Zahid Hussain Siddik, Ph.D.
Department of Experimental Therapeutics, Division of Cancer Medicine
Present Title & Affiliation
Primary Appointment
Professor of Medicine (Pharmacology), Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Research Interests
Presence of wild-type p53 is prevalent in many refractory cancers. My current interests are focused on understanding how drug resistance is induced when wild-type p53 is present and how such a mechanism can be circumvented through drug design. More specifically, we are focused on the dysfunctionality of the p53/p21 pathway and how it impacts apoptosis through loss of checkpoint response.
Education & Training
Degree-Granting Education
| 1975 | University of London, London, USA, PHD, Biochemistry |
| 1972 | University of Liverpool, Liverpool, GBR, BS, Biochemistry |
Postgraduate Training
| 1976-1980 | Fogarty Postdoctoral Fellow, Laboratory of Toxicology, Drug Interactions Section, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, MD |
| 1972-1975 | Postgraduate Student, Biochemistry Department, St. Mary's Hospital Medical School, Paddington, London W2 1PG |
Selected Publications
Peer-Reviewed Articles
- Bhatt M, Ivan C, Xie X, Siddik ZH. Drug-dependent functionalization of wild-type and mutant p53 in cisplatin-resistant human ovarian tumor cells. Oncotarget 8(7):10905-10918, 2017. PMID: 28038466.
- Altaf M, Monim-Ul-Mehboob M, Kawde AN, Corona G, Larcher R, Ogasawara M, Casagrande N, Celegato M, Borghese C, Siddik ZH, Aldinucci D, Isab AA. New bipyridine gold(III) dithiocarbamate-containing complexes exerted a potent anticancer activity against cisplatin-resistant cancer cells independent of p53 status. Oncotarget 8(1):490-505, 2017. PMID: 27888799.
- Thiabaud G, McCall R, He G, Arambula JF, Siddik ZH, Sessler JL. Activation of Platinum(IV) Prodrugs By Motexafin Gadolinium as a Redox Mediator. Angew Chem Int Ed Engl 55(41):12626-31, 2016. e-Pub 2016. PMID: 27377046.
- Xie X, Lozano G, Siddik ZH. Heterozygous p53V172F mutation in cisplatin-resistant human tumor cells promotes MDM4 recruitment and decreases stability and transactivity of p53. Oncogene 35(36):4798-4806, 2016. PMID: 26876197.
- Tsimberidou AM, Said R, Culotta K, Wistuba I, Jelinek J, Fu S, Falchook G, Naing A, Piha-Paul S, Zinner R, Siddik ZH, He G, Hess K, Stewart DJ, Kurzrock R, Issa JP. Phase I study of azacitidine and oxaliplatin in patients with advanced cancers that have relapsed or are refractory to any platinum therapy. Clin Epigenetics 7(1):29, 2015. e-Pub 2015. PMID: 25806091.
- Kim ES, Tang X, Peterson DR, Kilari D, Chow CW, Fujimoto J, Kalhor N, Swisher SG, Stewart DJ, Wistuba II, Siddik ZH. Copper transporter CTR1 expression and tissue platinum concentration in non-small cell lung cancer. Lung Cancer 85(1):88-93, 2014. e-Pub 2014. PMID: 24792335.
- Thiabaud G, Arambula JF, Siddik ZH, Sessler JL. Photoinduced reduction of Pt(IV) within an anti-proliferative Pt(IV)-texaphyrin conjugate. Chemistry 20(29):8942-7, 2014. e-Pub 2014. PMID: 24961491.
- Preihs C, Arambula JF, Magda D, Jeong H, Yoo D, Cheon J, Siddik ZH, Sessler JL. Recent Developments in Texaphyrin Chemistry and Drug Discovery. Inorg Chem 52(21):12184-12192, 2013. e-Pub 2013. PMID: 23557113.
- He G, Kuang J, Koomen J, Kobayashi R, Khokhar AR and Siddik ZH. Recruitment of trimeric proliferating cell nuclear antigen by G1-phase cyclin-dependent kinases following DNA damage with platinum-based antitumor agents. Br J Cancer 109(9):2378-88, 2013. PMID: 24104967.
- Moreno-Smith M, Halder JB, Meltzer PS, Gonda TA, Mangala LS, Rupaimoole R, Lu C, Nagaraja AS, Gharpure KM, Kang Y, Rodriguez-Aguayo C, Vivas-Mejia PE, Zand B, Schmandt R, Wang H, Langley RR, Jennings NB, Ivan C, Coffin JE, Armaiz GN, Bottsford-Miller J, Kim SB, Halleck MS, Hendrix MJ, Bornman W, Bar-Eli M, Lee JS, Siddik ZH, Lopez-Berestein G, Sood AK. ATP11B mediates platinum resistance in ovarian cancer. J Clin Invest 123(5):2119-30, 2013. e-Pub 2013. PMID: 23585472.
- Moreno-Smith M, Lee SJ, Lu C, Nagaraja AS, He G, Rupaimoole R, Han HD, Jennings NB, Roh JW, Nishimura M, Kang Y, Allen JK, Armaiz GN, Matsuo K, Shahzad MM, Bottsford-Miller J, Langley RR, Cole SW, Lutgendorf SK, Siddik ZH, Sood AK. Biologic effects of dopamine on tumor vasculature in ovarian carcinoma. Neoplasia 15(5):502-10, 2013. PMID: 23633922.
- Kim ES, Lee JJ, He G, Chow CW, Fujimoto J, Kalhor N, Swisher SG, Wistuba II, Stewart DJ, Siddik ZH. Tissue platinum concentration and tumor response in non-small-cell lung cancer. J Clin Oncol 30(27):3345-52, 2012. e-Pub 2012. PMID: 22891266.
- Martinez-Rivera M, Siddik ZH. Resistance and gain-of-resistance phenotypes in cancers harboring wild-type p53. Biochem Pharmacol 83(8):1049-62, 2012. e-Pub 2011. PMID: 22227014.
- Arambula JF, Sessler JL, Siddik ZH. A texaphyrin-oxaliplatin conjugate that overcomes both pharmacologic and molecular mechanisms of cisplatin resistance in cancer cells. Medchemcomm 3(10):1275-1281, 2012. PMID: 23936624.
- Le XF, Mao W, He G, Claret FX, Xia W, Ahmed AA, Hung MC, Siddik ZH, Bast RC. The role of p27(Kip1) in dasatinib-enhanced paclitaxel cytotoxicity in human ovarian cancer cells. J Natl Cancer Inst 103(18):1403-22, 2011. e-Pub 2011. PMID: 21813412.
- He G, Kuang J, Khokhar AR, Siddik ZH. The impact of S- and G2-checkpoint response on the fidelity of G1-arrest by cisplatin and its comparison to a non cross-resistant platinum (IV) analog. Gynecol Oncol 122(2):402-409, 2011. e-Pub 2011. PMID: 21592546.
- Arambula JF, Sessler JL, Siddik ZH. Overcoming biochemical pharmacologic mechanisms of platinum resistance with a texaphyrin-platinum conjugate. Bioorg Med Chem Lett 21(6):1701-5, 2011. e-Pub 2011. PMID: 21345675.
- Preihs C, Arambula JF, Lynch VM, Siddik ZH, Sessler JL. Bismuth- and lead-texaphyrin complexes: towards potential a-core emitters for radiotherapy. Chem Commun (Camb) 46(42):7900-2, 2010. e-Pub 2010. PMID: 20922235.
- Kurokawa T, He G, Siddik ZH. Protein kinase inhibitors emodin and dichloro-ribofuranosylbenzimidazole modulate the cellular accumulation and cytotoxicity of cisplatin in a schedule-dependent manner. Cancer Chemother Pharmacol 65(3):427-36, 2010. e-Pub 2009. PMID: 19529937.
- Rowe RW, Strebel FR, Proett JM, Deng W, Chan D, He G, Siddik Z, Bull JM. Fever-range whole body thermotherapy combined with oxaliplatin: A curative regimen in a pre-clinical breast cancer model. Int J Hyperthermia 26(6):565-576, 2010. e-Pub 2010. PMID: 20707651.
- Arambula JF, Sessler JL, Fountain ME, Wei WH, Magda D, Siddik ZH. Gadolinium Texaphyrin (Gd-Tex)-Malonato-Platinum Conjugates: Synthesis and Comparison with Carboplatin in Normal and Pt-Resistant Cell Lines. Dalton Trans(48):10834-40, 2009. e-Pub 2009. PMID: 20023913.
- Mangala LS, Zuzel V, Schmandt R, Leshane ES, Halder JB, Armaiz-Pena GN, Spannuth WA, Tanaka T, Shahzad MM, Lin YG, Nick AM, Danes CG, Lee JW, Jennings NB, Vivas-Mejia PE, Wolf JK, Coleman RL, Siddik ZH, Lopez-Berestein G, Lutsenko S, Sood AK. Therapeutic Targeting of ATP7B in Ovarian Carcinoma. Clin Cancer Res 15(11):3770-80, 2009. e-Pub 2009. PMID: 19470734.
Invited Articles
- Siddik ZH. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 22(47):7265-79, 2003. PMID: 14576837.
Abstracts
- He G, Kuang J, Kommen J, Kobayashi R, Khokhar AR, ZH Siddik. DNA damage by platinum-based drugs induces P21-dependent recruitment of PCNA as a homotrimer into the inhibited G-1 phase CDK complex. Proc. Am Assoc Cancer Res, 2011.
- He G, Kuang J, Khokhar AR, Siddik ZH. The underlying basis for divergent cell cycles kinetics following checkpoint activation by cisplatin and a platinum (IV) analog. Am Assoc Cancer Res 51, 2010.
- Meraz IM, Khokhar A, Siddik ZH. Defective Check Point Kinase 2 (Chk2) Expression in Cisplatin-resistant Ovarian Tumor Cells Impedes wild-type P53 function. Proc. Am. Assoc. Cancer Res 51, 2010.
- Huang Z, He G, Khokhar A, Siddik ZH. Paradoxical molecular changes in cisplatin-resistant ovarian tumor cells: up-regulation of drug-sensitizing and down-regulation of resistance-inducing genes. Proc Am Assoc Cancer Res 50, 2009.
Book Chapters
- Siddik ZH. Targeting p21-dependent pathways for cell death in cancer therapy. In: Checkpoint Controls and Targets in Cancer Therapy. Humana Press: New Jersey, 199-213, 2010.
- Siddik ZH. Drug resistance and the tumor suppressor p53: The paradox of wild-type genotype in chemorefractory cancers. In: Drug Resistance in Cancer Cells. Humana Press: New Jersey, 209-231, 2009.
Books (edited and written)
- Boonstra J, Bunz F, Kuang J, Kramer A, Xiong Y, Lee MH, Nakanishi M, Alao JP, Lozano G, Giordano A, Friedenson B, Kaina B, Pevarello P, Eastman A, Siddik ZH, Bast R, Zhang H, Taylor SS, Rudolph J. Checkpoint Controls and Targets in Cancer Therapy. Ed(s) ZH Siddik. Humana Press: New Jersey, 2010.
- Bates S, Fidler IJ, Kondo Y, Reddy EP, Mehta K, Hodkinson PS, Huang P, Aggarwal BB, Siddik ZH, Ali-Osman F, Ozoplat B, Calin G, Troester M, Price P, Chan MM. Drug Resistance in Cancer Cells. Ed(s) K Mehta, ZH Siddik. Humana Press: New Jersey, 2009.
Grant & Contract Support
| Title: | Phase I Clinical Trials of Anticancer Agents |
| Funding Source: | NIH/NCI |
| Role: | Co-Investigator |
| Title: | Pharmacology of Carboplatin in Combination with RMP-7 in the Treatment of Malignant Glioma in a Phase II Study |
| Funding Source: | Alkermes, Inc |
| Role: | Principal Investigator |
| Title: | Correlated Laboratory - Clinical Phase I Drug Development |
| Funding Source: | NCI |
| Role: | Co-Investigator |
| Title: | c-erbB-2 Overexpression and Platinum Activity in Refractory Ovarian Tumors |
| Funding Source: | Sandra G Davis Ovarian Cancer Research Fund |
| Role: | Principal Investigator |
| Title: | JAB1 as a Marker for Anticancer Drug Resistance |
| Funding Source: | UTMDACC PRS |
| Role: | Co-Investigator |
| Title: | Mechanistic Development of Platinum-Based Drugs |
| Funding Source: | NCI |
| Role: | Principal Investigator |
| Title: | Circumvention of Cisplatin Resistance |
| Funding Source: | NCI |
| Role: | Principal Investigator |
| Title: | Therapy of Breast Tumor Cells Overexpressing c-erbB-2/neu |
| Funding Source: | Department of Defense Breast Cancer Research Program |
| Role: | Principal Investigator |
| Title: | Training for Academic Oncology |
| Funding Source: | NCI-NIH |
| Role: | Mentor |
| Title: | Clinical Oncology Career Development Program |
| Funding Source: | NIH |
| Role: | Mentor |
| Title: | Development of DACH-acetato-Pt for an IND Application |
| Funding Source: | MDACC CTDP Kleberg Drug Development Grant |
| Role: | Co-Principal Investigator |
| Title: | Effects of DNA Damaging Agents on G2 Phase Checkpoint |
| Funding Source: | NIH/NCI |
| Role: | Co-Investigator |
| Title: | Phase II/III Clinical Trials of Anticancer Agents |
| Funding Source: | NCI |
| Role: | Co-Investigator |
| Title: | Training for Academic Oncology |
| Funding Source: | NCI-NIH |
| Role: | Mentor |
| Title: | Pharmacology and New Drug Development, CCSG Core Grant |
| Funding Source: | NIH/NCI |
| Role: | Co-Program Leader |
| Title: | Training of Academic Gynecologic Oncologists |
| Funding Source: | NIH/NCI |
| Role: | Mentor |
| Title: | Targeted Development of Platinum Drugs |
| Funding Source: | NIH/NCI |
| Role: | Principal Investigator |
| Title: | Rewiring the MDM4 Circuitry to Activate p53 in Chemoresistant Tumor Cells |
| Funding Source: | Cancer Prevention & Research Institute of Texas (CPRIT) |
| Role: | Principal Investigator |
| Title: | Targeting MDM4 in Chemoresistant Cancers |
| Funding Source: | NIH/NCI |
| Role: | Principal Investigator |
Patient Reviews
CV information above last modified February 13, 2024