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Personal Mutanomes Meet Modern Oncology Drug Discovery and Precision Health

Feixiong Cheng, Han Liang, Atul J. Butte, Charis Eng, Ruth Nussinov, Michael M. Gottesman
2018 Pharmacological Reviews  
The three-dimensional protein structural view of personal mutanomes sheds light on the functional consequences of clinically actionable mutations revealed in tumor diagnosis and followed up in personalized  ...  In this review, we describe the protein structural landscape of personal mutanomes and provide expert opinions on rational strategies for more streamlined oncological drug discovery and molecularly targeted  ...  Wang and colleagues examined RNA-seq data from 37 patients with chronic lymphocytic leukemia and found that SF3B1 mutations increased the telomerase activity, Notch signaling, and DNA damage, by promoting  ... 
doi:10.1124/pr.118.016253 pmid:30545954 pmcid:PMC6294046 fatcat:njxfrnuje5fyzdtajf7aakuslu

Recurrent reciprocal RNA chimera involving YPEL5 and PPP1CB in chronic lymphocytic leukemia

T. Velusamy, N. Palanisamy, S. Kalyana-Sundaram, A. A. Sahasrabuddhe, C. A. Maher, D. R. Robinson, D. W. Bahler, T. T. Cornell, T. E. Wilson, M. S. Lim, A. M. Chinnaiyan, K. S. J. Elenitoba-Johnson
2013 Proceedings of the National Academy of Sciences of the United States of America  
Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults in the Western hemisphere.  ...  phosphatase PP1-beta catalytic subunit | B-lymphoid malignancy B -cell chronic lymphocytic leukemia (B-CLL) is the most common form of leukemia in adults in Western countries (1).  ...  The authors declare no conflict of interest. This article is a PNAS Direct Submission.  ... 
doi:10.1073/pnas.1214326110 pmid:23382248 pmcid:PMC3581970 fatcat:wqvolyvwdbc73kcacjxehaatw4

JAK inhibitors for the treatment of myeloproliferative neoplasms and other disorders

William Vainchenker, Emilie Leroy, Laure Gilles, Caroline Marty, Isabelle Plo, Stefan N. Constantinescu
2018 F1000Research  
Despite a weak effect on the cause of the disease itself in MPNs, it improves the clinical state of patients and increases survival in myelofibrosis.  ...  JAK inhibitors have been developed following the discovery of the V617F JAK2 in 2005 as the driver mutation of the majority of non-BCR-ABL1 myeloproliferative neoplasms (MPNs).  ...  This occurs in several types of lymphoma as well as in chronic lymphocytic leukemia and Waldenström macroglobulinemia 58 .  ... 
doi:10.12688/f1000research.13167.1 pmid:29399328 pmcid:PMC5773931 fatcat:2536ogr5lvemxlhnyfe2cgczqa

The Human Proteome Organization Chromosome 6 Consortium: Integrating chromosome-centric and biology/disease driven strategies

C.H. Borchers, J. Kast, L.J. Foster, K.W.M. Siu, C.M. Overall, T.A. Binkowski, W.H. Hildebrand, A. Scherer, M. Mansoor, P.A. Keown
2014 Journal of Proteomics  
Chromosome 6 (Ch6) provides an excellent model for integration of these two tasks. This metacentric chromosome has a complement of 1002-1034 genes that code for known, novel or putative proteins.  ...  Ch6 is functionally associated with more than 120 major human diseases, many with high population prevalence, devastating clinical impact and profound societal consequences.  ...  Deletions in 6q21 occur in 7% of B-cell chronic lymphocytic leukemias (B-CLL) [25] and of 6q27 in 21% of patients with CLL, while deletions in the long arm of chromosome 6 are related to diffuse B-cell  ... 
doi:10.1016/j.jprot.2013.08.001 pmid:23933161 pmcid:PMC4096956 fatcat:ph5iovegmrdgjfhkohvemoyr7i

A Systematic Review on the Contribution of Artificial Intelligence in the Development of Medicines for COVID-2019

Carla Pires
2021 Journal of Personalized Medicine  
Among other, the selected studies on new treatments against COVID-2019 were classified, as follows: studies with in-vitro and/or clinical data; association of known drugs; and other studies related to  ...  repurposing of drugs.  ...  Conflicts of Interest: The author declares no conflict of interest.  ... 
doi:10.3390/jpm11090926 pmid:34575703 fatcat:ldgzoqcddbgmziegmvaujucr2i

Recurrent Rearrangements in Prostate Cancer: Causes and Therapeutic Potential

Nicole M. White, Felix Y. Feng, Christopher A. Maher
2013 Current Drug Targets  
of prostate cancer patients.  ...  However, gene fusions as driver mutations in cancer have classically been a distinction in leukemia and other rare instances until recently with the discovery of gene fusion events occurring in 50 to 75%  ...  The classical example of gene rearrangements is the Philadelphia chromosome found in chronic myelogenous leukemia (CML) consisting of the translocation of chromosome 9 and 22 creating BCR-ABL, an activated  ... 
doi:10.2174/1389450111314040006 pmid:23410129 pmcid:PMC3733264 fatcat:yrb6yalwnjbk7ookvvfav3r3ee

Potential mechanisms of resistance to venetoclax and strategies to circumvent it

Stephen K. Tahir, Morey L. Smith, Paul Hessler, Lisa Roberts Rapp, Kenneth B. Idler, Chang H. Park, Joel D. Leverson, Lloyd T. Lam
2017 BMC Cancer  
Venetoclax (ABT-199), a first-in-class orally bioavailable BCL-2-selective inhibitor, was recently approved by the FDA for use in patients with 17p-deleted chronic lymphocytic leukemia who have received  ...  It is also being evaluated in numerous clinical trials for treating patients with various hematologic malignancies.  ...  Acknowledgements We thank past and present members of the BCL-2 project team for helpful discussions.  ... 
doi:10.1186/s12885-017-3383-5 pmid:28578655 pmcid:PMC5457565 fatcat:5ugecue4dvgsbedemptflxjuhe

CDK9: A Comprehensive Review of Its Biology, and Its Role as a Potential Target for Anti-Cancer Agents

Abel Tesfaye Anshabo, Robert Milne, Shudong Wang, Hugo Albrecht
2021 Frontiers in Oncology  
This therapeutic potential has been utilized for the discovery of CDK9 inhibitors, some of which have entered human clinical trials.  ...  in preclinical and clinical settings.  ...  Stereo ribbon plot of the 3D structure of CDK9-cyclin T1 in complex with ATP (Protein data bank: 3BLQ).  ... 
doi:10.3389/fonc.2021.678559 pmid:34041038 pmcid:PMC8143439 fatcat:ebsnc2h22baarhl63uvfefthou

Exploiting drug-disease relationships for computational drug repositioning

J. T. Dudley, T. Deshpande, A. J. Butte
2011 Briefings in Bioinformatics  
initiates from the clinical perspective of disease or its pathology.  ...  Finding new uses for existing drugs, or drug repositioning, has been used as a strategy for decades to get drugs to more patients.  ...  lymphocytic leukemia and rheumatoid arthritis).  ... 
doi:10.1093/bib/bbr013 pmid:21690101 pmcid:PMC3137933 fatcat:pcwnzy26ezg2rgymbyvgw3cjsq

In silico Molecular Docking Analysis of Imatinib to Target the Marker Proteins of Breast Cancer

V. Senthil Kumar, T. V. Ajay Kumar, V. Parthasarathy
2021 Current Journal of Applied Science and Technology  
The study helped to evaluate the pharmacokinetic properties and binding efficiency of Imatinib towards the breast cancer proteins.  ...  The results of study showed that the Imatinib exhibited better binding affinities to mTOR and HER2 as compared to ER, PARP and P53 proteins.  ...  Imatinib (Gleevec ® or Glivec ® ) is also known as a magical bullet developed by Nicholas Lyndon, a biochemist of Ciba-Geigy and the clinical trial was conducted with the patients of chronic myeloid leukemia  ... 
doi:10.9734/cjast/2021/v40i3631579 fatcat:tqgffrh3wndkzclmyylh22p6ya

Clinical epigenetics settings for cancer and cardiovascular diseases: real-life applications of network medicine at the bedside

Federica Sarno, the International Network Medicine Consortium, Giuditta Benincasa, Markus List, Albert-Lazlo Barabasi, Jan Baumbach, Fortunato Ciardiello, Sebastiano Filetti, Kimberly Glass, Joseph Loscalzo, Cinzia Marchese, Bradley A. Maron (+7 others)
2021 Clinical Epigenetics  
The study of epigenetic biomarkers has led to the identification of numerous drugs with an increasingly significant role in clinical therapy especially of cancer patients.  ...  Here, we provide an overview of clinical epigenetics within the context of network analysis.  ...  NM applications may improve our mechanistic understanding of tumorigenesis and the dynamics of driver and contributing (epi)mutations within the 3D structure of the cell and of tissues.  ... 
doi:10.1186/s13148-021-01047-z pmid:33785068 pmcid:PMC8010949 fatcat:vojcp6avfrdfzi2vero5iaznji

Breakpoint Analysis of Transcriptional and Genomic Profiles Uncovers Novel Gene Fusions Spanning Multiple Human Cancer Types

Craig P. Giacomini, Steven Sun, Sushama Varma, A. Hunter Shain, Marilyn M. Giacomini, Jay Balagtas, Robert T. Sweeney, Everett Lai, Catherine A. Del Vecchio, Andrew D. Forster, Nicole Clarke, Kelli D. Montgomery (+6 others)
2013 PLoS Genetics  
Gene fusions, like BCR/ABL1 in chronic myelogenous leukemia, have long been recognized in hematologic and mesenchymal malignancies.  ...  Taken together, we provide a robust approach for gene fusion discovery, and our results highlight a more widespread role of fusion genes in cancer pathogenesis.  ...  Acknowledgments The authors would like to thank the members of the Pollack lab for helpful discussion. Author Contributions  ... 
doi:10.1371/journal.pgen.1003464 pmid:23637631 pmcid:PMC3636093 fatcat:yi3eyariwfh5xgdsm7ts6mdby4

From Nanoparticles to Cancer Nanomedicine: Old Problems with New Solutions

Chi-Ling Chiang, Ming-Huei Cheng, Chih-Hsin Lin
2021 Nanomaterials  
for cancer patients.  ...  Anticancer nanomedicines have been studied over 30 years, but fewer than 10 formulations have been approved for clinical therapy today.  ...  Conflicts of Interest: The authors declare no conflict of interest.  ... 
doi:10.3390/nano11071727 doaj:4868138b586a4a2db013e70594640c53 fatcat:pzig2ckbd5b67dkx6gqnyf7iru

Tumor microenvironment and cancer therapy resistance

Yu Sun
2016 Cancer Letters  
In the long run, continued inputs into translational medicine remain highly desired to achieve durable responses in the current era of personalized clinical oncology.  ...  Innate resistance to various therapeutic interventions is a hallmark of cancer.  ...  Acknowledgements The author sincerely apologizes for not being able to thoroughly cite the contribution of all studies related to the current topic due to space restriction, and gratefully  ... 
doi:10.1016/j.canlet.2015.07.044 pmid:26272180 fatcat:5o3k4jo325adpfrt2udnhmsyvq

Use of Cell and Genome Modification Technologies to Generate Improved "Off-the-Shelf" CAR T and CAR NK Cells

Michael A. Morgan, Hildegard Büning, Martin Sauer, Axel Schambach
2020 Frontiers in Immunology  
The feasibility and safety of such approaches is currently tested in clinical trials.  ...  which are ever more commonly introduced into cancer patient treatment protocols.  ...  to Alemtuzumab (Campath R ), which is an antibody used to eliminate CD52 + lymphocytes in B-cell chronic lymphocytic leukemia (66) .  ... 
doi:10.3389/fimmu.2020.01965 pmid:32903482 pmcid:PMC7438733 fatcat:e4pwswh3krcqthzdnei6y3ymza
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