Review
Oncology
Cheng-Hao Chuang, Hsiao-Ling Chen, Hsiu-Mei Chang, Yu-Chen Tsai, Kuan-Li Wu, I-Hua Chen, Kung-Chao Chen, Jui-Ying Lee, Yong-Chieh Chang, Chin-Ling Chen, Yu-Kang Tu, Jen-Yu Hung, Chih-Jen Yang, Inn-Wen Chong
Summary: Anaplastic lymphoma kinase inhibitors have shown excellent efficacy in treating non-small cell lung cancer patients, with lorlatinib and low-dose alectinib performing well in first-line treatment. Different agents have varying advantages in terms of outcomes, highlighting the need for further large-scale phase III clinical trials to confirm conclusions.
Article
Oncology
Chuquan Shang, Bardes Hassan, Moinul Haque, Yuqi Song, Jing Li, Dongzhe Liu, Eva Lipke, Will Chen, Sylvie Giuriato, Raymond Lai
Summary: The study demonstrated that inhibiting autophagy in ALK + ALCL can increase drug sensitivity in stem-like cells, with differential Myc gene expression playing a critical role in this process. Stem-like cells have a greater impact on the efficacy of therapeutic drugs, indicating their crucial role in drug resistance.
Article
Multidisciplinary Sciences
Yoko Ota, Hiroyuki Yoda, Takahiro Inoue, Takayoshi Watanabe, Yoshinao Shinozaki, Atsushi Takatori, Hiroki Nagase
Summary: The study demonstrates the inhibitory effects of the newly developed ALK inhibitor CCC-003 on cell proliferation in ALK-mutated neuroblastoma, suggesting its potential for treating neuroblastoma and overcoming tyrosine kinase inhibitor resistance. CCC-003 preferentially binds to mutated DNA within the ALK gene and exerts anti-tumor activity through a distinct mode of action compared to other ALK inhibitors.
Article
Oncology
Mei-ting Chen, Xiao-hong Fu, He Huang, Zhao Wang, Xiao-jie Fang, Yu-Yi Yao, Quan-Guang Ren, Ze-geng Chen, Tong-yu Lin
Summary: The combination of crizotinib with chemotherapy may be effective in ALK-positive and crizotinib sensitive r/r sALCL patients, with significantly improved progression-free survival rates and overall survival rates within two years compared to the control group.
LEUKEMIA & LYMPHOMA
(2021)
Article
Hematology
Elif Karaca Atabay, Carmen Mecca, Qi Wang, Chiara Ambrogio, Ines Mota, Nina Prokoph, Giulia Mura, Cinzia Martinengo, Enrico Patrucco, Giulia Leonardi, Jessica Hossa, Achille Pich, Luca Mologni, Carlo Gambacorti-Passerini, Laurence Brugieres, Birgit Geoerger, Suzanne D. Turner, Claudia Voena, Taek-Chin Cheong, Roberto Chiarle
Summary: This study identified PTPN1 and PTPN2 phosphatases as drivers of resistance to ALK TKIs in ALK(+) ALCL. These phosphatases regulate ALK phosphorylation and activity, and their loss leads to TKI resistance. Furthermore, SHP2 is a key mediator of oncogenic ALK signaling, and PTPN1 acts as a phosphatase for SHP2. Combination therapy with a SHP2 inhibitor can overcome TKI resistance in ALK(+) ALCL.
Review
Medicine, General & Internal
L. B. Cameron, N. Hitchen, E. Chandran, T. Morris, R. Manser, B. J. Solomon, V Jordan
Summary: This study evaluated the safety and efficacy of ALK inhibitors as monotherapy for advanced ALK-rearranged NSCLC. The results showed that ALK inhibitors are effective in improving progression-free survival, overall survival, and overall response rate, with minimal adverse events compared to chemotherapy. Next-generation ALK inhibitors are more effective and safe than first-generation ALK inhibitors. However, further research is needed to compare different next-generation ALK inhibitors.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS
(2022)
Article
Oncology
V. Subbiahy, S. Kuraviy, S. Ganguly, D. R. Welch, C. J. Vivian, M. U. Mushtaq, A. Hegde, S. Iyer, A. Behrang, S. M. Ali, R. W. Madison, J. M. Venstrom, R. A. Jensen, J. P. McGuirk, H. M. Amin, R. Balusu
Summary: The study demonstrates that Ceritinib shows inhibitory effects on the fusion kinase NPM1-ALK and induces apoptosis of lymphoma cells in vitro and in vivo. Treatment with Ceritinib in the NPM1-ALKthorn ALCL xenograft model resulted in tumor regression and improved survival. Among 19,272 patients sequenced, 0.30% harbored ALK fusions, including various hematologic malignancies.
Article
Oncology
Laurence Brugieres, Nathalie Cozic, Roch Houot, Charlotte Rigaud, David Sibon, Julia Arfi-Rouche, Pierre Bories, Anne S. Cottereau, Alain Delmer, Stephane Ducassou, Nathalie Garnier, Laurence Lamant, Amaury Leruste, Frederic Millot, S. Moalla, Franck Morschhauser, Marie Nolla, Anne Pagnier, Yves Reguerre, Loic Renaud, Anne Schmitt, Mathieu Simonin, Arnaud Verschuur, Nathalie Hoog Labouret, Celine Mahier Ait Oukhatar, Gilles Vassal
Summary: The study examined the safety and efficacy of crizotinib in ALK-positive anaplastic large-cell lymphoma (ALK+ ALCL) patients, showing that crizotinib is effective in relapsed/refractory patients, but a large proportion experience relapse after discontinuation. Rating: 8/10.
EUROPEAN JOURNAL OF CANCER
(2023)
Review
Oncology
Yuan Wang, Jing He, Manyu Xu, Qingfeng Xue, Cindy Zhu, Juan Liu, Yaping Zhang, Wenyu Shi
Summary: This review provides an overview of research progress on ALK+ ALCL, including the study of drug resistance mechanisms and the application and development of new therapies. Potential treatment strategies are proposed to guide the design of future clinical trials.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Ting Zhao, Xiaowei Zhang, Xin Liu, Min Ren, Yufan Cheng, Jian Wang, Zhiguo Luo
Summary: This article describes a case in which a 57-year-old woman initially diagnosed with uterine leiomyosarcoma (LMS) was later re-diagnosed with uterine inflammatory myofibroblastic tumor (IMT) based on ALK expression and gene fusion. The patient achieved complete response and at least 18 months of progression-free survival after receiving ALK tyrosine kinase inhibitor (TKI) treatment.
FRONTIERS IN ONCOLOGY
(2023)
Article
Cell Biology
Pengfei Xu, Sujuan Xu, Haiyue Pan, Chencheng Dai, Yiran Xu, Luyao Wang, Yu Cong, Huilin Zhang, Jian Cao, Lili Ge, Xuemei Jia
Summary: Analyses of several databases showed that the lncRNA RNF157-AS1 is overexpressed in epithelial ovarian cancer tissues. Suppression or overexpression of RNF157-AS1 significantly affects the proliferation, invasion, and migration of EOC cells. RNF157-AS1 interacts with HMGA1 and EZH2 proteins, regulating the expression of ULK1 and DIRAS3 and influencing autophagy.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Yuxue Xia, Lu Zhang, Wenjuan He, Huaxiong Pan, Jun Fang, Guohui Cui
Summary: This study reported a case of ALK(+) LBCL in which the patient had progressive disease after treatment with crizotinib and chemotherapy, but achieved partial response and remained stable after treatment with alectinib combined with hyper-CVAD, followed by alectinib monotherapy.
CANCER BIOLOGY & THERAPY
(2023)
Review
Urology & Nephrology
Marco Bonilla, Kenar D. Jhaveri, Hassan Izzedine
Summary: This review introduces the main treatment method, ALK inhibitors, for NSCLC patients with ALK gene rearrangement or ROS1 oncogene fusion. However, the toxic side effects of these drugs, especially those related to the kidneys, need to be taken seriously.
CLINICAL KIDNEY JOURNAL
(2022)
Article
Oncology
Giulia Arosio, Geeta G. Sharma, Matteo Villa, Mario Mauri, Ilaria Crespiatico, Diletta Fontana, Chiara Manfroni, Cristina Mastini, Marina Zappa, Vera Magistroni, Monica Ceccon, Sara Redaelli, Luca Massimino, Anna Garbin, Federica Lovisa, Lara Mussolin, Rocco Piazza, Carlo Gambacorti-Passerini, Luca Mologni
Summary: Combining two drugs for the treatment of ALK+ ALCL can effectively prevent the emergence of resistant cells, showing superior efficacy compared to single drug treatments in controlling the expansion of lymphoma cells in the long term.
Article
Oncology
Giulia Mura, Elif Karaca Atabay, Matteo Menotti, Cinzia Martinengo, Chiara Ambrogio, Gloria Giacomello, Maddalena Arigoni, Martina Olivero, Raffaele A. Calogero, Roberto Chiarle, Claudia Voena
Summary: Anaplastic Large Cell Lymphoma (ALCL) is driven by the chimeric tyrosine kinase NPM-ALK, which downregulates the expression of CD45 via STAT3 and acts as a rheostat of ALK oncogenic signaling and resistance to TKI treatment. CD45 is a key regulator of T cell activation and cytokine responses through the JAK/STAT pathway. In ALK+ ALCL, NPM-ALK inhibits T cell molecules expression and activates surrogate TCR signaling. Inhibition of NPM-ALK kinase activity leads to increased expression of CD45RO isoform. Knocking-out CD45 results in increased resistance to ALK TKI treatment.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Dengxuan Fan, Hailing Yang, Weiqun Mao, Philip J. Rask, Lan Pang, Congjian Xu, Hariprasad Vankayalapat, Ahmed A. Ahmed, Robert C. Bast, Zhen Lu
Summary: The study reveals that ARN-3261 can enhance the efficacy of paclitaxel and carboplatin in treating ovarian cancer by increasing their ability to kill cancer cells and decreasing survivin levels. Further clinical evaluation of ARN-3261 is warranted based on these preclinical findings.
Article
Oncology
Johannes F. Fahrmann, Ehsan Irajizad, Makoto Kobayashi, Jody Vykoukal, Jennifer B. Dennison, Eunice Murage, Ranran Wu, James P. Long, Kim-Anh Do, Joseph Celestino, Karen H. Lu, Zhen Lu, Robert C. Bast, Samir Hanash
Summary: The study identified a plasma polyamine signature associated with ovarian cancer that complemented CA125 in detecting early-stage ovarian cancer, providing potential markers for improving sensitivity in ovarian cancer detection. Mass spectrometry quantified four polyamines in plasma samples from ovarian cancer cases and controls, with a polyamine signature showing improved sensitivity and capturing cases missed by CA125 alone. This MYC-driven plasma polyamine signature offers promise for enhancing early ovarian cancer detection.
Editorial Material
Oncology
Anna Lokshin, Robert C. Bast, Karin Rodland
Article
Medicine, Research & Experimental
Mara Artibani, Kenta Masuda, Zhiyuan Hu, Pascal C. Rauher, Garry Mallett, Nina Wietek, Matteo Morotti, Kay Chong, Mohammad KaramiNejadRanjbar, Christos E. Zois, Sunanda Dhar, Salma El-Sahhar, Leticia Campo, Sarah P. Blagden, Stephen Damato, Pubudu N. Pathiraja, Shibani Nicum, Fergus Gleeson, Alexandros Laios, Abdulkhaliq Alsaadi, Laura Santana Gonzalez, Takeshi Motohara, Ashwag Albukhari, Zhen Lu, Robert C. Bast, Adrian L. Harris, Christer S. Ejsing, Robin W. Klemm, Christopher Yau, Tatjana Sauka-Spengler, Ahmed Ashour Ahmed
Summary: In this study, researchers found that minimal residual disease (MRD) cells in ovarian cancer patients share important molecular signatures with tumor-initiating cells (TICs), while also exhibiting an adipocyte-like gene expression signature and undergoing epithelial-mesenchymal transition (EMT). Through a cell culture MRD model, it was discovered that MRD-mimic cells are dependent on fatty acid oxidation (FAO) for survival and resistance to cytotoxic agents. These findings suggest that EMT and FAO could be potential targets for eradicating MRD in ovarian cancer and support further testing of FAO inhibitors for MRD treatment.
Article
Oncology
Lijie Zhai, April Bell, Erik Ladomersky, Kristen L. Lauing, Lakshmi Bollu, Brenda Nguyen, Matthew Genet, Miri Kim, Peiwen Chen, Xinlei Mi, Jennifer D. Wu, Matthew J. Schipma, Brian Wray, John Griffiths, Richard D. Unwin, Simon J. Clark, Rajesh Acharya, Riyue Bao, Craig Horbinski, Rimas Lukas, Gary E. Schiltz, Derek A. Wainwright
Summary: This study reveals that nonenzymatic tumor cell IDO activity decreases survival and increases CFH and FHL-1 expression in human GBM independent of Trp metabolism. The increased intra-tumoral CFH and FHL-1 levels are associated with poorer survival in glioma patients. Like IDO effects, GBM cell FHL-1 expression increases intratumoral Treg and myeloid-derived suppressor cells while decreasing overall survival in mice with GBM, providing a new therapeutic target for GBM patients.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Chae Young Han, David A. Patten, Se Ik Kim, Jung Jin Lim, David W. Chan, Michelle K. Y. Siu, Youngjin Han, Euridice Carmona, Robin J. Parks, Cheol Lee, Li-Jun Di, Zhen Lu, Karen K. L. Chan, Ja-Lok Ku, Elizabeth A. Macdonald, Barbara C. Vanderhyden, Anne-Marie Mes-Masson, Hextan Y. S. Ngan, Annie N. Y. Cheung, Yong Sang Song, Robert C. Bast, Mary-Ellen Harper, Benjamin K. Tsang
Summary: This study highlights the functional interaction between HKII and activated P-p53 (Ser15) in the regulation of bioenergetics and chemosensitivity, emphasizing the increased nuclear HKII-P-p53 (Ser15) interaction as a potential prognostic biomarker in ovarian cancer.
Review
Oncology
Gamze Bildik, Xiaowen Liang, Margie N. Sutton, Robert C. Bast, Zhen Lu
Summary: DIRAS3 is an imprinted tumor suppressor gene that blocks RAS function, inhibits malignant transformation and cancer cell growth, and facilitates the survival of dormant cancer cells. Downregulation of DIRAS3 expression is associated with various cancers and can serve as a target for novel therapy after conventional treatment.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Oncology
Kristin L. M. Boylan, Ashley Petersen, Timothy K. Starr, Xuan Pu, Melissa A. Geller, Robert C. Bast, Karen H. Lu, Ugo Cavallaro, Denise C. Connolly, Kevin M. Elias, Daniel W. Cramer, Tanja Pejovic, Amy P. N. Skubitz
Summary: This study aimed to develop a multiprotein classifier for detecting early stages of ovarian cancer by analyzing the levels of 92 cancer-related proteins in the blood. The combination of four proteins successfully detected over 90% of women with ovarian cancer and improved sensitivity and specificity compared to using CA125 alone. These findings suggest potential new biomarkers for early stage ovarian cancer detection.
Article
Chemistry, Medicinal
Lakshmi R. Bollu, Prashant V. Bommi, Paige J. Monsen, Lijie Zhai, Kristen L. Lauing, April Bell, Miri Kim, Erik Ladomersky, Xinyu Yang, Leonidas C. Platanias, Daniela E. Matei, Marcelo G. Bonini, Hidayatullah G. Munshi, Rintaro Hashizume, Jennifer D. Wu, Bin Zhang, Charles David James, Peiwen Chen, Masha Kocherginsky, Craig Horbinski, Michael D. Cameron, Arabela A. Grigorescu, Bakhtiar Yamini, Rimas V. Lukas, Gary E. Schiltz, Derek A. Wainwright
Summary: This study developed a new compound that degrades the IDO1 protein and identified its therapeutic potential for glioblastoma patients.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Meeting Abstract
Oncology
Lijie Zhai, April Bell, Erik Ladomersky, Kristen Lauing, Lakshmi Bollu, Brenda Nuygen, Matthew Genet, Miri Kim, Xinlei Mi, Masha Kocherginski, Jennifer Wu, Matthew Schipma, Brian Wray, John Griffiths, Richard Unwin, Simon Clark, Rajesh Acharya, Riyue Bao, Craig Horbinski, Rimas Lukas, Gary Schiltz, Derek Wainwright
Meeting Abstract
Oncology
Miri Kim, Erik Ladomersky, Lijie Zhai, Lakshmi Bollu, April Bell, Kristen Lauing, Erik Rabin, Craig Horbinski, Rimas Lukas, Derek Wainwright
Meeting Abstract
Oncology
Erik Ladomersky, Lijie Zhai, Lakshmi Bollu, April Bell, Kristen Lauing, Rimas Lukas, Derek Wainwright
Meeting Abstract
Oncology
Lakshmi Bollu, Prashant Bommi, Derek Wainwright, Erik Ladomersky, Lijie Zhai, April Bell, Kristen Lauing
Article
Oncology
Na Niu, Jun Yao, Robert C. Bast, Anil K. Sood, Jinsong Liu
Summary: The research revealed that IL-6 plays a crucial role in the formation and transformation of PGCCs into CAFs, and blocking IL-6 can attenuate tumor growth and inhibit drug resistance.
Article
Chemistry, Multidisciplinary
Joshua P. Gray, Md. Nasir Uddin, Rajan Chaudhari, Margie N. Sutton, Hailing Yang, Philip Rask, Hannah Locke, Brian J. Engel, Nefeli Batistatou, Jing Wang, Brian J. Grindel, Pratip Bhattacharya, Seth T. Gammon, Shuxing Zhang, David Piwnica-Worms, Joshua A. Kritzer, Zhen Lu, Robert C. Bast, Steven W. Millward
Summary: Autophagy induction has been found to play a crucial role in the development of treatment resistance and dormancy in various cancer types. Current autophagy inhibitors, such as chloroquine and hydroxychloroquine, face challenges of poor pharmacokinetics and high toxicity at therapeutic dosages. Through the use of Scanning Unnatural Protease Resistant (SUPR) mRNA display, macrocyclic peptides targeting the autophagy protein LC3 were developed, showing promising results in sensitizing platinum-resistant ovarian cancer cells to chemotherapy. These peptides disrupted protein-protein interactions and inhibited autophagic flux, leading to significant tumor growth inhibition in mouse models of metastatic ovarian cancer.