Profile

My research focus is on new therapeutic strategies focusing on the phosphatidylinositol-3 kinase (PI3K)/Akt and correlated pathways in triple-negative, hormone-refractory and HER2-overexpressing refractory breast cancers, using biologically-based targeted agents. I plan to perform molecular analysis of individual breast cancers in an attempt to determine how the biology of the cancer affects the response to the therapeutic agent. It is also my goal to play a key role in elucidating mechanisms of therapy resistance for patients with triple-negative, resistant ER-positive and resistant HER2-positive breast cancers. Ultimately this will result in better and more rational patient/therapy selection.

My role as a clinical investigator are as follows:
1) Develop a Clinical Breast Cancer Research Program with strong links to laboratory efforts throughout the medical center and if necessary, external to the institution. This goal involves collaboration with prestigious investigators within and outside Vanderbilt, and consists of a bidirectional process: observations made in the clinic and correlative studies in tissue samples from clinical trial patients with breast cancer lead basic scientists to investigate new areas of research. Conversely, pre-clinical data focused on relevant signaling pathways in breast cancer are the basis for development and implementation of novel hypothesis-driven clinical trials.
2) Expand preclinical therapeutic testing with tumors freshly obtained from the breast cancer patients in clinical trials. Tissue collection (primary tumor paraffin blocks and/or fresh frozen tissue) in all investigator-initiated breast cancer clinical trials is required for patient enrollment. Thanks to our Multidisciplinary Breast Cancer Clinic, we have been extremely successful in enrolling patients to clinical trials requiring research biopsies.
3) Develop and perform hypothesis-driven, translational clinical trials with biologically-based targeted therapeutics that are based on preclinical findings obtained in vitro and/or in vivo in human and murine systems, to address the most important issues in breast cancer .

My research endeavors are focused on the role of the following correlated key cell signaling pathways in breast cancer: PI3K/Akt, erbB (EGFR, HER2/neu), and Insulin-like Growth Factor (IGF)-1 pathways. I have developed targeted-oriented clinical trials addressing the role of these pathways in the development of resistance to antiestrogens and trastuzumab, as well as their role in triple-negative, basal-like tumors. This strategy will provide better understanding of breast cancer biology and of the molecular determinants of clinical efficacy, by optimally characterizing the molecular features of the breast cancer to be treated. This will foster target-assay development in a more limited number of patients. In turn, these results will be instrumental in expediting subsequent development of molecularly targeted agents, providing a platform for prioritization of novel combinations and elucidation of preferential mechanisms of escape from these therapies.

Examples of some of my investigator-initiated clinical trials include:

VICCBRE0949: A phase I/II study of cisplatin, paclitaxel and RAD001 in patients with metastatic breast cancer

VICCBRE0904: A phase II neoadjuvant study of cisplatin, paclitaxel with or without RAD001 in patients with triple-negative locally advanced breast cancer

VICCBRE09112: A phase II trial of endocrine therapy in combination with OSI-906 (an IGF-1R inhibitor) and erlotinib (Tarcevaâ„¢, an EGFR inhibitor) in patients with hormone-sensitive metastatic breast cancer

VICCBRE0942: A pre-surgical trial of metformin in patients with operable early breast cancer

VICCBRE0983: A Prospective Clinical Trial evaluating Potential Biomarkers for Bevacizumab Induced Hypertension

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

1. New strategies for triple-negative breast cancer--deciphering the heterogeneity. Mayer IA, Abramson VG, Lehmann BD, Pietenpol JA (2014) Clin Cancer Res 20(4): 782-90
   › Primary publication · 24536073 (PubMed) · PMC3962777 (PubMed Central)
2. Gefitinib and celecoxib in advanced metastatic gastrointestinal tumors: a pilot feasibility study. Yamaguchi NH, Mayer IA, Malzyner A, de Andrade CJ, Murad AM, Del Giglio A, Alves V (2014) J Gastrointest Oncol 5(1): 57-66
   › Primary publication · 24490043 (PubMed) · PMC3904021 (PubMed Central)
3. DCE-MRI analysis methods for predicting the response of breast cancer to neoadjuvant chemotherapy: pilot study findings. Li X, Arlinghaus LR, Ayers GD, Chakravarthy AB, Abramson RG, Abramson VG, Atuegwu N, Farley J, Mayer IA, Kelley MC, Meszoely IM, Means-Powell J, Grau AM, Sanders M, Bhave SR, Yankeelov TE (2014) Magn Reson Med 71(4): 1592-602
   › Primary publication · 23661583 (PubMed) · PMC3742614 (PubMed Central)
4. Metastatic breast cancer, version 1.2012: featured updates to the NCCN guidelines. Carlson RW, Allred DC, Anderson BO, Burstein HJ, Edge SB, Farrar WB, Forero A, Giordano SH, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis CA, Isakoff SJ, Ljung BM, Mankoff DA, Marcom PK, Mayer IA, McCormick B, Pierce LJ, Reed EC, Smith ML, Soliman H, Somlo G, Theriault RL, Ward JH, Wolff AC, Zellars R, Kumar R, Shead DA, National Comprehensive Cancer Network (2012) J Natl Compr Canc Netw 10(7): 821-9
   › Primary publication · 22773798 (PubMed) · PMC3753191 (PubMed Central)
5. Improving survival and limiting toxicity: latest advances in treating human epidermal growth factor receptor 2 overexpressing breast cancer. Abramson VG, Mayer IA (2012) Ther Adv Med Oncol 4(3): 139-47
   › Primary publication · 22590487 (PubMed) · PMC3349077 (PubMed Central)
6. Invasive breast cancer. Carlson RW, Allred DC, Anderson BO, Burstein HJ, Carter WB, Edge SB, Erban JK, Farrar WB, Forero A, Giordano SH, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis CA, Ljung BM, Mankoff DA, Marcom PK, Mayer IA, McCormick B, Pierce LJ, Reed EC, Sachdev J, Smith ML, Somlo G, Ward JH, Wolff AC, Zellars R, National Comprehensive Cancer Network (2011) J Natl Compr Canc Netw 9(2): 136-222
   › Primary publication · 21310842 (PubMed)
7. Evaluation of metformin in early breast cancer: a modification of the traditional paradigm for clinical testing of anti-cancer agents. Goodwin PJ, Stambolic V, Lemieux J, Chen BE, Parulekar WR, Gelmon KA, Hershman DL, Hobday TJ, Ligibel JA, Mayer IA, Pritchard KI, Whelan TJ, Rastogi P, Shepherd LE (2011) Breast Cancer Res Treat 126(1): 215-20
   › Primary publication · 20976543 (PubMed)
8. Breast cancer: noninvasive and special situations. Carlson RW, Allred DC, Anderson BO, Burstein HJ, Carter WB, Edge SB, Erban JK, Farrar WB, Forero A, Giordano SH, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis CA, Ljung BM, Marcom PK, Mayer IA, McCormick B, Pierce LJ, Reed EC, Smith ML, Somlo G, Topham NS, Ward JH, Winer EP, Wolff AC (2010) J Natl Compr Canc Netw 8(10): 1182-207
   › Primary publication · 20971842 (PubMed)
9. Antiangiogenic therapies in early-stage breast cancer. Derleth C, Mayer IA (2010) Clin Breast Cancer : E23-31
   › Primary publication · 20587404 (PubMed) · PMC3471531 (PubMed Central)
10. The Rac1/p38 mitogen-activated protein kinase pathway is required for interferon alpha-dependent transcriptional activation but not serine phosphorylation of Stat proteins. Uddin S, Lekmine F, Sharma N, Majchrzak B, Mayer I, Young PR, Bokoch GM, Fish EN, Platanias LC (2000) J Biol Chem 275(36): 27634-40
    › Primary publication · 10878008 (PubMed)

Keywords & MeSH Terms

MeSH terms are retrieved from PubMed records. Learn more.

Key: MeSH Term Keyword

Algorithms Breast Cancer Clinical Trials as Topic Computer Simulation Contrast Media Diffusion Magnetic Resonance Imaging Enzyme Activation Follow-Up Studies Gene Expression Regulation, Neoplastic Genomics Homeodomain Proteins Humans Interferon-alpha Kaplan-Meier Estimate Letrozole MAP Kinase Signaling System Milk Proteins Mutation Neoplasm Recurrence, Local Neuregulins Nuclear Proteins Postmenopause Protein-Serine-Threonine Kinases Pyridines Randomized Controlled Trials as Topic STAT3 Transcription Factor STAT5 Transcription Factor Tamoxifen Transcriptional Activation Tyrosine Up-Regulation