Integration of pan-omics technologies and three-dimensional in vitro tumor models: an approach toward drug discovery and precision medicine – Molecular Cancer
Despite advancements in treatment protocols, cancer is one of the leading cause of deaths worldwide. Therefore, there is a need to identify newer and personalized therapeutic targets along with screening technologies to combat cancer. With the advent of pan-omics technologies, such as genomics, transcriptomics, proteomics, metabolomics, and lipidomics, the scientific community has witnessed an improved molecular and metabolomic understanding of various diseases, including cancer. In addition, three-dimensional (3-D) disease models have been efficiently utilized for understanding disease pathophysiology and as screening tools in drug discovery. An integrated approach utilizing pan-omics technologies and 3-D in vitro tumor models has led to improved understanding of the intricate network encompassing various signalling pathways and molecular cross-talk in solid tumors. In the present review, we underscore the current trends in omics technologies and highlight their role in understanding genotypic-phenotypic co-relation in cancer with respect to 3-D in vitro tumor models. We further discuss the challenges associated with omics technologies and provide our outlook on the future applications of these technologies in drug discovery and precision medicine for improved management of cancer. Graphical Abstract
Integration of pan-omics technologies and three-dimensional in vitro tumor models: an approach toward drug discovery and precision medicine
by Anmi Jose, Pallavi Kulkarni, Jaya Thilakan, Murali Munisamy, Anvita Gupta Malhotra, Jitendra Singh, Ashok Kumar, Vivek M Rangnekar, Neha Arya, Mahadev Rao
Mol Cancer 2024 Mar 9;23(1):50
Impact Factor: 37.4
Predictive performance of population pharmacokinetic models of imatinib in chronic myeloid leukemia patients – Cancer Chemotherapy and Pharmacology
Background and aim Chronic myeloid leukemia is a myeloproliferative neoplasm associated with the specific chromosomal translocation known as the Philadelphia chromosome. Imatinib is a potent BCR-ABL tyrosine kinase inhibitor, which is approved as the first line therapy for CML patients. There are various population pharmacokinetic studies available in the literature for this population. However, their use in other populations outside of their cohort for the model development has not been evaluated. This study was aimed to perform the predictive performance of the published population pharmacokinetic models for imatinib in CML population and propose a dosing nomogram. Methods A systematic review was conducted through PubMed, and WoS databases to identify PopPK models. Clinical data collected in adult CML patients treated with imatinib was used for evaluation of these models. Various prediction-based metrics were used for assessing the bias and precision of PopPK models using individual predictions. Results Eight imatinib PopPK model were selected for evaluating the model performance. A total of 145 plasma imatinib samples were collected from 43 adult patients diagnosed with CML and treated with imatinib. The PopPK model reported by Menon et al. had better performance than all other PopPK models. Conclusion Menon et al. model was able to predict well for our clinical data where it had the relative mean prediction error percentage ≤ 20%, relative median absolute prediction error ≤ 30% and relative root mean square error close to zero. Based on this final model, we proposed a dosing nomogram for various weight groups, which could potentially help to maintain the trough concentrations in the therapeutic range.
Predictive performance of population pharmacokinetic models of imatinib in chronic myeloid leukemia patients.
by Jaya Shree Dilli Batcha, Vikram Gota, Saikumar Matcha, Arun Prasath Raju, Mahadev Rao, Karthik S. Udupa, Surulivelrajan Mallayasamy
Cancer Chemother Pharmacol 2024 Mar 5
Increased Gene Expression of C1orf74 Is Associated with Poor Prognosis in Cervical Cancer
C1orf74, also known as URCL4, has been reported to have higher expression and be associated with poor prognosis in lung adenocarcinoma patients, and its role in regulation of the EGFR/AKT/mTORC1 pathway has been recently elucidated. In the current study, we used publicly available data and experimen…
Increased Gene Expression of C1orf74 Is Associated with Poor Prognosis in Cervical Cancer
by Preetiparna Parida, Shirley Lewis, Krishna Sharan, Mehta Vedant Kamal, Naveena A. N. Kumar, Vishwapriya M. Godkhindi, Sooryanarayana Varambally, Vivek M. Rangnekar, Mahadev Rao, and Rama Rao Damerla
Cells 2023, 12(21), 2530.
Impact Factor: 6.0
Crizotinib induces Par-4 secretion from normal cells and GRP78 expression on the cancer cell surface for selective tumor growth inhibition
Lung cancer is the leading cause of cancer-related deaths. Lung cancer cells develop resistance to apoptosis by suppressing the secretion of the tumor suppressor Par-4 protein (also known as PAWR) and/or down-modulating the Par-4 receptor GRP78 on the…
Crizotinib induces Par-4 secretion from normal cells and GRP78 expression on the cancer cell surface for selective tumor growth inhibition(PDF)
by Ravshan Burikhanov, Saptadwipa Ganguly, Sally Ellingson, Vitaliy M Sviripa, Nathalia Araujo, Shunqiang Li, Prasanna Venkatraman, Mahadev Rao, Anuradha Choughule, Christine F Brainson, Chang-Guo Zhan, H Peter Spielmann, David S Watt, Ramaswamy Govindan, Vivek M Rangnekar
American Journal of Cancer Research 2023;13(3):976-991.
Impact Factor: 5.942
Factors Influencing Pharmacokinetics of Tamoxifen in Breast Cancer Patients: A Systematic Review of Population Pharmacokinetic Models
Background: Tamoxifen is useful in managing breast cancer and it is reported to have significant variability in its pharmacokinetics. This review aimed to summarize reported population pharmacokinetics studies of tamoxifen and to identify the factors affecting the pharmacokinetics of tamoxifen in ad…
Factors Influencing Pharmacokinetics of Tamoxifen in Breast Cancer Patients: A Systematic Review of Population Pharmacokinetic Models
by Jaya Shree Dilli Batcha, Arun Prasath Raju, Saikumar Matcha, Elstin Anbu Raj S., Karthik S. Udupa, Vikram Gota and Surulivelrajan Mallayasamy
Biology 2023, 12(1), 51
Impact Factor: 5.168
Local data commons: the sleeping beauty in the community of data commons – BMC Bioinformatics
Background Public Data Commons (PDC) have been highlighted in the scientific literature for their capacity to collect and harmonize big data. On the other hand, local data commons (LDC), located within an institution or organization, have been underrepresented in the scientific literature, even thou…
Local data commons: the sleeping beauty in the community of data commons.
by Jong Cheol Jeong, Isaac Hands, Jill M. Kolesar, Mahadev Rao, Bront Davis, York Dobyns, Joseph Hurt-Mueller, Justin Levens, Jenny Gregory, John Williams, Lisa Witt, Eun Mi Kim, Carlee Burton, Amir A. Elbiheary, Mingguang Chang & Eric B. Durbin
BMC Bioinformatics volume 23, Article number: 386 (2022)
Impact Factor: 3.169
Raman micro-spectroscopic map estimating in vivo precision of tumor ablative effect achieved by photothermal therapy procedure – PubMed
Photothermal-therapy (PTT) inculcates near-infrared laser guided local heating effect, where high degree of precision is expected, but not well proven to-date. An ex vivo tissue biochemical map with molecular/biochemical response showing the coverage area out of an optimized PTT procedure can reveal…
Raman micro-spectroscopic map estimating in vivo precision of tumor ablative effect achieved by photothermal therapy procedure.
by Sumit K.Mishra, Arti Hole, B. Pradeep K.Reddy, Rohit Srivastava, Murali Krishna Chilakapati, Abhijit De
Nanomedicine 2021 Oct;37:102437.
Impact Factor: 6.5
Integration of liquid biopsy and pharmacogenomics for precision therapy of EGFR mutant and resistant lung cancers – PubMed
The advent of molecular profiling has revolutionized the treatment of lung cancer by comprehensively delineating the genomic landscape of the epidermal growth factor receptor (EGFR) gene. Drug resistance caused by EGFR mutations and genetic polymorphisms of drug metabolizing enzymes and transporters…
Integration of liquid biopsy and pharmacogenomics for precision therapy of EGFR mutant and resistant lung cancers.
by Kolesar J, Peh S, Thomas L, Baburaj G, Mukherjee N, Kantamneni R, Lewis S, Pai A, Udupa KS, Kumar An N, Rangnekar VM, Rao M.
Mol Cancer. 2022 Feb 24;21(1):61.
Impact Factor: 41.14
Therapeutic opportunities in cancer therapy: targeting the p53-MDM2/MDMX interactions – PubMed
Ubiquitination is a key enzymatic post-translational modification that influences p53 stability and function. p53 protein regulates the expression of MDM2 (mouse double-minute 2 protein) E3 ligase and MDMX (double-minute 4 protein), through proteasome-based degradation. Exploration of targeting the…
Therapeutic opportunities in cancer therapy: targeting the p53-MDM2/MDMX interactions.
by Munisamy M, Mukherjee N, Thomas L, Pham AT, Shakeri A, Zhao Y, Kolesar J, Rao PPN, Rangnekar VM, Rao M.
Am J Cancer Res. 2021 Dec 15;11(12).
Impact Factor: 6.166
Value added by an inter-continental cancer consortium – PubMed
Value added by an inter-continental cancer consortium
Value added by an inter-continental cancer consortium.
by Rao M, Venkatraman P, Mukhopadhyay D, Roychoudhury S, Vanderford NL, Rangnekar VM.
Genes Cancer. 2021 May 21;12:65-68.
Impact Factor: 5.666
DACH1 mutation frequency in endometrial cancer is associated with high tumor mutation burden – PubMed
DACH1 mutations are prevalent in Kentucky patients with endometrial cancer. These mutations are associated with high tumor mutational burden and co-occur with genome destabilizing gene mutations. These findings suggest DACH1 may be a candidate biomarker for future trials with immunotherapy, particul…
DACH1 mutation frequency in endometrial cancer is associated with high tumor mutation burden.
by Riggs MJ, Lin N, Wang C, Piecoro DW, Miller RW, Hampton OA, Rao M, Ueland FR, Kolesar JM.
PLoS One. 2020 Dec 30;15(12).
Impact Factor: 3.240
Liquid biopsy approaches for pleural effusion in lung cancer patients – PubMed
Genomic profiling of tumors has become the mainstay for diagnosis, treatment monitoring and a guide to precision medicine. However, in clinical practice, the detection of driver mutations in tumors has several procedural limitations owing to progressive disease and tumor heterogeneity. The current e…
Liquid biopsy approaches for pleural effusion in lung cancer patients.
by Baburaj G, Damerla RR, Udupa KS, Parida P, Munisamy M, Kolesar J, Rao M.
Mol Biol Rep. 2020 Oct;47(10)
Impact Factor: 2.316
Histone Demethylase KDM5B as a Therapeutic Target for Cancer Therapy – PubMed
Lysine-specific demethylase 5B (KDM5B/PLU1/JARID1B) is found to be overexpressed in numerous malignancies, including breast, lung, skin, liver, and prostate cancer. Identification of molecules targeting the KDM5B enzyme could be a potential lead in cancer research. Although many KDM5B inhibitors wit…
Histone Demethylase KDM5B as a Therapeutic Target for Cancer Therapy.
by Jose A, Shenoy GG, Sunil Rodrigues G, Kumar NAN, Munisamy M, Thomas L, Kolesar J, Rai G, Rao PPN, Rao M.
Cancers (Basel). 2020 Jul 31;12(8):2121.
Impact Factor: 6.639
Potential Utility of Liquid Biopsy as a Diagnostic and Prognostic Tool for the Assessment of Solid Tumors: Implications in the Precision Oncology – PubMed
Liquid biopsy is a technique that utilizes circulating biomarkers in the body fluids of cancer patients to provide information regarding the genetic landscape of the cancer. It is emerging as an alternative and complementary diagnostic and prognostic tool to surgical biopsy in oncology. Liquid biops…
Potential Utility of Liquid Biopsy as a Diagnostic and Prognostic Tool for the Assessment of Solid Tumors: Implications in the Precision Oncology.
by Mathai RA, Vidya RVS, Reddy BS, Thomas L, Udupa K, Kolesar J, Rao M.
J Clin Med. 2019 Mar 18;8(3):373.
Impact Factor: 4.242
