1 and G1 to S phase. The crystal structure of CDK3 in complex with cyclin E1 has been determined, revealing similarities with CDK2 and insights into substrate specificity. The CDK inhibitor dinaciclib shows potent and specific inhibition of CDK3-cyclin E1, and the structure of this complex provides insights into its inhibitory mechanism. These findings advance our understanding of CDK3 activation and lay a foundation for drug design.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Cell Biology
Luke J. Nelson, Kyleen E. Castro, Binzhi Xu, Junyi Li, Nguyen B. Dinh, Jordan M. Thompson, Jordan Woytash, Kevin R. Kipp, Olga Razorenova
Summary: The cyclin-dependent kinase inhibitor, Dinaciclib, shows potential as a new targeted therapeutic for clear cell renal cell carcinoma (CC-RCC). In vitro and in vivo experiments demonstrate that Dinaciclib inhibits cell proliferation, induces apoptosis, and suppresses tumor growth in a mouse model. It can target both cancer stem cells and non-cancer stem cells. The therapeutic effect of Dinaciclib is enhanced by the loss of the VHL tumor suppressor gene.
Article
Biochemistry & Molecular Biology
Jiajia Mou, Shuang Qiu, Danghui Chen, Yanru Deng, Teka Tekleab
Summary: The study reported a series of baicalein derivatives that significantly inhibited the proliferation of MCF-7 tumor cells and the activity of CDK1/cyclin B kinase. Among them, compound 4a showed better inhibition against MCF-7 proliferation, while compound 3o exhibited the best activity against CDK1/cyclin B kinase. These findings demonstrate that baicalein derivatives can be used as CDK1 inhibitors fighting against cancer.
CHEMICAL BIOLOGY & DRUG DESIGN
(2021)
Article
Biochemistry & Molecular Biology
Mateusz Kciuk, Adrianna Gieleci, Somdutt Mujwar, Mariusz Mojzych, Renata Kontek
Summary: The cyclin-dependent kinase (CDK) family plays a critical role in regulating transcription and cell-cycle progression. Recent studies have revealed their involvement in DNA damage response (DDR) and repair, impacting the fidelity of cell division and maintenance of genomic integrity.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Oncology
Emanuel Raschi, Michele Fusaroli, Andrea Ardizzoni, Elisabetta Poluzzi, Fabrizio De Ponti
Summary: This post-marketing research studied the role of cyclin-dependent kinase 4/6 inhibitors in cancer-associated thrombosis, finding a potential class effect for venous thrombosis and distinctive arterial events for ribociclib. The study suggests proactive monitoring by oncologists for thromboembolic events with CDK4/6 inhibitors and supports pharmacovigilance for safe prescribing in oncology.
Review
Biochemistry & Molecular Biology
Mateusz Kciuk, Adrianna Gielecinska, Somdutt Mujwar, Mariusz Mojzych, Renata Kontek
Summary: Synthetic lethal interactions involving CDKs with MYC, PARP-1, and TP53 are emerging as potential targets for selectively targeting tumor cells with DNA repair defects. These interactions reveal the crucial roles of cell cycle regulatory proteins in the DNA damage response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Hematology
Yago Nieto, Stephen Gruschkus, Benigno C. Valdez, Roy B. Jones, Paolo Anderlini, Chitra Hosing, Uday Popat, Muzaffar Qazilbash, Partow Kebriaei, Amin Alousi, Neeraj Saini, Samer Srour, Katayoun Rezvani, Jeremy Ramdial, Melissa Barnett, Alison Gulbis, Terri Lynn Shigle, Sairah Ahmed, Swaminathan Iyer, Hun Lee, Ranjit Nair, Simrit Parmar, Raphael Steiner, Bouthaina Dabaja, Chelsea Pinnix, Jillian Gunther, Branko Cuglievan, Kris Mahadeo, Sajad Khazal, Hubert Chuang, Richard Champlin, Elizabeth J. Shpall, Borje S. Andersson
Summary: The post-HDC/ASCT outcomes of patients with high-risk relapsed classical Hodgkin lymphoma have improved over the last 15 years. Prior treatment with brentuximab vedotin and optimized synergistic chemotherapy were associated with more favorable outcomes.
Article
Ophthalmology
Srinivasan Sanjay, Seo Wei Leo, Kah - Guan Au Eong, Gitalisa Andayani Adriono, Kenneth C. S. Fong, Kartik Anand, Rumita S. Kadarisman, David B. Granet, Padmamalini Mahendradas, Rohit Shetty, Sharon D. Souza, Swaminathan P. Iyer
Summary: Global ophthalmologists have experienced significant changes in practice patterns during the COVID-19 pandemic, with a precipitous drop in surgical procedures. 41% of ophthalmologists are considering resuming elective surgeries after evaluating the situation. More than 2/3 of respondents prioritize physical distancing, mask-wearing, and hand disinfection for patient protection.
OPHTHALMIC EPIDEMIOLOGY
(2022)
Article
Hematology
Mridula Krishnan, R. Gregory Bociek, Michelle Fanale, Swaminathan P. Iyer, Mary Jo Lechowicz, Philip J. Bierman, James O. Armitage, Matthew Lunning, Avyakta Kallam, Julie M. Vose
Summary: The phase 1 study of carfilzomib in patients with Peripheral T-cell lymphomas showed that the drug was reasonably tolerated, but had a limited response rate and short duration of response, indicating a lack of promise for carfilzomib as a single agent in this patient population.
ANNALS OF HEMATOLOGY
(2022)
Article
Hematology
Adi Zoref-Lorenz, Jun Murakami, Liron Hofstetter, Swaminathan Iyer, Ahmad S. Alotaibi, Shehab Fareed Mohamed, Peter G. Miller, Elad Guber, Shiri Weinstein, Joanne Yacobovich, Sarah Nikiforow, Benjamin L. Ebert, Adam Lane, Oren Pasvolsky, Pia Raanani, Arnon Nagler, Nancy Berliner, Naval Daver, Martin Ellis, Michael B. Jordan
Summary: This study found that the optimized HLH inflammatory (OHI) index, which combines levels of soluble CD25 and ferritin, can effectively diagnose HLH and predict mortality in patients with HMs. Additionally, the index can identify high-risk patients who may not be diagnosed with HLH according to traditional criteria.
Article
Oncology
Jason Westin, R. Eric Davis, Lei Feng, Fredrick Hagemeister, Raphael Steiner, Hun Ju Lee, Luis Fayad, Loretta Nastoupil, Sairah Ahmed, Alma Rodriguez, Michelle Fanale, Felipe Samaniego, Swaminathan P. Iyer, Ranjit Nair, Yasuhiro Oki, Nathan Fowler, Michael Wang, Man Chun John Ma, Francisco Vega, Timothy McDonnell, Chelsea Pinnix, Donna Griffith, Yang Lu, Sanjit Tewari, Ryan Sun, David W. Scott, Christopher R. Flowers, Sattva Neelapu, Michael R. Green
Summary: This study introduces a new treatment strategy (RLI) for newly diagnosed DLBCL patients, which combines targeted therapy with drugs before chemotherapy. The results showed high treatment response rates and durable responses in DLBCL patients treated with RLI. This establishes the potential for developing biologically driven and noncytotoxic first-line therapies for DLBCL.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Pathology
Karen A. Nahmod, Beenu Thakral, F. N. U. Aakash, Swaminathan P. Iyer, L. Jeffrey Medeiros, Andres E. Quesada
Summary: T-prolymphocytic leukemia (T-PLL) is a rare and aggressive T-cell leukemia that is characterized by marked peripheral blood lymphocytosis. Some patients initially present with moderate and stable lymphocytosis, but eventually develop marked lymphocytosis and rapidly progressive disease.
ANNALS OF DIAGNOSTIC PATHOLOGY
(2023)
Editorial Material
Hematology
Swaminathan P. Iyer
Summary: In this study, the authors investigated the relationship between T-cell acute lymphoblastic leukemia (T-ALL) and endothelial cells (ECs), suggesting that the tumor microenvironment (TME), particularly ECs, may impact drug responses.
Article
Hematology
Lianqun Qiu, Guilin Tang, Shaoying Li, Francisco Vega, Pei Lin, Sa A. Wang, Wei Wang, Swaminathan P. Iyer, Luis Malpica, Roberto N. Miranda, Sergej Konoplev, Zhenya Tang, Hong Fang, L. Jeffrey Medeiros, Jie Xu
Summary: DUSP22 rearrangement is associated with systemic ALK-negative ALCL but recent study found that it is not associated with better clinical outcome. This study compared the clinicopathological features and outcomes of patients with ALK-negative ALCL with DUSP22 rearrangement (n=22) versus those without DUSP22 rearrangement (n=59). The survival rate of patients with DUSP22 rearrangement was not significantly different from those without DUSP22 rearrangement.
Letter
Hematology
Andrew P. Jallouk, Sushanth Gouni, Jason Westin, Lei Feng, Haleigh Mistry, Raphael E. Steiner, Jinsu James, Mansoor Noorani, Sandra Horowitz, Nahum Puebla-Osorio, Luis E. Fayad, Swaminathan P. Iyer, Misha Hawkins, Christopher R. Flowers, Sairah Ahmed, Loretta J. Nastoupil, Partow Kebriaei, Elizabeth J. Shpall, Sattva S. Neelapu, Yago Nieto, Paolo Strati
Article
Biophysics
Taha Al-Juhaishi, Yingjun Wang, Denai R. Milton, Zijun Y. Xu-Monette, Elias Jabbour, May Daher, Jin S. Im, Qaiser Bashir, Swaminathan P. Iyer, David Marin, Amanda L. Olson, Uday Popat, Muzaffar Qazilbash, Gabriela Rondon, Alison M. Gulbis, Richard E. Champlin, Ken H. Young, Issa F. Khouri
Summary: Dual expression of MYC and BCL2 proteins (DEL) and cell of origin (COO) are important prognostic factors in DLBCL patients after chemotherapy. The study found that DEL/DHL had worse overall survival compared to DEL/non-DHL, and DEL/DHL, age >60 years, and >2 prior therapies were important prognostic factors for overall survival on multivariable analysis. The impact of COO on prognosis was not significant.
BONE MARROW TRANSPLANTATION
(2023)
Article
Oncology
Christopher N. Nguyen, Swaminathan P. Iyer, Madeleine Duvic, Prajak J. Barde, Ajit Nair, Kasi Viswanath Routhu, Auris O. Huen
Summary: Mycosis fungoides (MF) and Sezary Syndrome (SS) are common subtypes of cutaneous T cell lymphomas (CTCL). Advanced-stage MF/SS have poor prognoses and may not respond to multiple systemic treatments. In this case, Tenalisib, an inhibitor of the phosphatidylinositol 3-kinase (PI3K) pathway, was used in combination with Romidepsin to achieve complete remission in a relapsed/refractory SS patient, and long-term remission was maintained with Tenalisib monotherapy.
INVESTIGATIONAL NEW DRUGS
(2023)
Article
Oncology
Max J. Gordon, Zhigang Duan, Hui Zhao, Loretta Nastoupil, Samuel Ng, Alexey V. Danilov, Swaminathan Iyer, Sharon H. Giordano
Summary: In this population-based study, we found that the frontline treatment regimen is associated with overall survival in older patients with peripheral T-cell lymphoma (PTCL), while the second-line treatment regimen has no impact on overall survival. CHOEP treatment regimen is independently associated with improved overall survival in patients without comorbidities.
LEUKEMIA & LYMPHOMA
(2023)
Letter
Hematology
Paolo Strati, Andrew Jallouk, Qing Deng, Xubin Li, Lei Feng, Ryan Sun, Sherry Adkins, Swapna Johncy, Taylor Cain, Raphael E. Steiner, Sairah Ahmed, Dai Chihara, Luis E. Fayad, Swaminathan P. Iyer, Sandra Horowitz, Loretta J. Nastoupil, Ranjit Nair, Ahmed Hassan, Taher E. Daoud, Misha Hawkins, Maria A. Rodriguez, Elizabeth J. Shpall, Jeremy L. Ramdial, Partow Kebriaei, David S. Hong, Jason R. Westin, Sattva S. Neelapu, Michael R. Green
Correction
Pathology
L. Jeffrey Medeiros, Mario L. Marques-Piubelli, Valentina F. I. Sangiorgio, Roberto Ruiz-Cordero, Francisco Vega, Andrew L. Feldman, Jennifer R. Chapman, Mark W. Clemens, Kelly K. Hunt, Mark G. Evans, Christine Khoo, Stephen Lade, Mark Silberman, Jerzy Morkowski, Edward M. Pina, Daniel C. Mills, Christopher M. Bates, Winston B. Magno, Aliyah R. Sohani, Beth A. Sieling, Joseph M. O'Donoghue, Chris M. Bacon, Neill Patani, Despina Televantou, Suzanne D. Turner, Laura Johnson, Fiona Macneill, Andrew C. Wotherspoon, Swaminathan P. Iyer, Luis E. Malpica, Keyur P. Patel, Jie Xu, Roberto N. Miranda
Article
Oncology
Guangchun Han, Qing Deng, Mario L. Marques-Piubelli, Enyu Dai, Minghao Dang, Man Chun John Ma, Xubin Li, Haopeng Yang, Jared Henderson, Olga Kudryashova, Mark Meerson, Sergey Isaev, Nikita Kotlov, Krystle J. Nomie, Alexander Bagaev, Edwin R. Parra, Luisa M. Solis Soto, Simrit Parmar, Fredrick B. Hagemeister, Sairah Ahmed, Swaminathan P. Iyer, Felipe Samaniego, Raphael Steiner, Luis Fayad, Hun Lee, Nathan H. Flower, Christopher R. Flowers, Paolo Strati, Jason R. Westin, Sattva S. Neelapu, Loretta J. Nastoupil, Francisco Vega, Linghua Wang, Michael R. Green
Summary: In this study, the tumor and immune cell populations of follicular lymphoma (FL) were characterized using single-cell RNA sequencing. Different subsets of T cells were identified, including cytotoxic CD4 T cells. Somatic mutations were found to be associated with reduced MHC expression on FL cells. The expression of MHCII genes by FL cells was correlated with significant differences in the proportions and immunophenotypic characteristics of T cells.
BLOOD CANCER DISCOVERY
(2022)