INNOVATIVE TUMOR TARGETED THERAPIES FOR LUNG CANCER

Summary

Principal Investigator: R Perez-Soler
Abstract: The objective of this application is to develop innovative tumor- targeted therapies for lung cancer and bronchial premalignancy. The general hypothesis is that therapeutic strategies that combine anatomical and molecular targeting should constitute improved therapeutic modalities for these conditions. Three major therapeutic strategies will be pursued: 1) inhaled therapeutics for bronchial premalignancy, 2) inhibition of pathways that play a major role in lung cancer dysregulated growth, and 3) anatomical targeting. Three prototype projects within these three major strategies are proposed: 1) preclinical and initial clinical evaluation of an aerosolized liposome/p53 formulation in patients with lung cancer and bronchial premalignancy carrying p53 mutations, 2) clinical studies of synergism between chemotherapy and the anti-EGFR monoclonal antibody C225 in stage IIIA NSCLC, and 3) integration of intrapleural therapy in the treatment of patients with stage IIB NSCLC with malignant pleural effusion. All three projects include the performance of clinical trials that incorporate the measurement of pharmacological or molecular parameters potentially correlated with the observed antitumor effect. The work proposed is a logical continuation of the applicant's translational research efforts in the areas of drug delivery and lung cancer therapy research during the last decade. The specific projects will be conducted by young clinical investigators mentored by the applicant. Candidates for mentorship under this proposal will include fellows enrolled in the Medical Oncology fellowship at NYU and junior staff members of the Divisions of Hematology, Pulmonary Medicine, and Surgery. Four such candidates have already been identified. It is anticipated that a total of ten young clinical investigators will be mentored during a five-year period.
Funding Period: 2000-09-01 - 2006-08-31
more information: NIH RePORT

Top Publications

  1. ncbi PM02734 (elisidepsin) induces caspase-independent cell death associated with features of autophagy, inhibition of the Akt/mTOR signaling pathway, and activation of death-associated protein kinase
    Yi He Ling
    Division of Medical Oncology, Department of Surgery, Albert Einstein College of Medicine, Bronx, New York, USA
    Clin Cancer Res 17:5353-66. 2011
  2. ncbi Enhanced sensitivity to the HER1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib hydrochloride in chemotherapy-resistant tumor cell lines
    Qun Dai
    Department of Oncology, Montefiore Medical Center Albert Einstein College of Medicine, 11 East 210th Street, Bronx, NY 10467, USA
    Clin Cancer Res 11:1572-8. 2005
  3. ncbi Schedule-dependent cytotoxic synergism of pemetrexed and erlotinib in human non-small cell lung cancer cells
    Tianhong Li
    Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Clin Cancer Res 13:3413-22. 2007
  4. ncbi Erlotinib induces mitochondrial-mediated apoptosis in human H3255 non-small-cell lung cancer cells with epidermal growth factor receptorL858R mutation through mitochondrial oxidative phosphorylation-dependent activation of BAX and BAK
    Yi He Ling
    Division of Medical Oncology, Albert Einstein College of Medicine, Bronx, New York, USA
    Mol Pharmacol 74:793-806. 2008
  5. pmc Molecular pharmacodynamics of PM02734 (elisidepsin) as single agent and in combination with erlotinib; synergistic activity in human non-small cell lung cancer cell lines and xenograft models
    Yi He Ling
    Division of Medical Oncology, Albert Einstein College of Medicine, Bronx, New York, USA
    Eur J Cancer 45:1855-64. 2009

Scientific Experts

  • Tianhong Li
  • Yi He Ling
  • Roman Perez-Soler
  • Yiyu Zou
  • Miguel Aracil
  • Jose Jimeno
  • Qun Dai
  • Bo Lu
  • Ana Maria Cuervo
  • Ziqiang Yuan
  • Ruoping Lin
  • Marie Lia
  • Kenneth K Iwata
  • Glenn Kroog
  • Yi Yu Zou

Detail Information

Publications5

  1. ncbi PM02734 (elisidepsin) induces caspase-independent cell death associated with features of autophagy, inhibition of the Akt/mTOR signaling pathway, and activation of death-associated protein kinase
    Yi He Ling
    Division of Medical Oncology, Department of Surgery, Albert Einstein College of Medicine, Bronx, New York, USA
    Clin Cancer Res 17:5353-66. 2011
    ..PM02734 (elisidepsin) is a synthetic marine-derived cyclic peptide of the kahalalide family currently in phase II clinical development. The mechanisms of cell death induced by PM02734 remain unknown...
  2. ncbi Enhanced sensitivity to the HER1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib hydrochloride in chemotherapy-resistant tumor cell lines
    Qun Dai
    Department of Oncology, Montefiore Medical Center Albert Einstein College of Medicine, 11 East 210th Street, Bronx, NY 10467, USA
    Clin Cancer Res 11:1572-8. 2005
    ..We hypothesized that some tumors treated with multiple cytotoxic therapies may become more dependent on the HER1/EGFR signaling pathways for survival...
  3. ncbi Schedule-dependent cytotoxic synergism of pemetrexed and erlotinib in human non-small cell lung cancer cells
    Tianhong Li
    Department of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Clin Cancer Res 13:3413-22. 2007
    ..This study was undertaken to select the optimal combination schedule of erlotinib and pemetrexed for the treatment of relapsed non-small cell lung cancer (NSCLC) using a panel of human NSCLC lines...
  4. ncbi Erlotinib induces mitochondrial-mediated apoptosis in human H3255 non-small-cell lung cancer cells with epidermal growth factor receptorL858R mutation through mitochondrial oxidative phosphorylation-dependent activation of BAX and BAK
    Yi He Ling
    Division of Medical Oncology, Albert Einstein College of Medicine, Bronx, New York, USA
    Mol Pharmacol 74:793-806. 2008
    ..Our data indicate that activation of BAX and BAK plays a critical role in the initiation of erlotinib-induced apoptotic cascades...
  5. pmc Molecular pharmacodynamics of PM02734 (elisidepsin) as single agent and in combination with erlotinib; synergistic activity in human non-small cell lung cancer cell lines and xenograft models
    Yi He Ling
    Division of Medical Oncology, Albert Einstein College of Medicine, Bronx, New York, USA
    Eur J Cancer 45:1855-64. 2009
    ..These results have provided a rational basis for an ongoing clinical trial to explore this combination in patients with advanced malignant solid tumours...