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:
- 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) - 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) - 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) - 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) - 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) - 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) - 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) - 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) - Antiangiogenic therapies in early-stage breast cancer. Derleth C, Mayer IA (2010) Clin Breast Cancer : E23-31
› Primary publication · 20587404 (PubMed) · PMC3471531 (PubMed Central) - 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)