For many malignancies, the molecular aberrations that occur predominantly in cancer cells have been elucidated. Considerable interest has been generated by the discovery of agents which specifically target these aberrations, and several of these compounds have entered into clinical evaluation and are showing great promise. Many of these novel targeted agents behave in ways that are fundamentally different from cytotoxic chemotherapy. For example, new agents may be cytostatic in nature, rather than cytotoxic, or may require long-term administration. These differences call for modifications in the design of clinical trials. Indeed, in contrast to the standard paradigm for Phase I development of classic chemotherapeutic agents based predominantly on determination of maximum tolerated dose (MTD), surrogate markers and functional endpoints may be fundamental parameters for development of targeted agents. We therefore hypothesize that integration of intermediate biologic endpoints which reflect interaction with or functional impact on the target, will provide critical information for determining the optimal biologic dose (OBD) for subsequent Phase II studies. Evaluation of the ability of targeted drugs to modulate, interact with, or inhibit specific molecular and biochemical targets requires effective cooperation between clinical and laboratory investigators. In a large institution such as The University of Texas M.D. Anderson Cancer Center, a strong emphasis on clinical and translational drug development exists. Investigators across the institution have access to all of the many components critical to this endeavor, including analytic chemistry, clinical pharmacology, functional imaging, biostatistics, and numerous basic research laboratories with state-of-the-art expertise in evaluating interactions of the test agents with specific cellular and molecular endpoints and effects on tumor cell growth and apoptosis. This extensive infrastructure for clinical and translational studies will allow us to safely and efficiently evaluate clinical activity and toxicity, pharmacokinetic parameters and pharmacodynamic relationships, and develop clinically-relevant correlates and surrogate endpoints for novel targeted agents given alone or in combination, hence permitting rapid advance of these compounds through early clinical studies. ? ?

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-SRRB-E (O1))
Program Officer
Wu, Roy S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas MD Anderson Cancer Center
Internal Medicine/Medicine
Other Domestic Higher Education
United States
Zip Code
Galanina, Natalie; Goodman, Aaron M; Cohen, Philip R et al. (2018) Successful Treatment of HIV-Associated Kaposi Sarcoma with Immune Checkpoint Blockade. Cancer Immunol Res 6:1129-1135
Goodman, Aaron M; Choi, Michael; Wieduwilt, Matthew et al. (2017) Next Generation Sequencing Reveals Potentially Actionable Alterations in the Majority of Patients with Lymphoid Malignancies. JCO Precis Oncol 1:
Gonzalez-Angulo, Ana M; Krop, Ian; Akcakanat, Argun et al. (2015) SU2C phase Ib study of paclitaxel and MK-2206 in advanced solid tumors and metastatic breast cancer. J Natl Cancer Inst 107:
Dasari, Arvind; Phan, Alexandria; Gupta, Sanjay et al. (2015) Phase I study of the anti-IGF1R antibody cixutumumab with everolimus and octreotide in advanced well-differentiated neuroendocrine tumors. Endocr Relat Cancer 22:431-41
Busaidy, Naifa L; LoRusso, Patricia; Lawhorn, Kristie et al. (2015) The Prevalence and Impact of Hyperglycemia and Hyperlipidemia in Patients With Advanced Cancer Receiving Combination Treatment With the Mammalian Target of Rapamycin Inhibitor Temsirolimus and Insulin Growth Factor-Receptor Antibody Cixutumumab. Oncologist 20:737-41
Ganesan, Prasanth; Moulder, Stacy; Lee, J Jack et al. (2014) Triple-negative breast cancer patients treated at MD Anderson Cancer Center in phase I trials: improved outcomes with combination chemotherapy and targeted agents. Mol Cancer Ther 13:3175-84
Hong, David S; Garrido-Laguna, Ignacio; Ekmekcioglu, Suhendan et al. (2014) Dual inhibition of the vascular endothelial growth factor pathway: a phase 1 trial evaluating bevacizumab and AZD2171 (cediranib) in patients with advanced solid tumors. Cancer 120:2164-73
Liu, Xiaochun; Lorusso, Patricia; Mita, Monica et al. (2014) Incidence of mucositis in patients treated with temsirolimus-based regimens and correlation to treatment response. Oncologist 19:426-8
Abrams, Jeffrey S; Mooney, Margaret M; Zwiebel, James A et al. (2013) Implementation of timeline reforms speeds initiation of National Cancer Institute-sponsored trials. J Natl Cancer Inst 105:954-9
Ganesan, Prasanth; Janku, Filip; Naing, Aung et al. (2013) Target-based therapeutic matching in early-phase clinical trials in patients with advanced colorectal cancer and PIK3CA mutations. Mol Cancer Ther 12:2857-63

Showing the most recent 10 out of 47 publications