Harrison College of Pharmacy

Current Funding

Novel inhibitor for oncogenic RAS for lung cancer
Funder: NIH/NCI 1R01CA254197-01
Date: 2021-26
Role: Co-Investigator
Description: The long-term goals are to better understand mechanism of action, identify a drug development candidate for IND-enabling safety assessment and establish a mechanistic rationale to select patients for clinical trials based on activated RAS levels.
Scored in 2nd percentile

Novel sulindac derivatives targeting cGMP signaling to enhance cancer immunotherapy
Funder: NIH/NCI 1 R01CA238514-01
Date: 2020-25
Role: Co-Investigator
Description: This proposal will synthesize and characterize a novel series of non-COX inhibitory sulindac derivatives using prototype derivatives that target PDE5 and/or PDE10, while optimizing drug-like properties to increase systemic exposure.

Phosphodiesterase 10A, a novel target for lung cancer chemoprevention
Funder: NIH/NCI 5 R01 CA197147-04
Date: 2016-23
Role: Co-Investigator
Description: This project will synthesize and design a novel group of sulindac derivatives relating to a drug development candidate, MCI-048, that contain a methyl-pyrrolidene substitution for lung cancer by targeting phosphodiesterase 10 and to evaluate their efficacy, safety, and mechanism of action using in vitro and in vivo models. Additional aims are to study the involvement of PDE10 in lung tumorigenesis and to study additional analogs.

A Novel Non-COX inhibitory Sulindac Derivative for Colorectal Cancer Chemoprevention with Selective PDE10 and Wnt/β-Catenin Inhibitory Activity
Funder: NIH via Fox Chase Cancer Center
Date: 2018-2021
Role: Sub-contract Co-Investigator
Description: Use a panel of biomarkers to assess chemopreventive activity of a novel PDE10 inhibitor.

A Novel beta-Catenin Blocker That Activates Antitumor Immunity For Breast Cancer
Funder: Breast Cancer Research Foundation Alabama
Date: 2021-22
Role: Co-Investigator
Description: The purpose of this project is to evaluate a novel PDE10 inhibitor for breast cancer in a mouse model of metastatic disease.

Research Interests

• NCBI MyBibliography

I have a broad background in pharmacology and toxicology with expertise in drug discovery and development of anticancer compounds and cancer chemoprevention research.  I started my career at Southern Research Institute (Birmingham, AL) and over the next 16 years I was responsible for scientific oversight for all in vivo anticancer testing performed at the institute on a contract basis (300+ studies annually).  I was involved in establishment and in vivo propagation of a collection of over 80 human (both cell and patient-derived) and mouse tumor xenograft models and management of animal and formulation laboratories.

I provided guidance and served as a study director on over 1,100 in vivo pharmacology studies to advance drug candidates (discovered in-house and for commercial sponsors) into clinical development with 4 candidates subsequently receiving the FDA approval [Halaven® (for the treatment of metastatic breast cancer), Nexavar® (for the treatment of hepatocellular and renal cell carcinoma), Clolar® (for the treatment of pediatric refractory acute lymphoblastic leukemia), and Tysabri® (for the treatment of relapsing forms of multiple sclerosis)].

Next, at Biscayne Pharmaceuticals Inc. I lead the preclinical development of the company’s lead anticancer compound discovered by Dr. Andrew V. Schally, a Nobel Prize laureate and pioneering endocrine drug developer.  I was responsible for directing preclinical CROs in the conduct of the IND-directed studies (including efficacy, safety toxicology, pharmacokinetics, and bioanalytical studies.  Once I entered academia, first at the University of South Alabama and now at Harrison College of Pharmacy, I was responsible for the design, formulation, conduct, data analysis, and review of all animal studies to support the efforts of Drs. Piazza, Keeton, and Chen to develop RAS and PDE10 inhibitors for the treatment of cancer

Selected Publications

RAS-related publications

• Coley A.B., Ward A., Keeton A.B., Chen X., Maxuitenko Y., Prakash A., Li F., Foote J.B., Buchsbaum D.J., and Piazza G.A. (2021).  “Pan-RAS inhibitors: Hitting multiple RAS isozymes with one stone”.  Advances in Cancer Research, Academic Press.  ISSN 0065-230X.
• Ward A.B, Keeton A.B., Chen X., Mattox T.E., Coley A.B., Maxuitenko Y.Y., Buchsbaum D.J., Randall T.D., Zhou G., and Piazza G.A. (2020) “Enhancing anticancer activity of checkpoint immunotherapy by targeting RAS”. MedComm. 1, 121-128.
• Mattox T.E., Chen X., Maxuitenko, Y.Y., Keeton, A.B. and Piazza G.A. (2020) “Exploiting RAS nucleotide cycling as a strategy for drugging RAS-driven cancer”. In Progress and Challenges with Inhibition of K-Ras GTPase in Cancer, International Journal Molecular Sciences, 21(1): 141. PMID: 31878223; PMCID: PMC6982188.

PDE10-related publications

• Lee, K., J., Chang, W., Ramirez-Alcantara, V.,  Chen, X., Valiyaveettil, J., Gavin, E., Musiyenko, A., Madeira da Silva, L., Annamdevula, N.S., Leavesley, S.J.,  Ward, A., Mattox, T., Wierzbicki, A., Salter, A., Lindsey, A. S., Andrews, J., Zhu, B., Wood, C., Neese, A., Nguyen, A., Berry, K., Maxuitenko, Y.,  Moyer, M. P., Gorman, G., Coward, L., Keeton, A.B., Cooper, H., Clapper, M., and G. A. Piazza (2021) “PDE10 inhibition selectively blocks Wnt/β-catenin signaling to suppress colon tumorigenesis”.  Accepted for publication 9/21/2021, Cancer Prevention Research (Featured on cover).
• Piazza G.A., Ward A., Chen X., Maxuitenko Y., Coley A., Aboelella N.S., Buchsbaum D.J., Boyd M.R., Keeton A.B., and Zhou G. (2020) “PDE5 and PDE10 inhibition activate cGMP/PKG signaling to block Wnt/β-catenin transcription, cancer cell growth, and tumor immunity” Drug Discovery Today 25: 1521-27.

Preclinical drug development

• Yulia Y. Maxuitenko, Norman L. Block, Andrew V. Schally, Samuel J. Reich, Peter Goldstein.  Preclinical development of BIS-1602, first in class growth hormone releasing hormone antagonist. (2014).  European Journal of Cancer, Vol. 50, p107.
• Carter, C.A., Chen, C., Brink, C., Vincent, P., Maxuitenko, Y. Y., Gilbert, K. S., Waud, W. R., Zhang, X. (2007).  Sorafenib is efficacious and tolerated in combination with cytotoxic or cytostatic agents in preclinical models of human non-small cell lung carcinoma. Cancer Chemother. Pharmacol. 59 (2): 183-195. PMID: 16724239.
• Rashida A. Karmali, Yulia Maxuitenko, Greg Gorman. Comparative Response of SC CAKI-1 Renal Tumor to Treatment with Doxorubicin HCl and Doxorubicin Orotate. (2014).  Journal of Cancer Therapy 5: 427-441. http://dx.doi.org/10.4236/jct.2014.55049

Drug Discovery

• Emmanouilidi A., Ruban E., Casari I., Akkaya B.G., Maffucci T., Furic L., Guffanti F., Broggini M., Chen X., Maxuitenko Y., Keeton A, Piazza G.A., Linton K.J. and Falasca M. (2020) “Inhibition of the lysophosphatidylinositol transporter ABCC1 reduces prostate cancer cell growth and sensitizes to chemotherapy” Cancers 12: 2022-41.
• Adamska, A., Domenichini, A., Capone, E., Damiani, V., Akkaya, BG, Linton, KJ, Di Sebastiano, P., Chen, X., Keeton, AB, Ramirez-Alcantara, V., Maxuitenko, Y., Piazza, GA, De Laurenzi, V., Sala, G., and M. Falasca (2019) “Pharmacological inhibition of ABCC3 slows tumour progression in animal models of pancreatic cancer” Journal of Experimental & Clinical Cancer Research 38: 7-14.
• Abdel-Halim M., Sigler S., Racheed N.A., Hammam M.A., Hefnawy A.M., Fathalla R.K., Maher A., Maxuitenko Y., Keeton A.B., Hartmann R.W., Engel M., Piazza, G.A. and Abadi A.H. (2021) “From celecoxib to a novel class of phosphodiesterase 5 Inhibitors: Trisubstituted pyrazolines as novel phosphodiesterase 5 inhibitors with extremely high potency and PDE isozyme selectivity”. J. Med Chem. 64, 8, 4462–4477.
• Thottassery JV, Sambandam V, Allan PW, Maddry JA, Maxuitenko YY, Tiwari K, Hollingshead M, Parker, W. Novel DNA methyltransferase-1 (DNMT1) depleting anticancer nucleosides, 4’-thio-2’-deoxycytidine and 5-aza-4’-thio-2’-deoxycytidine. (2014).  Cancer Chemother. Pharmacol. 74:291-302. PMID: 24908436, PMCID: PMC4194194.
• Coburn M.A., Brueggemann S., Bhatia S., Cheng B., Li B.D., Li X.L., Luraguiz N., Maxuitenko Y.Y., Orchard E.A., Zhang S., Stoff-Khalili M.A., Mathis J.M., Kleiner-Hancock H.E.  Establishment of a mammary carcinoma cell line from Syrian hamsters treated with N-methyl-N-nitrosourea. (2011).  Cancer Lett. 312(1): 82-90. PMID: 21893382 PMCID: PMC3185182.
• Qu Z, Van Ginkel S, Roy AM, Westbrook L, Nasrin M, Maxuitenko Y, Frost AR, Carey D, Wang W, Li R, Grizzle WE, Thottassery JV, Kern FG. Vascular endothelial growth factor reduces tamoxifen efficacy and promotes metastatic colonization and desmoplasia in breast tumors. Cancer Res. 2008 Aug 1;68(15):6232-40. doi: 10.1158/0008-5472.CAN-07-5654. PubMed PMID: 18676847; PubMed Central PMCID: PMC4337242.