
Justin M. Balko, Pharm.D., Ph.D.
- Leader, Breast Cancer Research Program
- Ingram Associate Professor of Cancer Research
- Associate Professor of Medicine (Hematology/Oncology)
Phone
777 Preston Research Building
Nashville, TN 37232-6307
Justin M. Balko, Pharm.D., Ph.D.
- Leader, Breast Cancer Research Program
- Ingram Associate Professor of Cancer Research
- Associate Professor of Medicine (Hematology/Oncology)
615-936-1495
justin.balko@vumc.org
777 Preston Research Building
Nashville, TN 37232-6307
Research Program
Departments/Affiliations
Profile
Our laboratory focuses on the discovery genomic mechanisms of therapeutic sensitivity and resistance in breast cancers and some other types of carcinomas. We have interest in identifying ways to treat basal-like, triple negative, and inflammatory breast cancer using novel molecularly targeted therapeutics and combinations of these inhibitors to circumvent drug resistance.
Specifically, our ongoing projects include 1) Understanding the role of loss of the tumor suppressor DUSP4, a negative regulator of the MAPK pathway in breast cancer;2) Molecularly targeting tumors with amplification of JAK2 and neighboring genes; and 3) Discovering new ways to target the residual disease and micrometastatic component of TNBCs that do not respond completely to neoadjuvant (pre-surgical)chemotherapy.
Education
- Pharm.D., State University of New York at Buffalo
- Ph.D., University of Kentucky, Department of Pharmaceutical Sciences
Research Emphasis
Translational cancer research with focuses on molecular therapeutics, onco-immunology and bioinformatics
Research Description
Our laboratory is focused on improving treatment outcomes in breast cancer (particularly triple-negative breast cancer) as well as in other solid tumors through translational approaches. To accomplish this, we integrate data from genomic and molecular profiling studies with molecular biology and signal transduction methodologies to identify altered pathways in cancer, the functional consequences of these alterations, and ways to directly target them in patients to improve clinical outcomes and survival. These efforts span in silico (publicly available databases), in vitro (cell culture), in vivo (mouse and human clinical studies) and in situ (histology) methods.
There are several primary focuses of the laboratory:
1) How do tumor cells evade the immune system in cancer, and how can we target these mechanisms?
We have a strong interest in the intersection between new immunotherapies and tumor cell signaling pathways. We have identified several molecular pathways that are hijacked by tumor cells in order to suppress antigen presentation, which is required for effective immunologic elimination of tumor cells. Pharmacological inhibition of these pathways can restore antigen presentation, and potentiate anti-tumor immunity. However, the mechanisms by which tumor cells evade the immune system are largely unknown. The goal of this focus is to identify these mechanisms and validate approaches to inhibit them for the benefit of patients.
2) What molecular features or biomarkers can identify patients most likely to benefit from immunotherapy?
Immunotherapies have the potential to transform cancer therapy, but not all patients respond, and these drugs are incredibly costly and not without their toxicities (see #3). Thus, identifying patients most likely to benefit from immunotherapy early on, or a priori, could be incredibly valuable in triaging patients unlikely to respond to other therapies from which they are more likely to derive benefit. The discovery of molecular markers of response to immunotherapies is a major focus of the laboratory. We recently identified competence in class-II antigen presentation as a major predictor of outcome in patients treated with anti-PD-1 therapy, and are now exploring the functionality of MHC-II expression as a mediator of anti-tumor immunity.
3) What causes autoimmune-like toxicities in patients treated with immunotherapy?
As mentioned above, immunotherapies have the potential to cause rare, but severe toxicities, sometimes resulting in treatment-related mortality. Understanding the mechanisms behind immunotherapy-induced autoimmunity and the molecular features of patients who exhibit them is critical area of need. Through high level molecular profiling of peripheral blood, tumors, and immune-related adverse event-affected organs, we hope to uncover hints as to why some patients exhibit these toxicities, and try to model these toxicities in the laboratory.
Publications
- Hanna A, Nixon MJ, Estrada MV, Sanchez V, Sheng Q, Opalenik SR, Toren AL, Bauer J, Owens P, Mason FM, Cook RS, Sanders ME, Arteaga CL, Balko JM. Combined Dusp4 and p53 loss with Dbf4 amplification drives tumorigenesis via cell cycle restriction and replication stress escape in breast cancer. Breast Cancer Res. 2022 Jul 7/18/2022; 24(1): 51. PMID: 35850776, PMCID: PMC9290202, PII: 10.1186/s13058-022-01542-y, DOI: 10.1186/s13058-022-01542-y, ISSN: 1465-542X.
- Lee KM, Lin CC, Servetto A, Bae J, Kandagatla V, Ye D, Kim G, Sudhan DR, Mendiratta S, González Ericsson PI, Balko JM, Lee J, Barnes S, Malladi VS, Tabrizi S, Reddy SM, Yum S, Chang CW, Hutchinson KE, Yost SE, Yuan Y, Chen ZJ, Fu YX, Hanker AB, Arteaga CL. Epigenetic Repression of STING by MYC Promotes Immune Evasion and Resistance to Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer. Cancer Immunol Res. 2022 Jul 7/1/2022; 10(7): 829-43. PMID: 35561311, PMCID: PMC9250627, PII: 698905, DOI: 10.1158/2326-6066.CIR-21-0826, ISSN: 2326-6074.
- Johnson DB, Nebhan CA, Moslehi JJ, Balko JM. Immune-checkpoint inhibitors: long-term implications of toxicity. Nat Rev Clin Oncol [print-electronic]. 2022 Apr; 19(4): 254-67. PMID: 35082367, PMCID: PMC8790946, PII: 10.1038/s41571-022-00600-w, DOI: 10.1038/s41571-022-00600-w, ISSN: 1759-4782.
- Johnson DB, Balko JM. Primed for toxicity: CD4+ T cells and immune checkpoint inhibitors. Med (N Y). 2022 Mar 3/11/2022; 3(3): 155-6. PMID: 35590189, PII: S2666-6340(22)00086-1, DOI: 10.1016/j.medj.2022.02.003, ISSN: 2666-6340.
- Taylor BC, Balko JM. Mechanisms of MHC-I Downregulation and Role in Immunotherapy Response. Front Immunol. 2022; 13: 844866. PMID: 35296095, PMCID: PMC8920040, DOI: 10.3389/fimmu.2022.844866, ISSN: 1664-3224.
- Lehmann BD, Colaprico A, Silva TC, Chen J, An H, Ban Y, Huang H, Wang L, James JL, Balko JM, Gonzalez-Ericsson PI, Sanders ME, Zhang B, Pietenpol JA, Chen XS. Multi-omics analysis identifies therapeutic vulnerabilities in triple-negative breast cancer subtypes. Nat Commun. 2021 Nov 11/1/2021; 12(1): 6276. PMID: 34725325, PMCID: PMC8560912, PII: 10.1038/s41467-021-26502-6, DOI: 10.1038/s41467-021-26502-6, ISSN: 2041-1723.
- Hanna A, Balko JM. Breast cancer resistance mechanisms: challenges to immunotherapy. Breast Cancer Res Treat [print-electronic]. 2021 Nov; 190(1): 5-17. PMID: 34322780, PMCID: PMC8560575, PII: 10.1007/s10549-021-06337-x, DOI: 10.1007/s10549-021-06337-x, ISSN: 1573-7217.
- Jain NM, Schmalz L, Cann C, Holland A, Osterman T, Lang K, Wiesner GL, Pal T, Lovly C, Stricker T, Micheel C, Balko JM, Johnson DB, Park BH, Iams W. Framework for Implementing and Tracking a Molecular Tumor Board at a National Cancer Institute-Designated Comprehensive Cancer Center. Oncologist [print-electronic]. 2021 Nov; 26(11): e1962-e1970. PMID: 34390291, PMCID: PMC8571748, DOI: 10.1002/onco.13936, ISSN: 1549-490X.
- Chen X, Chen DG, Zhao Z, Balko JM, Chen J. Artificial image objects for classification of breast cancer biomarkers with transcriptome sequencing data and convolutional neural network algorithms. Breast Cancer Res. 2021 Oct 10/10/2021; 23(1): 96. PMID: 34629099, PMCID: PMC8504079, PII: 10.1186/s13058-021-01474-z, DOI: 10.1186/s13058-021-01474-z, ISSN: 1465-542X.
- Gonzalez-Ericsson PI, Wulfkhule JD, Gallagher RI, Sun X, Axelrod ML, Sheng Q, Luo N, Gomez H, Sanchez V, Sanders M, Pusztai L, Petricoin E, Blenman KRM, Balko JM, . Tumor-Specific Major Histocompatibility-II Expression Predicts Benefit to Anti-PD-1/L1 Therapy in Patients With HER2-Negative Primary Breast Cancer. Clin Cancer Res. 2021 Oct 10/1/2021; 27(19): 5299-306. PMID: 34315723, PMCID: PMC8792110, PII: 1078-0432.CCR-21-0607, DOI: 10.1158/1078-0432.CCR-21-0607, ISSN: 1557-3265.