Justin M. Balko, Pharm.D., Ph.D.

Assistant Professor

justin.balko@vanderbilt.edu
Faculty Appointments
Assistant Professor of Medicine Assistant Professor of Cancer BiologyAssistant Professor of Cancer Biology
Education
Ph.D., PHARMACEUTICAL SCIENCES, University of Kentucky, Lexington, KentuckyPharm.D., State University of New York, Buffalo, New York
Research Description
Our laboratory is focused on improving treatment oucomes in breast cancer (particularly triple-negative breast cancer) as well as in other solid tumors. To accomplish this, we integrate data from genomic and molecular profiling studies with molecular biology and signal transduction methodologies to translationally 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 (publically available databases), in vitro (cell culture), in vivo (mouse and human clinical studies) and in situ (histology) methods. We have a strong interest in the intersection between new immunotherapies and tumor cell signaling pathways.

We are currently exploring ways of targeting drug-resistant tumor cells which persist after neoadjuvant chemotherapy (NAC). NAC is used increasingly in patients with triple-negative breast cancer (TNBC), which does not express estrogen receptor, progesterone receptor or human epidermal growth factor-2 (HER2) amplification. The purpose of NAC is to increase the patient???s chances of undergoing breast-conserving surgery and to eliminate clinically silent micro-metastases. When employed, NAC results in pathological complete response (pCR) in about 30% of TNBC patients. These patients have a favorable recurrence-free and overall survival. The remaining patients with residual viable cancer in the breast or lymph nodes exhibit high rates of metastatic recurrence and an overall poor long term outcome.

Importantly, there are no approved therapies for use in TNBC patients with residual disease at surgery following NAC. For these patients, the standard of care is watchful waiting. In light of this, we performed molecular profiling of the residual disease from such patients in order to identify clinically actionable alterations that could be exploited therapeutically to reduce recurrence and mortality. From these studies, we have identified loss of dual specificity phosphatase 4 (DUSP4) in a significant percentage of post-NAC TNBCs (Balko et al, Nature Medicine, 2012) . DUSP4 is a phosphatase which negatively regulates the MEK and JNK signaling pathways and is a potential tumor suppressor. We have recently shown that DUSP4 regulates cancer stem cell-like phenotypes and chemotherapeutic resistance (Balko et al, Cancer Research, 2013). Furthermore, our mechanistic studies suggest that DUSP4-deficient breast tumor models are targetable by inhibitors of MEK or ERK.

We have also recently used targeted next-generation sequencing to characterize the spectrum of tumor-genome lesions in a series of 74 post-NAC TNBCs and have detected several potentially actionable molecular alterations (Balko et al, Cancer Discovery, 2014). Importantly, several of these alterations (including amplification of MCL1, JAK2, and loss of PTEN) are enriched in residual drug-resistant tumors after chemotherapy compared to primary untreated tumors. These data suggest additional actionable molecular targets which could be exploited in the adjuvant setting to reduce recurrence and improve survival of this devastating disease, and validation of these concepts will also be a continuing focus of the laboratory.
Research Keywords
Translational cancer research with focuses on molecular therapeutics, onco-immunology and bioinformatics
Publications
Amato KR, Wang S, Tan L, Hastings AK, Song W, Lovly CM, Meador CB, Ye F, Lu P, Balko JM, Colvin DC, Cates JM, Pao W, Gray NS, Chen J. EPHA2 Blockade Overcomes Acquired Resistance to EGFR Kinase Inhibitors in Lung Cancer. Cancer Res [print-electronic]. 2016 Jan 1/15/2016; 76(2): 305-18. PMID: 26744526, PMCID: PMC4715957, PII: 0008-5472.CAN-15-0717, DOI: 10.1158/0008-5472.CAN-15-0717, ISSN: 1538-7445.

Loi S, Dushyanthen S, Beavis PA, Salgado R, Denkert C, Savas P, Combs S, Rimm DL, Giltnane JM, Estrada MV, Sánchez V, Sanders ME, Cook RS, Pilkinton MA, Mallal SA, Wang K, Miller VA, Stephens PJ, Yelensky R, Doimi FD, Gómez H, Ryzhov SV, Darcy PK, Arteaga CL, Balko JM. RAS/MAPK Activation Is Associated with Reduced Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors. Clin. Cancer Res [print-electronic]. 2015 Oct 10/29/2015; PMID: 26515496, PII: 1078-0432.CCR-15-1125, DOI: 10.1158/1078-0432.CCR-15-1125, ISSN: 1078-0432.

Dillon LM, Bean JR, Yang W, Shee K, Symonds LK, Balko JM, McDonald WH, Liu S, Gonzalez-Angulo AM, Mills GB, Arteaga CL, Miller TW. P-REX1 creates a positive feedback loop to activate growth factor receptor, PI3K/AKT and MEK/ERK signaling in breast cancer. Oncogene [print-electronic]. 2015 Jul 7/23/2015; 34(30): 3968-76. PMID: 25284585, PMCID: PMC4387124, PII: onc2014328, DOI: 10.1038/onc.2014.328, ISSN: 1476-5594.

Bhola NE, Jansen VM, Bafna S, Giltnane JM, Balko JM, Estrada MV, Meszoely I, Mayer I, Abramson V, Ye F, Sanders M, Dugger TC, Allen EV, Arteaga CL. Kinome-wide functional screen identifies role of PLK1 in hormone-independent, ER-positive breast cancer. Cancer Res [print-electronic]. 2015 Jan 1/15/2015; 75(2): 405-14. PMID: 25480943, PMCID: PMC4297507, PII: 0008-5472.CAN-14-2475, DOI: 10.1158/0008-5472.CAN-14-2475, ISSN: 1538-7445.

Castaneda CA, Lopez-Ilasaca M, Pinto JA, Chirinos-Arias M, Doimi F, Neciosup SP, Rojas KI, Vidaurre T, Balko JM, Arteaga CL, Gomez HL. PIK3CA mutations in Peruvian patients with HER2-amplified and triple negative non-metastatic breast cancers. Hematol Oncol Stem Cell Ther [print-electronic]. 2014 Dec; 7(4): 142-8. PMID: 25467032, PII: S1658-3876(14)00084-3, DOI: 10.1016/j.hemonc.2014.09.007, ISSN: 1658-3876.

Baglia ML, Cai Q, Zheng Y, Wu J, Su Y, Ye F, Bao PP, Cai H, Zhao Z, Balko J, Zheng W, Lu W, Shu XO. Dual specificity phosphatase 4 gene expression in association with triple-negative breast cancer outcome. Breast Cancer Res. Treat [print-electronic]. 2014 Nov; 148(1): 211-20. PMID: 25281216, PMCID: PMC4200532, DOI: 10.1007/s10549-014-3127-z, ISSN: 1573-7217.

Johnson DB, Dahlman KH, Knol J, Gilbert J, Puzanov I, Means-Powell J, Balko JM, Lovly CM, Murphy BA, Goff LW, Abramson VG, Crispens MA, Mayer IA, Berlin JD, Horn L, Keedy VL, Reddy NM, Arteaga CL, Sosman JA, Pao W. Enabling a genetically informed approach to cancer medicine: a retrospective evaluation of the impact of comprehensive tumor profiling using a targeted next-generation sequencing panel. Oncologist [print-electronic]. 2014 Jun; 19(6): 616-22. PMID: 24797823, PMCID: PMC4041676, PII: theoncologist.2014-0011, DOI: 10.1634/theoncologist.2014-0011, ISSN: 1549-490X.

Giltnane JM, Balko JM. Rationale for targeting the Ras/MAPK pathway in triple-negative breast cancer. Discov Med. 2014 May; 17(95): 275-83. PMID: 24882719, ISSN: 1944-7930.

Mayer IA, Abramson VG, Isakoff SJ, Forero A, Balko JM, Kuba MG, Sanders ME, Yap JT, Van den Abbeele AD, Li Y, Cantley LC, Winer E, Arteaga CL. Stand up to cancer phase Ib study of pan-phosphoinositide-3-kinase inhibitor buparlisib with letrozole in estrogen receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. J. Clin. Oncol [print-electronic]. 2014 Apr 4/20/2014; 32(12): 1202-9. PMID: 24663045, PMCID: PMC3986383, PII: JCO.2013.54.0518, DOI: 10.1200/JCO.2013.54.0518, ISSN: 1527-7755.

Jeselsohn R, Yelensky R, Buchwalter G, Frampton G, Meric-Bernstam F, Gonzalez-Angulo AM, Ferrer-Lozano J, Perez-Fidalgo JA, Cristofanilli M, Gómez H, Arteaga CL, Giltnane J, Balko JM, Cronin MT, Jarosz M, Sun J, Hawryluk M, Lipson D, Otto G, Ross JS, Dvir A, Soussan-Gutman L, Wolf I, Rubinek T, Gilmore L, Schnitt S, Come SE, Pusztai L, Stephens P, Brown M, Miller VA. Emergence of constitutively active estrogen receptor-a mutations in pretreated advanced estrogen receptor-positive breast cancer. Clin. Cancer Res [print-electronic]. 2014 Apr 4/1/2014; 20(7): 1757-67. PMID: 24398047, PMCID: PMC3998833, PII: 1078-0432.CCR-13-2332, DOI: 10.1158/1078-0432.CCR-13-2332, ISSN: 1078-0432.

Balko JM, Giltnane JM, Wang K, Schwarz LJ, Young CD, Cook RS, Owens P, Sanders ME, Kuba MG, Sánchez V, Kurupi R, Moore PD, Pinto JA, Doimi FD, Gómez H, Horiuchi D, Goga A, Lehmann BD, Bauer JA, Pietenpol JA, Ross JS, Palmer GA, Yelensky R, Cronin M, Miller VA, Stephens PJ, Arteaga CL. Molecular profiling of the residual disease of triple-negative breast cancers after neoadjuvant chemotherapy identifies actionable therapeutic targets. Cancer Discov [print-electronic]. 2014 Feb; 4(2): 232-45. PMID: 24356096, PMCID: PMC3946308, PII: 2159-8290.CD-13-0286, DOI: 10.1158/2159-8290.CD-13-0286, ISSN: 2159-8290.

Balko JM, Schwarz LJ, Bhola NE, Kurupi R, Owens P, Miller TW, Gómez H, Cook RS, Arteaga CL. Activation of MAPK pathways due to DUSP4 loss promotes cancer stem cell-like phenotypes in basal-like breast cancer. Cancer Res [print-electronic]. 2013 Oct 10/15/2013; 73(20): 6346-58. PMID: 23966295, PMCID: PMC4090144, PII: 0008-5472.CAN-13-1385, DOI: 10.1158/0008-5472.CAN-13-1385, ISSN: 1538-7445.

Morrison MM, Hutchinson K, Williams MM, Stanford JC, Balko JM, Young C, Kuba MG, Sánchez V, Williams AJ, Hicks DJ, Arteaga CL, Prat A, Perou CM, Earp HS, Massarweh S, Cook RS. ErbB3 downregulation enhances luminal breast tumor response to antiestrogens. J. Clin. Invest [print-electronic]. 2013 Oct; 123(10): 4329-43. PMID: 23999432, PMCID: PMC3784526, PII: 66764, DOI: 10.1172/JCI66764, ISSN: 1558-8238.

Hanker AB, Pfefferle AD, Balko JM, Kuba MG, Young CD, Sánchez V, Sutton CR, Cheng H, Perou CM, Zhao JJ, Cook RS, Arteaga CL. Mutant PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2013 Aug 8/27/2013; 110(35): 14372-7. PMID: 23940356, PMCID: PMC3761610, PII: 1303204110, DOI: 10.1073/pnas.1303204110, ISSN: 1091-6490.

Young CD, Pfefferle AD, Owens P, Kuba MG, Rexer BN, Balko JM, Sánchez V, Cheng H, Perou CM, Zhao JJ, Cook RS, Arteaga CL. Conditional loss of ErbB3 delays mammary gland hyperplasia induced by mutant PIK3CA without affecting mammary tumor latency, gene expression, or signaling. Cancer Res [print-electronic]. 2013 Jul 7/1/2013; 73(13): 4075-85. PMID: 23633485, PMCID: PMC3702683, PII: 0008-5472.CAN-12-4579, DOI: 10.1158/0008-5472.CAN-12-4579, ISSN: 1538-7445.

Dennison JB, Molina JR, Mitra S, González-Angulo AM, Balko JM, Kuba MG, Sanders ME, Pinto JA, Gómez HL, Arteaga CL, Brown RE, Mills GB. Lactate dehydrogenase B: a metabolic marker of response to neoadjuvant chemotherapy in breast cancer. Clin. Cancer Res [print-electronic]. 2013 Jul 7/1/2013; 19(13): 3703-13. PMID: 23697991, PMCID: PMC3727144, PII: 1078-0432.CCR-13-0623, DOI: 10.1158/1078-0432.CCR-13-0623, ISSN: 1078-0432.

Bhola NE, Balko JM, Dugger TC, Kuba MG, Sánchez V, Sanders M, Stanford J, Cook RS, Arteaga CL. TGF-ß inhibition enhances chemotherapy action against triple-negative breast cancer. J. Clin. Invest [print-electronic]. 2013 Mar; 123(3): 1348-58. PMID: 23391723, PMCID: PMC3582135, PII: 65416, DOI: 10.1172/JCI65416, ISSN: 1558-8238.

Balko JM, Stricker TP, Arteaga CL. The genomic map of breast cancer: which roads lead to better targeted therapies?. Breast Cancer Res. 2013; 15(4): 209. PMID: 23905624, PMCID: PMC3979080, PII: bcr3435, DOI: 10.1186/bcr3435, ISSN: 1465-542X.

Balko JM, Mayer IA, Sanders ME, Miller TW, Kuba MG, Meszoely IM, Wagle N, Garraway LA, Arteaga CL. Discordant cellular response to presurgical letrozole in bilateral synchronous ER+ breast cancers with a KRAS mutation or FGFR1 gene amplification. Mol. Cancer Ther [print-electronic]. 2012 Oct; 11(10): 2301-5. PMID: 22879364, PMCID: PMC3682668, PII: 1535-7163.MCT-12-0511, DOI: 10.1158/1535-7163.MCT-12-0511, ISSN: 1538-8514.

Balko JM, Cook RS, Vaught DB, Kuba MG, Miller TW, Bhola NE, Sanders ME, Granja-Ingram NM, Smith JJ, Meszoely IM, Salter J, Dowsett M, Stemke-Hale K, González-Angulo AM, Mills GB, Pinto JA, Gómez HL, Arteaga CL. Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance. Nat. Med. 2012 Jul; 18(7): 1052-9. PMID: 22683778, PMCID: PMC3693569, PII: nm.2795, DOI: 10.1038/nm.2795, ISSN: 1546-170X.

Balko JM, Arteaga CL. Molecular signatures of lung cancer: defining new diagnostic and therapeutic paradigms. Mol Diagn Ther. 2012 Feb 2/1/2012; 16(1): 1-6. PMID: 22339590, DOI: 10.2165/11597430-000000000-00000, ISSN: 1179-2000.

Balko JM, Miller TW, Morrison MM, Hutchinson K, Young C, Rinehart C, Sánchez V, Jee D, Polyak K, Prat A, Perou CM, Arteaga CL, Cook RS. The receptor tyrosine kinase ErbB3 maintains the balance between luminal and basal breast epithelium. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2012 Jan 1/3/2012; 109(1): 221-6. PMID: 22178756, PMCID: PMC3252958, PII: 1115802109, DOI: 10.1073/pnas.1115802109, ISSN: 1091-6490.

Bryant JL, Britson J, Balko JM, Willian M, Timmons R, Frolov A, Black EP. A microRNA gene expression signature predicts response to erlotinib in epithelial cancer cell lines and targets EMT. Br. J. Cancer [print-electronic]. 2012 Jan 1/3/2012; 106(1): 148-56. PMID: 22045191, PMCID: PMC3251842, PII: bjc2011465, DOI: 10.1038/bjc.2011.465, ISSN: 1532-1827.

Oh YT, Yue P, Zhou W, Balko JM, Black EP, Owonikoko TK, Khuri FR, Sun SY. Oncogenic Ras and B-Raf proteins positively regulate death receptor 5 expression through co-activation of ERK and JNK signaling. J. Biol. Chem [print-electronic]. 2012 Jan 1/2/2012; 287(1): 257-67. PMID: 22065586, PMCID: PMC3249076, PII: M111.304006, DOI: 10.1074/jbc.M111.304006, ISSN: 1083-351X.

Miller TW, Balko JM, Arteaga CL. Phosphatidylinositol 3-kinase and antiestrogen resistance in breast cancer. J. Clin. Oncol [print-electronic]. 2011 Nov 11/20/2011; 29(33): 4452-61. PMID: 22010023, PMCID: PMC3221526, PII: JCO.2010.34.4879, DOI: 10.1200/JCO.2010.34.4879, ISSN: 1527-7755.

Fox EM, Miller TW, Balko JM, Kuba MG, Sánchez V, Smith RA, Liu S, González-Angulo AM, Mills GB, Ye F, Shyr Y, Manning HC, Buck E, Arteaga CL. A kinome-wide screen identifies the insulin/IGF-I receptor pathway as a mechanism of escape from hormone dependence in breast cancer. Cancer Res [print-electronic]. 2011 Nov 11/1/2011; 71(21): 6773-84. PMID: 21908557, PMCID: PMC3206206, PII: 0008-5472.CAN-11-1295, DOI: 10.1158/0008-5472.CAN-11-1295, ISSN: 1538-7445.

Miller TW, Balko JM, Fox EM, Ghazoui Z, Dunbier A, Anderson H, Dowsett M, Jiang A, Smith RA, Maira SM, Manning HC, González-Angulo AM, Mills GB, Higham C, Chanthaphaychith S, Kuba MG, Miller WR, Shyr Y, Arteaga CL. ERa-dependent E2F transcription can mediate resistance to estrogen deprivation in human breast cancer. Cancer Discov [print-electronic]. 2011 Sep; 1(4): 338-51. PMID: 22049316, PMCID: PMC3204388, PII: 2159-8290.CD-11-0101, DOI: 10.1158/2159-8290.CD-11-0101, ISSN: 2159-8290.

Balko JM, Arteaga CL. Dead-box or black-box: is DDX1 a potential biomarker in breast cancer?. Breast Cancer Res. Treat [print-electronic]. 2011 May; 127(1): 65-7. PMID: 20694745, DOI: 10.1007/s10549-010-1105-7, ISSN: 1573-7217.

Miller TW, Balko JM, Ghazoui Z, Dunbier A, Anderson H, Dowsett M, González-Angulo AM, Mills GB, Miller WR, Wu H, Shyr Y, Arteaga CL. A gene expression signature from human breast cancer cells with acquired hormone independence identifies MYC as a mediator of antiestrogen resistance. Clin. Cancer Res [print-electronic]. 2011 Apr 4/1/2011; 17(7): 2024-34. PMID: 21346144, PMCID: PMC3221728, PII: 1078-0432.CCR-10-2567, DOI: 10.1158/1078-0432.CCR-10-2567, ISSN: 1078-0432.

Ghosh R, Narasanna A, Wang SE, Liu S, Chakrabarty A, Balko JM, González-Angulo AM, Mills GB, Penuel E, Winslow J, Sperinde J, Dua R, Pidaparthi S, Mukherjee A, Leitzel K, Kostler WJ, Lipton A, Bates M, Arteaga CL. Trastuzumab has preferential activity against breast cancers driven by HER2 homodimers. Cancer Res [print-electronic]. 2011 Mar 3/1/2011; 71(5): 1871-82. PMID: 21324925, PMCID: PMC3221734, PII: 0008-5472.CAN-10-1872, DOI: 10.1158/0008-5472.CAN-10-1872, ISSN: 1538-7445.

Balko JM, Black EP. Do the genes tell us the path of most resistance?. Cancer Biol. Ther. 2011 Jan 1/15/2011; 11(2): 213-5. PMID: 21263213, PII: 13922, DOI: 10.4161/cbt.11.2.13922, ISSN: 1555-8576.

Available Postdoctoral Position Details
Posted: 4/28/2015
We are seeking a postdoctoral fellows to conduct multidisciplinary translational research on the cutting edge intersection of cancer biology, bioinformatics, and clinical research. All positions are currently filled, but we can always accept applications or CVs from outstanding candidates.

The ideal applicant will have a strong translational background, with skills or proficiency in molecular biology, mouse models of cancer, and/or bioinformatic analysis of genomic data. Fellows with skills in any or all of the areas are encouraged to contact the PI.
The fellow will have the opportunity to conduct in vitro, in vivo, and ex vivo studies along these lines with a clear potential for patient impact, in a well-funded, publication-forward laboratory setting.

The fellow will be expected to work independently, but will have the support of the cancer center resources including a strong multidisciplinary and collaborative environment.