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Author Daruka Mahadevan

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Rare Tumor-Normal Matched Whole Exome Sequencing Identifies Novel Genomic Pathogenic Germline and Somatic Aberrations.

Ryan Sprissler, Bryce Perkins, Laurel Johnstone, Hani M Babiker, Pavani Chalasani, Branden Lau, Michael Hammer, Daruka Mahadevan,

Whole exome sequencing (WES) of matched tumor-normal pairs in rare tumors has the potential to identify genome-wide mutations and copy number alterations (CNAs). We evaluated 27 rare cancer patients with tumor-normal matching by WES and tumor-only next generation sequencing (NGS) as a comparator. Our goal was to: 1) identify known ... Read more >>

Cancers (Basel) (Cancers)
[2020, 12(6):]

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Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study.

Nicole M Kuderer, Toni K Choueiri, Dimpy P Shah, Yu Shyr, Samuel M Rubinstein, Donna R Rivera, Sanjay Shete, Chih-Yuan Hsu, Aakash Desai, Gilberto de Lima Lopes, Petros Grivas, Corrie A Painter, Solange Peters, Michael A Thompson, Ziad Bakouny, Gerald Batist, Tanios Bekaii-Saab, Mehmet A Bilen, Nathaniel Bouganim, Mateo Bover Larroya, Daniel Castellano, Salvatore A Del Prete, Deborah B Doroshow, Pamela C Egan, Arielle Elkrief, Dimitrios Farmakiotis, Daniel Flora, Matthew D Galsky, Michael J Glover, Elizabeth A Griffiths, Anthony P Gulati, Shilpa Gupta, Navid Hafez, Thorvardur R Halfdanarson, Jessica E Hawley, Emily Hsu, Anup Kasi, Ali R Khaki, Christopher A Lemmon, Colleen Lewis, Barbara Logan, Tyler Masters, Rana R McKay, Ruben A Mesa, Alicia K Morgans, Mary F Mulcahy, Orestis A Panagiotou, Prakash Peddi, Nathan A Pennell, Kerry Reynolds, Lane R Rosen, Rachel Rosovsky, Mary Salazar, Andrew Schmidt, Sumit A Shah, Justin A Shaya, John Steinharter, Keith E Stockerl-Goldstein, Suki Subbiah, Donald C Vinh, Firas H Wehbe, Lisa B Weissmann, Julie Tsu-Yu Wu, Elizabeth Wulff-Burchfield, Zhuoer Xie, Albert Yeh, Peter P Yu, Alice Y Zhou, Leyre Zubiri, Sanjay Mishra, Gary H Lyman, Brian I Rini, Jeremy L Warner, ,

BACKGROUND:Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness. METHODS:In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged ... Read more >>

Lancet (Lancet (London, England))
[2020, 395(10241):1907-1918]

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Janus Face of Drug-Induced Tetraploidy in Non-Hodgkin Lymphoma.

Daruka Mahadevan, Gregory C Rogers,

Anticancer agents often cause drug-induced tetraploidy (DIT) in cancer cells. DIT is not only a mechanism of inherited drug resistance, but proliferating DIT cells can produce progeny with increased ploidy or aneuploid genomes that drive aggressive disease. Here, we explore combinatorial therapeutic strategies for either preventing or eliminating DIT cells. ... Read more >>

Trends Cancer (Trends in cancer)
[2020, :]

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A Comparative Analysis of Tumors and Plasma Circulating Tumor DNA in 145 Advanced Cancer Patients Annotated by 3 Core Cellular Processes.

Kristian Larson, Radhamani Kannaiyan, Ritu Pandey, Yuliang Chen, Hani M Babiker, Daruka Mahadevan,

Matched-targeted and immune checkpoint therapies have improved survival in cancer patients, but tumor heterogeneity contributes to drug resistance. Our study categorized gene mutations from next generation sequencing (NGS) into three core processes. This annotation helps decipher complex biologic interactions to guide therapy. We collected NGS data on 145 patients who ... Read more >>

Cancers (Basel) (Cancers)
[2020, 12(3):]

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In Silico analyses of host immunity and stroma provide prognostic factors in early stage pancreatic ductal adenocarcinoma (PDAC).

Madison H Williams, Daruka Mahadevan,

Ann Transl Med (Annals of translational medicine)
[2020, 8(6):259]

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Adenosine 2A Receptor Blockade as an Immunotherapy for Treatment-Refractory Renal Cell Cancer.

Lawrence Fong, Andrew Hotson, John D Powderly, Mario Sznol, Rebecca S Heist, Toni K Choueiri, Saby George, Brett G M Hughes, Matthew D Hellmann, Dale R Shepard, Brian I Rini, Shivaani Kummar, Amy M Weise, Matthew J Riese, Ben Markman, Leisha A Emens, Daruka Mahadevan, Jason J Luke, Ginna Laport, Joshua D Brody, Leonel Hernandez-Aya, Philip Bonomi, Jonathan W Goldman, Lyudmyla Berim, Daniel J Renouf, Rachel A Goodwin, Brian Munneke, Po Y Ho, Jessica Hsieh, Ian McCaffery, Long Kwei, Stephen B Willingham, Richard A Miller,

Adenosine mediates immunosuppression within the tumor microenvironment through triggering adenosine 2A receptors (A2AR) on immune cells. To determine whether this pathway could be targeted as an immunotherapy, we performed a phase I clinical trial with a small-molecule A2AR antagonist. We find that this molecule can safely block adenosine signaling in ... Read more >>

Cancer Discov (Cancer discovery)
[2020, 10(1):40-53]

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Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) in Pancreatic Ductal Adenocarcinoma (PDA): An integrative analysis of a novel therapeutic target.

Ritu Pandey, Muhan Zhou, Shariful Islam, Baowei Chen, Natalie K Barker, Paul Langlais, Anup Srivastava, Moulun Luo, Laurence S Cooke, Eric Weterings, Daruka Mahadevan,

We investigated biomarker CEACAM6, a highly abundant cell surface adhesion receptor that modulates the extracellular matrix (ECM) in pancreatic ductal adenocarcinoma (PDA). The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) RNA-Seq data from PDA patients were analyzed for CEACAM6 expression and evaluated for overall survival, association, enrichment and ... Read more >>

Sci Rep (Scientific reports)
[2019, 9(1):18347]

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DNA methylation biomarkers discovered in silico detect cancer in liquid biopsies from non-small cell lung cancer patients.

Lukas Vrba, Marc M Oshiro, Samuel S Kim, Linda L Garland, Crystal Placencia, Daruka Mahadevan, Mark A Nelson, Bernard W Futscher,

Identification of cancer-specific methylation of DNA released by tumours can be used for non-invasive diagnostics and monitoring. We previously reported in silico identification of DNA methylation loci specifically hypermethylated in common human cancers that could be used as epigenetic biomarkers. Using DNA methylation specific qPCR we now clinically tested a ... Read more >>

Epigenetics (Epigenetics)
[2020, 15(4):419-430]

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PD-1-Associated Gene Expression Signature of Neoadjuvant Trastuzumab-Treated Tumors Correlates with Patient Survival in HER2-Positive Breast Cancer.

William P D Hendricks, Natalia Briones, Rebecca F Halperin, Salvatore Facista, Paul R Heaton, Daruka Mahadevan, Suwon Kim,

The therapeutic HER2-targeting antibody trastuzumab has been shown to elicit tumor immune response in a subset of HER2-positive (HER2+) breast cancer. We performed genomic and immunohistochemical profiling of tumors from eight patients who have completed multiple rounds of neoadjuvant trastuzumabb to identify predictive biomarkers for trastuzumab-elicited tumor immune responses. Immunohistochemistry ... Read more >>

Cancers (Basel) (Cancers)
[2019, 11(10):]

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Phase I study of samalizumab in chronic lymphocytic leukemia and multiple myeloma: blockade of the immune checkpoint CD200.

Daruka Mahadevan, Mark C Lanasa, Charles Farber, Manjari Pandey, Maria Whelden, Susan J Faas, Terrie Ulery, Anjli Kukreja, Lan Li, Camille L Bedrosian, Xiaoping Zhang, Leonard T Heffner,

PURPOSE:Samalizumab is a novel recombinant humanized monoclonal antibody that targets CD200, an immunoregulatory cell surface member of the immunoglobulin superfamily that dampens excessive immune responses and maintains self-tolerance. This first-in-human study investigated the therapeutic use of samalizumab as a CD200 immune checkpoint inhibitor in chronic lymphocytic leukemia (CLL) and multiple ... Read more >>

J Immunother Cancer (Journal for immunotherapy of cancer)
[2019, 7(1):227]

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Everolimus for the treatment of advanced pancreatic ductal adenocarcinoma (PDAC).

Hani M Babiker, Michael Karass, Alejandro Recio-Boiles, Sreenivasa R Chandana, Ali McBride, Daruka Mahadevan,

Introduction: PDAC is a lethal malignancy with a clear unmet need; almost all patients fail 1st, 2nd, and 3rd line multi-agent cytotoxic chemotherapy. The mammalian target of rapamycin (mTOR) has been identified as a key signaling node enhancing tumor survival and drug resistance in PDAC; hence, it is considered a ... Read more >>

Expert Opin Investig Drugs (Expert opinion on investigational drugs)
[2019, 28(7):583-592]

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PD-1 Inhibition Achieves a Complete Metabolic Response in a Patient with Malignant Peripheral Nerve Sheath Tumor.

Lisa E Davis, Lauren A Nicholls, Hani M Babiker, Joy Liau, Daruka Mahadevan,

High-grade malignant peripheral nerve sheath tumors (MPNST) have a poor prognosis with limited responsiveness to systemic therapy. We document a case of a complete metabolic response to pembrolizumab monotherapy in metastatic disease. Tumor molecular profiling identified programmed-death ligand-1 (PD-L1) positivity. This characteristic provided a rationale for immune-checkpoint therapy. Treatment with ... Read more >>

Cancer Immunol Res (Cancer immunology research)
[2019, 7(9):1396-1400]

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A Multidisciplinary Evaluation of Barriers to Enrolling Cancer Patients into Early Phase Clinical Trials: Challenges and Patient-centric Recommendations.

Hani M Babiker, Lisa Davis, Kristian Larson, Crystal Placencia, Connor Swensen, Pavan Tenneti, Melissa Lim, Ruth Cañamar, Jacqueline Curtis, Erica Castillo, James Mancuso, Diane Rensvold, Sarah Martinez, Lora Macias, Alejandro Recio-Boiles, Sreenivasa R Chandana, Daruka Mahadevan,

Introduction: Early phase clinical trials are the first clinical research step to bringing new cancer therapeutics to patients. At this stage, a new drug's safety, dosing, and scheduling profiles are established as the main endpoints. However, excellent responses due to biomarker-guided and immune checkpoint trials in early phase have resulted ... Read more >>

Expert Opin Investig Drugs (Expert opinion on investigational drugs)
[2019, 28(8):675-686]

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A call to arms: Unifying the fight against resistance.

Alexis Kaushansky, Lizbeth Hedstrom, Aaron Goldman, Juswinder Singh, Priscilla L Yang, Pradipsinh K Rathod, Michael Cynamon, Dominik Wodarz, Daruka Mahadevan, Andrew Tomaras, Manuel A Navia, Celia A Schiffer,

This Editorial discusses the state of research on drug resistance in the fields of cancer, infectious disease, and agriculture. Reaching across the aisle for a more cross-collaborative approach may lead to exciting breakthroughs toward tackling the challenges of drug resistance in each field. ... Read more >>

Sci Signal (Science signaling)
[2018, 11(553):]

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Drug-induced aneuploidy and polyploidy is a mechanism of disease relapse in MYC/BCL2-addicted diffuse large B-cell lymphoma.

Shariful Islam, Andrew L Paek, Michael Hammer, Savithri Rangarajan, Robert Ruijtenbeek, Laurence Cooke, Eric Weterings, Daruka Mahadevan,

Double-hit (DH) or double-expresser (DE) lymphomas are high-grade diffuse large B-cell lymphomas (DLBCL) that are mostly incurable with standard chemo-immunotherapy due to treatment resistance. The generation of drug-induced aneuploid/polyploid (DIAP) cells is a common effect of anti-DLBCL therapies (e.g. vincristine, doxorubicin). DIAP cells are thought to be responsible for treatment ... Read more >>

Oncotarget (Oncotarget)
[2018, 9(89):35875-35890]

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Therapeutic trends in pancreatic ductal adenocarcinoma (PDAC).

Sreenivasa Chandana, Hani M Babiker, Daruka Mahadevan,

INTRODUCTION:Prognosis remains dismal for pancreatic ductal adenocarcinoma (PDAC). Genomics and proteomics have depicted heterogeneity in PDAC. Collectively, this information could be useful in improving diagnosis, prognosis, modalities of therapy, treatment responses, deciphering drug resistance and new drug development. AREAS COVERED:We describe major advances in the cellular and molecular subtypes based ... Read more >>

Expert Opin Investig Drugs (Expert opinion on investigational drugs)
[2019, 28(2):161-177]

Cited: 4 times

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RTHP-09. DYSREGULATION OF Wnt SIGNALING PATHWAY CORRELATES WITH TREATMENT OUTCOME IN GLIOBLASTOMA MULTIFORME.

Eric Weterings, Christopher Morrison, Nicholas Gravbrot, Michael Hammer, Daruka Mahadevan, Baldassarre Stea,

AbstractGlioblastoma multiforme (GBM) is the most common and most aggressive primary brain cancer with a median life expectancy of 13–15 months after surgery and chemo-radiation treatment. GBM is hallmarked by a poor response to radiation therapy (RT), which is generally attributed to upregulation of several DNA repair pathways. To identify ... Read more >>

Neuro-oncology (Neuro-oncology)
[2018, 20(Suppl 6):vi227-vi227]

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A comprehensive review of protein kinase inhibitors for cancer therapy.

Radhamani Kannaiyan, Daruka Mahadevan,

INTRODUCTION:Protein kinases are involved in various cellular functions. About 2% of the human genome encodes for protein kinases. Dysregulation of protein kinases is implicated in various processes of carcinogenesis. The advent of protein kinase inhibitors in cancer therapy has led to a paradigm shift in cancer therapy. Several protein kinase ... Read more >>

Expert Rev Anticancer Ther (Expert review of anticancer therapy)
[2018, 18(12):1249-1270]

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Phase I Study of the Investigational Aurora A Kinase Inhibitor Alisertib plus Rituximab or Rituximab/Vincristine in Relapsed/Refractory Aggressive B-cell Lymphoma.

Kevin R Kelly, Jonathan W Friedberg, Steven I Park, Kevin McDonagh, John Hayslip, Daniel Persky, Jia Ruan, Soham Puvvada, Peter Rosen, Swaminathan Padmanabhan Iyer, Alexandra Stefanovic, Steven H Bernstein, Steven Weitman, Anand Karnad, Gregory Monohan, Ari VanderWalde, Raul Mena, Monika Schmelz, Catherine Spier, Susan Groshen, Karthik Venkatakrishnan, Xiaofei Zhou, Emily Sheldon-Waniga, E Jane Leonard, Daruka Mahadevan,

PURPOSE:The aurora A kinase inhibitor alisertib demonstrated single-agent clinical activity and preclinical synergy with vincristine/rituximab in B-cell non-Hodgkin lymphoma (B-NHL). This phase I study aimed to determine the safety and recommended phase II dose (RP2D) of alisertib in combination with rituximab ± vincristine in patients with relapsed/refractory aggressive B-NHL. PATIENTS ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2018, 24(24):6150-6159]

Cited: 2 times

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Abemaciclib in Combination with Single-Agent Options in Patients with Stage IV Non-Small Cell Lung Cancer: A Phase Ib Study.

Edward S Kim, Karen Kelly, Luis G Paz-Ares, Pilar Garrido, Shadia Jalal, Daruka Mahadevan, Martin Gutierrez, Mariano Provencio, Eric Schaefer, Monte Shaheen, Erica L Johnston, P Kellie Turner, Siva Rama Prasad Kambhampati, Richard Beckmann, Anwar Hossain, William J John, Jonathan W Goldman,

Purpose: Abemaciclib, a dual inhibitor of cyclin-dependent kinases 4 and 6, has demonstrated preclinical activity in non-small cell lung cancer (NSCLC). A multicenter, nonrandomized, open-label phase Ib study was conducted to test safety, MTD, pharmacokinetics, and preliminary antitumor activity of abemaciclib in combination with other therapies for treatment in patients ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2018, 24(22):5543-5551]

Cited: 1 time

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A phase 1, first-in-human study of AMG 900, an orally administered pan-Aurora kinase inhibitor, in adult patients with advanced solid tumors.

Michael Carducci, Montaser Shaheen, Ben Markman, Sara Hurvitz, Daruka Mahadevan, Dusan Kotasek, Oscar B Goodman, Erik Rasmussen, Vincent Chow, Gloria Juan, Gregory R Friberg, Erick Gamelin, Florian D Vogl, Jayesh Desai,

Background Aurora kinase overexpression or amplifications are associated with high proliferation, poor prognosis, and therapeutic resistance in human tumors. AMG 900 is an investigational, oral, selective pan-Aurora kinase inhibitor. Methods This first-in-human trial included dose-escalation and dose-expansion phases ( ClinicalTrials.gov : NCT00858377). Dose escalation evaluated the safety, tolerability, and pharmacokinetics ... Read more >>

Invest New Drugs (Investigational new drugs)
[2018, 36(6):1060-1071]

Cited: 2 times

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Yttrium-90-Ibritumomab Tiuxetan (Zevalin®) Radioimmunotherapy after Cytoreduction with ESHAP Chemotherapy in Patients with Relapsed Follicular Non-Hodgkin Lymphoma: Final Results of a Phase II Study.

Soham D Puvvada, José M Guillén-Rodríguez, Jessica Yan, Lora Inclán, Kara Heard, Xavier I Rivera, Faiz Anwer, Daruka Mahadevan, Jonathan H Schatz, Daniel O Persky,

BACKGROUND:Radioimmunotherapy (RIT) is effective in treating relapsed/refractory follicular lymphoma (FL), with durable remissions in first-line consolidation. We hypothesized that RIT with ibritumomab tiuxetan (Zevalin®) would result in durable remissions by eliminating minimal residual disease after cytoreduction. METHODS:Patients with FL received 2 cycles of ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) every 28 ... Read more >>

Oncology (Oncology)
[2018, 94(5):274-280]

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Ublituximab for the treatment of CD20 positive B-cell malignancies.

Hani M Babiker, Ashley E Glode, Laurence S Cooke, Daruka Mahadevan,

INTRODUCTION:Non-Hodgkin lymphoma (NHL) is the most common adult hematologic malignancy. Conventional methods of treatment are chemotherapy and radiation, which were associated with toxicities and lack of specificity. Potential cell surface targets for treatment of B-cell NHL (B-NHL) include CD19, CD20, and CD22 which are highly expressed on malignant B-cells. The ... Read more >>

Expert Opin Investig Drugs (Expert opinion on investigational drugs)
[2018, 27(4):407-412]

Cited: 2 times

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Co-targeting aurora kinase with PD-L1 and PI3K abrogates immune checkpoint mediated proliferation in peripheral T-cell lymphoma: a novel therapeutic strategy.

Shariful Islam, Eric Vick, Bryan Huber, Carla Morales, Catherine Spier, Laurence Cooke, Eric Weterings, Daruka Mahadevan,

Peripheral T-cell non-Hodgkin lymphoma (PTCL) are heterogeneous, rare, and aggressive diseases mostly incurable with current cell cycle therapies. Aurora kinases (AKs) are key regulators of mitosis that drive PTCL proliferation. Alisertib (AK inhibitor) has a response rate ∼30% in relapsed and refractory PTCL (SWOG1108). Since PTCL are derived from CD4+/CD8+ ... Read more >>

Oncotarget (Oncotarget)
[2017, 8(59):100326-100338]

Cited: 4 times

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Correction to: Phase II study of bi-weekly temozolomide plus bevacizumab for adult patients with recurrent glioblastoma.

Michael A Badruddoja, Marjorie Pazzi, Abhay Sanan, Kurt Schroeder, Kevin Kuzma, Thomas Norton, Thomas Scully, Daruka Mahadevan, Michael Malek Ahmadi,

Cancer Chemother. Pharmacol. (Cancer chemotherapy and pharmacology)
[2018, 81(1):223]

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