My clinical and scientific research contributed to better understanding the mechanisms of resistance to monoclonal antibodies targeting CD20 in B-cell lymphoma, development of novel therapeutic strategies for patients with relapsed/refractory B-cell lymphomas, and to the identification of biomarkers of response to targeted agents. Our group of investigators is actively involved in clinical, translational and laboratory-based research projects, in an attempt to gain a better understanding of pathogenesis, prognostic factors, and cellular/molecular features associated with the development of “resistance” in these lymphoid neoplasms. Our research focuses in 1) improving the biological activity of monoclonal antibodies against b-cell lymphoma; 2) overcoming rituximab-chemotherapy resistance in b-cell lymphoma; 3) evaluate novel small molecule inhibitors targeting key-regulatory pathways in lymphomas; 4) identification of biomarkers of response to currentlycurrent available therapies in patients with B-cell lymphoma; and 5) applying our pre-clinical work in the rational design of clinical trials for patients with lymphomas.
Our group set up and developed the translational research lymphoma program based primarily on the use of targeted treatment of lymphoma. We have several laboratory projects that can be divided in two group: 1) projects related to understanding the mechanisms of rituximab-chemotherapy resistance in B-cell malignancies and 2) projects focused in developing novel therapeutic strategies for patients with B-cell lymphomas. Our current work centers in the following objectives:
• Improving the biological activity of monoclonal antibodies against B-cell lymphomas:
• Overcoming rituximab-chemotherapy resistance in B-cell lymphoma:
Targeting rituximab resistant B-cell lymphomas with low surface CD20 levels.
Altering the balance of Bcl-2 family members levels using BH3 mimetics, inhibitory of apoptosis proteins (IAP) inhibitors and/or histone deacetylase (HDAC) inhibitors.
Restoring the apoptotic threshold to chemotherapy drugs by blocking the ubiquitin-proteasome system (UPS).
Targeting hexokinase II (HKII)-VDAC complex in rituximab-resistant lymphoma
• Identification of biomarkers of response to current available therapies in patients with B-cell lymphoma:
- Juan Gu, Ph.D. Translational Research Scientist
- Cory Mavis, Sr. Research Specialist
- Thomas Ippolito, Research Specialist
- Pallawi Torka, MD
Gerson JN, Handorf E, Villa D, Gerrie AS, Chapani P, Li S, Medeiros LJ, Wang MI, Cohen JB, Calzada O, Churnetski MC, Hill BT, Sawalha Y, Hernandez-Ilizaliturri FJ, Kothari S♦, Vose JM, Bast MA, Fenske TS, Narayana Rao Gari S, Maddocks KJ, Bond D, Bachanova V, Kolla B, Chavez J, Shah B, Lansigan F, Burns TF, Donovan AM, Wagner-Johnston N, Messmer M, Mehta A, Anderson JK, Reddy N, Kovach AE, Landsburg DJ, Glenn M, Inwards DJ, Karmali R, Kaplan JB, Caimi PF, Rajguru S, Evens A, Klein A, Umyarova E, Pulluri B, Amengual JE, Lue JK, Diefenbach C, Fisher RI, Barta SK. Survival Outcomes of Younger Patients With Mantle Cell Lymphoma Treated in the Rituximab Era. J. Clin Oncol 37:1-9; 2019. PMID: 30615550.
Akhtar OS♦, Attwood K, Lund I, Hare R, Hernandez-Ilizaliturri FJ, Torka P. Dose reductions in ibrutinib therapy are not associated with inferior outcomes in patients with chronic lymphocytic leukemia (CLL). Leuk Lymphoma. Jan 2:1-6. doi: 10.1080/10428194.2018.1554862. [Epub ahead of print]. 2019 PMID: 30601100.
Runckel K^, Barth MJ, Mavis C, Gu JJ, Hernandez-Ilizaliturri FJ. The SMAC mimetic LCL-161 displays antitumor activity in preclinical models of rituximab-resistant B-cell lymphoma. Blood Adv. 2:3516-3525; 2018. PMID: 30530779.
Badar T, Hamadani M, Bachanova V, Maddocks KJ, Umyarova E, Chavez JC, Epperla N, Chhabra S, Xavier AC, Karmali R, Salhab M, Reddy N, Glenn MJ, Hernandez-Ilizaliturri FJ, Flowers CR, Evens AM, Zhou Z, Lansigan F, Barta SK, Cohen JB, Fenske TS, Costa LJ. Efficacy of salvage chemotherapy in diffuse large B cell lymphoma with primary treatment failure according to putative cell of origin. Leuk Lymphoma. 2:1-7; 2018. PMID: 30277110.
Etter JL, Cannioto R, Soh KT, Alquassim E, Almohanna H, Dunbar Z, Joseph JM, Balderman S, Hernandez-Ilizaliturri FJ, Moysich KB. Lifetime physical inactivity is associated with increased risk for Hodgkin and non-Hodgkin lymphoma: A case-control study. Leuk Res 69:7-11, 2018. PMID: 29609041
Bhatti M, Ippolito T, Mavis C, Gu J§, Gairo MS, Lim MS, Hernandez-Ilizaliturri F, Barth MJ. Pre-clinical activity of targeting the PI3K/Akt/mTOR pathway in Burkitt Lymphoma. Ontotarget 9(31):21820-21830, 2018. PMID: 29774105
Rohl R, Bax D, Schierer S, Bogner PN, Hernnadez-Ilizaliturri F, Paragh G. A Case for histologic verification of the diagnosis of atypical psoriasis before systemic therapy. JAAD Case Rep 4(5):465-467, 2018.
Hoppe RT, Advani RH, Ai WZ, Ambinder RF, Aoun P, Armand P, Bello CM, Benitz CM, Bierman PJ, Chen R, Dabaja B, Dean R, Forero A, Gordon LI, Hernandez-Ilizaliturri FJ, Hochberg EP, Huang J, Johnson PB, Kaminski MS, Kenkre VP, Khan N, Maddocks K, Maloney DG, Metzger M, Moore JO Morgan D, Moskowitz CH, Mulroney C, Rabinovitch R, Seropian S, Tao R, Winter JN, Yahalom J, Burns JL, Ogba N. J Natl Compr Canc Netw 16(3):245-254, 2018. PMID: 29523663
Vachhani P♦, Neppalli VT, Cancino CJ, Bogner P, Roche CL, Paragh G, Grassi MA, Hernandez-Ilizaliturri FJ. Radiographical imaging and bone marrow biopsy in staging of cutaneous B-ceoll lymphoma. Br J Haematol 2018. doi: 10.1111/bjh.15154. [Epub ahead of print] PMID: 29468663 Role: Data analysis and interpretation; manuscript revision; final approval of manuscript.
Gu JJ§, Singh A♦, Xue K♦, Mavis C, Barth M, Yanamadala V, Lenz P, Grau M, Lenz G, Czuczman MS, Hernandez-Ilizaliturri FJ. Up-regulation of hexokinase II contributes to rituximab-chemotherapy resistance and is a clinically relevant target for therapeutic development. Oncotarget. 9: 4020-33, 2018. PMID: 29423101
Torka P, Patel P, Tan W, Wilding G, Bhat SA, Czuczman MS, Lee KP, Deeb G, Neppalli V, Mavis C, Wallace P, Hernandez-Ilizaliturri FJ. A Phase II trial of rituximab combined with pegfilgrastim in patients with indolent B-cell non-Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk. 18(1):e51-e60, 2018. PMID: 29233743
Pilchowska M, Pittaluga S, Ferry JA, Chang H, Kanakry JA, Sehn LH, Feldman T, Abramson JS, Kritharis A, Hernandez-Ilizaliturri FJ, Lossos IS, Press OW, Fenske TS, Friedberg JW, Vose JM, Blum KA, Jagadeesh D, Woda B, Gupta GK, Gascoyne RD, Jaffe ES, Evens AM. Clinicopathologic consensus study of gray zone lymphoma with features intermediate between DLBCL and classical HL. Blood AV 1(26):2600-2609, 2017. PMID: 29296913
Winter AM, Landsburg DJ, Mato AR, Isaac K, Hernandez-Ilizaliturri FJ, Reddy N, Smith S, Shadman M, Smith MR, Caimi P, Jagadesh D, Hill BT. A multi-international outcomes analysis of patients with relapsed or refractory DLBCL treated with ibrutinib. [Epub ahead of print] doi:10.1182/blood-20217-05-786988. Blood 130:1676-1679, 2017. PMID: 28794071