Bhaskara, Srividya , PhD

Research Interests

  • Chromatin
  • Histone Deacetylases
  • Immunology
  • DNA Repair
  • DNA Replication
  • Cancer Biology
  • Cancer Therapeutics
  • Mouse Models of Cancer

Labs

Lab Website

Languages

  • English

Academic Information

  • Departments: Oncological Sciences - Adjunct Assistant Professor, Radiation Oncology - Associate Professor
  • Cancer Center Programs: Nuclear Control of Cell Growth & Differentiation

Academic Office Information

  • 801-213-4219
  • Huntsman Cancer Institute
    2000 Circle of Hope, Room: 4244
    Salt Lake City, UT 84112

Academic Bio

Dr. Bhaskara's research goal is to understand the functions for histone deacetylases (HDACs) in genome maintenance, with the ultimate objective of using the knowledge to improve the therapeutic benefits of HDAC inhibition as a treatment for cancer. In Dr. Bhaskara's post-doctoral research, she made the discovery that HDAC inhibitors induce cancer cell death by directly targeting genome stability programs independent of their effect on transcription. She showed HDAC inhibitors trigger genotoxic stress and death only in cycling cells, thereby providing a mechanistic explanation for how HDAC inhibitors selectively kill rapidly cycling cancer cells and not the quiescent normal cells. Using genetic deletion systems, she further found novel functions for HDAC3 in DNA repair, DNA replication, chromatin structure maintenance and B-cell development. Collectively, these findings provide a new paradigm for the mode-of-action of HDAC inhibitors, which are FDA-approved drugs for certain hematologic malignancies. As an independent investigator, Dr. Bhaskara's lab goal is to investigate the fundamental functions of HDACs in genome maintenance, with the ultimate objective of using the knowledge gained to test the therapeutic benefits of HDAC inhibition as a treatment for cancers including B-cell malignancies with an altered epigenetic state or aberrant genome maintenance program. Bhaskara's long-term goal is to effectively solve complex problems in cancer biology and rapidly move the field of cancer therapeutics forward to make a real difference in the lives of cancer patients. Dr. Bhaskara did her PhD in Dr. Ranjan Ganguly's lab at the University of Tennessee, Knoxville and performed her post-doctoral training at Vanderbilt University, Nashville in Dr. Scott Hiebert's lab.

Education History

Type School Degree
Research Fellow Vanderbilt University Medical Center
Biochemistry
Postdoctoral Research Fellow
Doctoral Training Department of Biochemistry, Cellular and Molecular Biology, University of Tennessee
Biochemistry
Ph.D.
Graduate Training Department of Biochemistry, Dr. A. L. M. Mudaliar Post-graduate Institute of Basic Medical Sciences,
Medical Biochemistry
M.S.
Undergraduate Department of Biochemistry, Mohammad Sathak College of Arts and Science, University of Madras
Biochemistry
B.S.

Global Impact

Education History

Type School Degree Country
Graduate Training Department of Biochemistry, Dr. A. L. M. Mudaliar Post-graduate Institute of Basic Medical Sciences,
Medical Biochemistry
M.S. India
Undergraduate Department of Biochemistry, Mohammad Sathak College of Arts and Science, University of Madras
Biochemistry
B.S. India

Selected Publications

Journal Article

  1. Stengel KR, Barnett KR, Wang J, Liu Q, Hodges E, Hiebert SW, Bhaskara S (2017 Aug 08). Deacetylase activity of histone deacetylase 3 is required for productive VDJ recombination and B-cell development. Proc Natl Acad Sci U S A, 114(32), 8608-8613.
  2. Tharkar-Promod S, Johnson DP, Bennett SE, Dennis EM, Banowsky BG, Jones SS, Shearstone JR, Quayle SN, Min C, Jarpe M, Mosbruger T, Pomicter AD, Miles RR, Chen WY, Bhalla KN, Zweidler-McKay PA, Shrieve DC, Deininger MW, Chandrasekharan MB, Bhaskara S (2017 Jun 05). HDAC1,2 inhibition and doxorubicin impair Mre11-dependent DNA repair and DISC to override BCR-ABL1-driven DSB repair in Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia.LID - 10.1038/leu.2017.174 [doi]. (Epub ahead of print) Leukemia.
  3. Chan E, Arlinghaus LR, Cardin DB, Goff L, Berlin JD, Parikh A, Abramson RG, Yankeelov TE, Hiebert S, Merchant N, Bhaskara S, Chakravarthy AB (2016 May). Phase I trial of vorinostat added to chemoradiation with capecitabine in pancreatic cancer. Radiother Oncol, 119(2), 312-8.
  4. Bhaskara S (2016 Jan 14). Examination of Proteins Bound to Nascent DNA in Mammalian Cells Using BrdU-ChIP-Slot-Western Technique. J Vis Exp, (107), e53647.
  5. Ramakrishnan S, Pokhrel S, Palani S, Pflueger C, Parnell TJ, Cairns BR, Bhaskara S, Chandrasekharan MB (2016 Jun 21). Counteracting H3K4 methylation modulators Set1 and Jhd2 co-regulate chromatin dynamics and gene transcription. Nat Commun, 7, 11949.
  6. Huang F, Ramakrishnan S, Pokhrel S, Pflueger C, Parnell TJ, Kasten MM, Currie SL, Bhachech N, Horikoshi M, Graves BJ, Cairns BR, Bhaskara S, Chandrasekharan MB (2015 Nov 27). Interaction of the Jhd2 Histone H3 Lys-4 Demethylase with Chromatin Is Controlled by Histone H2A Surfaces and Restricted by H2B Ubiquitination. J Biol Chem, 290(48), 28760-77.
  7. Abegglen LM, Caulin AF, Chan A, Lee K, Robinson R, Campbell MS, Kiso WK, Schmitt DL, Waddell PJ, Bhaskara S, Jensen ST, Maley CC, Schiffman JD (2015 Nov 03). Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans. JAMA, 314(17), 1850-60.
  8. Bhaskara S (2015). Histone deacetylases 1 and 2 regulate DNA replication and DNA repair: potential targets for genome stability-mechanism-based therapeutics for a subset of cancers. Cell Cycle, 14(12), 1779-85.
  9. Johnson DP, Spitz GS, Tharkar S, Quayle SN, Shearstone JR, Jones S, McDowell ME, Wellman H, Tyler JK, Cairns BR, Chandrasekharan MB, Bhaskara S (2015 Mar 10). HDAC1,2 inhibition impairs EZH2- and BBAP-mediated DNA repair to overcome chemoresistance in EZH2 gain-of-function mutant diffuse large B-cell lymphoma. Oncotarget, 6(7), 4863-87.
  10. Ha K, Fiskus W, Choi DS, Bhaskara S, Cerchietti L, Devaraj SG, Shah B, Sharma S, Chang JC, Melnick AM, Hiebert S, Bhalla KN (2014 Jul 30). Histone deacetylase inhibitor treatment induces 'BRCAness' and synergistic lethality with PARP inhibitor and cisplatin against human triple negative breast cancer cells. Oncotarget, 5(14), 5637-50.
  11. Hatzi K, Jiang Y, Garrett-Bakeman F, Gearhart MD, Giannopoulou EG, Zumbo P, Kirouac K, Bhaskara S, Polo JM, Kormaksson M, Mason CE, Hiebert SW, Prive GG, Bardwell VJ, Elemento O and Melnick A (). BCL6 selectively recruits functionally distinct corepressors to repress promoter and enhancer chromatin. Cell Rep, 4, 578-88.
  12. Wells CE, Bhaskara S, Stengel KR, Zhao Y, Sirbu B, Chagot B, Cortez D, Khabele D, Chazin WJ, Cooper A, Jacques V, Rusche J, Eischen CM, McGirt LY, Hiebert SW (2013). Inhibition of histone deacetylase 3 causes replication stress in cutaneous T cell lymphoma. PLoS ONE, 8(7), e68915.
  13. Hatzi K, Jiang Y, Huang C, Garrett-Bakelman F, Gearhart MD, Giannopoulou EG, Zumbo P, Kirouac K, Bhaskara S, Polo JM, Kormaksson M, MacKerell AD Jr, Xue F, Mason CE, Hiebert SW, Prive GG, Cerchietti L, Bardwell VJ, Elemento O, Melnick A (2013 Aug 15). A hybrid mechanism of action for BCL6 in B cells defined by formation of functionally distinct complexes at enhancers and promoters. Cell Rep, 4(3), 578-88.
  14. Summers AR, Fischer MA, Stengel KR, Zhao Y, Kaiser JF, Wells CE, Hunt A, Bhaskara S, Luzwick JW, Sampathi S, Chen X, Thompson MA, Cortez D, Hiebert SW (2013 Jul). HDAC3 is essential for DNA replication in hematopoietic progenitor cells. J Clin Invest, 123(7), 3112-23.
  15. Bhaskara S, Jacques V, Rusche JR, Olson EN, Cairns BR, Chandrasekharan MB (2013 Aug 15). Histone deacetylases 1 and 2 maintain S-phase chromatin and DNA replication fork progression. Epigenetics Chromatin, 6(1), 27.
  16. Ziesche E, Kettner-Buhrow D, Weber A, Wittwer T, Jurida L, Soelch J, Muller H, Newel D, Kronich P, Schneider H, Dittrich-Breiholz O, Bhaskara S, Hiebert SW, Hottiger MO, Li H, Burstein E, Schmitz ML, Kracht M (2013 Jan 07). The coactivator role of histone deacetylase 3 in IL-1-signaling involves deacetylation of p65 NF-kappaB. Nucleic Acids Res, 41(1), 90-109.
  17. Sirbu BM, Couch FB, Feigerle JT, Bhaskara S, Hiebert SW, Cortez D (2011 Jun 15). Analysis of protein dynamics at active, stalled, and collapsed replication forks. Genes Dev, 25(12), 1320-7.
  18. Wilson AJ, Holson E, Wagner F, Zhang YL, Fass DM, Haggarty SJ, Bhaskara S, Hiebert SW, Schreiber SL, Khabele D (2011 Sep 15). The DNA damage mark pH2AX differentiates the cytotoxic effects of small molecule HDAC inhibitors in ovarian cancer cells. Cancer Biol Ther, 12(6), 484-93.
  19. Bhaskara S, Hiebert SW (2011 Mar 01). Role for histone deacetylase 3 in maintenance of genome stability. Cell Cycle, 10(5), 727-8.
  20. Huang F, Chandrasekharan MB, Chen YC, Bhaskara S, Hiebert SW, Sun ZW (2010 Aug 06). The JmjN domain of Jhd2 is important for its protein stability, and the plant homeodomain (PHD) finger mediates its chromatin association independent of H3K4 methylation. J Biol Chem, 285(32), 24548-61.
  21. Bhaskara S, Knutson SK, Jiang G, Chandrasekharan MB, Wilson AJ, Zheng S, Yenamandra A, Locke K, Yuan JL, Bonine-Summers AR, Wells CE, Kaiser JF, Washington MK, Zhao Z, Wagner FF, Sun ZW, Xia F, Holson EB, Khabele D, Hiebert SW (2010 Nov 16). Hdac3 is essential for the maintenance of chromatin structure and genome stability. Cancer Cell, 18(5), 436-47.
  22. Knutson SK, Chyla BJ, Amann JM, Bhaskara S, Huppert SS, Hiebert SW (2008 Apr 09). Liver-specific deletion of histone deacetylase 3 disrupts metabolic transcriptional networks. EMBO J, 27(7), 1017-28.
  23. Bhaskara S, Chyla BJ, Amann JM, Knutson SK, Cortez D, Sun ZW, Hiebert SW (2008 Apr 11). Deletion of histone deacetylase 3 reveals critical roles in S phase progression and DNA damage control. Mol Cell, 30(1), 61-72.
  24. Chyla BJ, Moreno-Miralles I, Steapleton MA, Thompson MA, Bhaskara S, Engel M, Hiebert SW (2008 Oct). Deletion of Mtg16, a target of t(16;21), alters hematopoietic progenitor cell proliferation and lineage allocation. Mol Cell Biol, 28(20), 6234-47.
  25. Bhaskara S, Chandrasekharan MB, Ganguly R (2008 May 31). Caffeine induction of Cyp6a2 and Cyp6a8 genes of Drosophila melanogaster is modulated by cAMP and D-JUN protein levels. Gene, 415(1-2), 49-59.
  26. Bhaskara S, Dean ED, Lam V, Ganguly R (2006 Aug 01). Induction of two cytochrome P450 genes, Cyp6a2 and Cyp6a8, of Drosophila melanogaster by caffeine in adult flies and in cell culture. Gene, 377, 56-64.

Book

  1. Bhaskara S (). ALL, Philadelphia Chromosome, and HDAC1,2 Inhibitor. New York City: Springer.

Video/Film/CD/Web/Podcast

  1. Simonsen, H (). New Cancer Drug May be a Game Changer for Some Leukemia Patients [Video]. Salt Lake City: KSL.com. Available: http://www.ksl.com/?sid=44971645&nid=148.
  2. PTI (). Indian-Origin Scientist Develops New Drug to Treat Blood Cancer [Web]. New York: First Post. Available: http://www.firstpost.com/living/indian-origin-scientist-develops-new-drug-to-treat-blood-cancer-developed-3539227.html.
  3. Protyush (). This New Drug May Benefit Blood Cancer Patients [Web]. New Delhi: Effextech. Available: http://effextech.com/health/this-new-drug-may-benefit-blood-cancer-patients/.
  4. IANS (). Novel Drug May Provide Hope for Blood Cancer Patients [Web]. New York: The Pioneer. Available: http://www.dailypioneer.com/health-and-fitness/novel-drug-may-provide-hope-for-blood-cancer-patients.html.
  5. Odisha Sun Times Editorial Desk (). Indian-Origin Researcher Discovers New Drug For Blood Cancer Patients [Web]. New York: Odisha Sun Times. Available: http://odishasuntimes.com/indian-origin-researcher-discovers-new-drug-for-blood-cancer-patients/.
  6. Press Trust of India (). New Drug to Treat Blood Cancer Developed [Web]. New York: Greater Kashmir. Available: http://www.greaterkashmir.com/news/life-style/new-drug-to-treat-blood-cancer-developed/251968.html.
  7. IANS (). Novel Drug May Provide Hope for Blood Cancer Patients [Web]. New York: BDC News. Available: http://bostondesiconnection.com/novel-drug-may-provide-hope-blood-cancer-patients/.
  8. eCancer News (). Mouse Models Show HDAC Inhibitors May Benefit Ph Leukaemia Patients [Web]. eCancer News. Available: http://ecancer.org/news/11773-mouse-models-show-hdac-inhibitors-may-benefit-ph-leukaemia-patients.php.
  9. TVN with Agency Input (). This New Drug May Benefit Blood Cancer Patients [Web]. New Delhi: True Viral News. Available: http://trueviralnews.com/this-new-drug-may-benefit-blood-cancer-patients/.
  10. University of Utah Health (). New Cancer Drug Tested in Mice May Benefit Certain Leukemia Patients [Web]. Salt lake City: Science Newsline Medicine. Available: http://www.sciencenewsline.com/news/2017061009580013.html.
  11. Health Medicine Network (). New Cancer Drug Tested in Mice May Benefit Certain Leukemia Patients [Web]. Salt Lake City: Health Medicine Network. Available: http://healthmedicinet.com/i/new-cancer-drug-tested-in-mice-may-benefit-certain-leukemia-patients/.
  12. ANI (). New Drug May Benefit Blood Cancer Patients [Web]. Washington, D.C.: Big News Network. Available: http://www.bignewsnetwork.com/news/253538103/new-drug-may-benefit-blood-cancer-patients.
  13. Punjab Tribune (). Novel Drug May Provide Hope for Blood Cancer Patients [Web]. Available: http://www.punjabtribune.com/news/32871-novel-drug-may-provide-hope-for-blood-cancer-patients.aspx.
  14. Reporter (). This New Drug May Benefit Blood Cancer Patients [Web]. New Delhi: Tip of India. Available: http://english.tipofindia.com/this-new-drug-may-benefit-blood-cancer-patients/.
  15. Abody (). New Cancer Drug Tested in Mice May Benefit Certain Leukemia Patients [Web]. Abody.
  16. SVRB (). New Cancer Drug Tested in Mice May Benefit Certain Leukemia Patients [Web]. SVRB. Available: https://svrb.net/health-and-medicine/new-cancer-drug-tested-in-mice-may-benefit-certain-leukemia-patients.html.
  17. Indias Media (). Scientists Find New Medication that Could Help Blood Cancer Patients [Web]. Washington. Available: https://www.indiasmedia.com/health-trends/scientists-find-new-medication-that-could-help-blood-cancer-patients/.
  18. The Hans India (). Hope Kindles for Blood Cancer Patients [Web]. Available: http://www.thehansindia.com/posts/index/Health/2017-06-13/Hope-kindles-for-blood-cancer-patients/306132.
  19. ANI (). New Drug May Benefit Blood Cancer Patients [Web]. Washington, D.C.: New Kerala. Available: http://www.newkerala.com/news/fullnews-248401.html.
  20. IANS (). Novel Drug May Provide Hope for Blood Cancer Patients [Web]. New York: Suryaa. Available: https://www.suryaa.com/10996-.
  21. Business Standard via NewsPoints Desk (). New Drug to Treat Blood Cancer Developed [Web]. First Word Pharma. Available: https://www.firstwordpharma.com/node/1479099.
  22. Cusabio (). Inhibiting DNA Repair Provides Therapeutic Benefits for ALL [Web]. Cusabio. Available: http://about.cusabio.com/c-20176.html.
  23. ANI (). New Drug May Benefit Blood Cancer Patients [Web]. Washington.. Available: http://www.siasat.com/news/new-drug-may-benefit-blood-cancer-patients-1198156/.
  24. Outlook The News Scroll (). New Drug to Treat Blood Cancer Developed [Web]. New York: Outlook India. Available: http://www.outlookindia.com/newsscroll/new-drug-to-treat-blood-cancer-developed/1072407.
  25. Lovrek, Joe (). New Cancer Drug Tested in Mice May Benefit Certain Leukemia Patients [Web]. Cancer News. Available: http://cancer-facts.info/?s=bhaskara.
  26. ITDK (). New Cancer Drug Tested in Mice May Benefit Certain Leukemia Patients [Web]. ITDK. Available: https://itdk.net/health-and-medicine/new-cancer-drug-tested-in-mice-may-benefit-certain-leukemia-patients.html.
  27. IANS (). Novel Drug May Provide Hope for Blood Cancer Patients [Web]. New York: Indo Asian News Service; IANS India Private Limited. Available: https://in.news.yahoo.com/novel-drug-may-hope-blood-cancer-patients-101004158.html.
  28. IANS (). Novel Drug May Provide Hope for Blood Cancer Patients [Web]. New York: India New England News. Available: http://indianewengland.com/2017/06/novel-drug-may-provide-hope-blood-cancer-patients/.
  29. Staff Writer (). Cancer News: New Cancer Drug Tested in Mice May Benefit Certain Leukemia Patients [Web]. Youth Health Mag. Available: http://www.youthhealthmag.com/articles/47140/20170612/new-cancer-drug-tested-in-mice-may-benefit-certain-leukemia-patients.htm.
  30. University of Utah Health (). New Cancer Drug Shows Promise to Treat Leukemia in Mouse Models [Web]. News Medical Life Sciences. Available: http://www.news-medical.net/news/20170609/New-cancer-drug-shows-promise-to-treat-leukemia-in-mouse-models.aspx.
  31. Press Trust of India PTI (). Indian-Origin Scientist Develops New Drug to Treat Blood Cancer [Web]. New York: Tribune India. Available: http://www.tribuneindia.com/news/health/indian-origin-scientist-develops-new-drug-to-treat-blood-cancer/420310.html.
  32. Asian News International (). Researchers Find New Drug that May Benefit Blood Cancer Patients [Web]. Hindustan Times. Available: http://www.hindustantimes.com/fitness/researchers-find-new-drug-that-may-benefit-blood-cancer-patients/story-lkI82TUlCkBJs09hy39cEO.html.
  33. MicroFinance Monitor (). Indian-Origin Scientist Finds Cure to Leukemia in Combination of Drugs [Web]. MicroFinance Monitor. Available: http://www.microfinancemonitor.com/indian-origin-scientist-finds-cure-leukemia-combination-drugs/45954.
  34. News Agencies (). New Drug May Benefit Blood Cancer Patients [Web]. Catch News. Available: http://www.catchnews.com/health-news/new-drug-may-benefit-blood-cancer-patients-64731.html.
  35. Science News (). New Cancer Drug Tested in Mice May Benefit Certain Leukemia Patients [Web]. Science Daily. Available: https://www.sciencedaily.com/releases/2017/06/170609193059.htm.
  36. IANS (). Novel Drug May Provide Hope for Blood Cancer Patients [Web]. New York: Can-India. Available: https://www.canindia.com/novel-drug-may-provide-hope-for-blood-cancer-patients/.
  37. Raphael J (). New Leukemia Drug Shows Promising Results [Web]. Nature World News. Available: http://www.natureworldnews.com/articles/38400/20170612/new-leukemia-drug-shows-promising-results.htm.
  38. Marriott N (). New Cancer Drug Tested in Mice May Benefit Certain Leukaemia Patients [Web]. Drug Target Review. Available: https://www.drugtargetreview.com/news/23806/new-leukaemia-patients/.
  39. Press Trust of India PTI (). New Drug to Treat Blood Cancer Developed in US [Web]. New York: The Hitavada. Available: http://thehitavada.com/Encyc/2017/6/11/New-drug-to-treat-blood-cancer-developed-in-US.aspx.
  40. Chinn S (). New Cancer Drug Tested In Mice May Benefit Certain Leukemia Patients [Video]. Salt Lake City: Good 4 Utah. Available: http://www.good4utah.com/news/local-news/new-cancer-drug-tested-in-mice-may-benefit-certain-leukemia-patients/740140268.
  41. Hunstman Cancer Institute at the University of Utah (). New Cancer Drug Tested In Mice May Benefit Certain Leukemia Patients [Web]. Huntsman Cancer Institute Newsroom. Available: http://huntsmancancer.org/newsroom/2017/06/new-cancer-drug-tested-in-mice-may-benefit-certain-leukemia-patients.php.
  42. University of Utah Health (). New Cancer Drug Tested in Mice May Benefit Certain Leukemia Patients [Web]. EurakAlert! and the American Association for the Advancement of Science (AAAS). Available: https://www.eurekalert.org/pub_releases/2017-06/uouh-ncd060917.php.
  43. University of Utah Health Sciences (). Why Elephants Rarely Get Cancer: Potential Mechanism Identified that May Be Key to Cancer Resistance [Web]. Medical Xpress. Available: https://medicalxpress.com/news/2015-10-elephants-rarely-cancer-potential-mechanism.html.
  44. Mudur GS (). Jumbo Shield Against Cancer [Web]. The Telegraph India. Available: https://www.telegraphindia.com/1151009/jsp/nation/story_47017.jsp.
  45. University of Utah (). Why Elephants Rarely Get Cancer [Web]. Salt Lake City: Huntsman Cancer Institute at the University of Utah. Available: http://huntsmancancer.org/newsroom/2015/10/why-elephants-rarely-get-cancer.php.
  46. Weill Cornell Medicine (). Novel Drug Shuts Down Master Protein Key to Lymphoma [Web]. Weill Cornell Medicine Newsroom. Available: http://news.weill.cornell.edu/news/2013/08/novel-drug-shuts-down-master-protein-key-to-lymphoma.
  47. MacMillan L (). Throwing a Wrench in DNA Machinery: New Cancer Drugs May Work by Interfering with Chromatin Structure [Web]. Nashville, TN: Vanderbilt Ingram Cancer Center. Available: https://news.vicc.org/2010/12/throwing-a-wrench-in-dna-machinery/.
  48. AACI Update (). New Cancer Drug Tested In Mice May Benefit Certain Leukemia Patients [Web]. Association of American Cancer Institutes. Available: http://www.aaci-cancer.org/update/2017_07update.asp.
  49. Deccan Chronicle (). Researchers Discover New Drug that Could Help Blood Cancer Patients [Web]. Washington: Dot Emirates. Available: https://www.dotemirates.com/en/details/3532814?from=dot.
  50. Vanderbilt University Medical Center (). The Good and Bad Side of Anti-Cancer Compounds [Web]. EurekAlert! and the American Association for the Advancement of Science (AAAS). Available: https://www.eurekalert.org/pub_releases/2008-04/vumc-tga041008.php.
  51. Marino M (). Study Examines Good, Bad Sides of Anti-Cancer Agents [Web]. Vanderbilt University School of Medicine. Available: https://medschool.vanderbilt.edu/hiebert-lab/research-news/study-examines-good-bad-sides-anti-cancer-agents.