Molecular Therapeutics Theme 1 Accomplishments

Identify and validate novel therapeutics, targets and pathways for selective tumor targeting and where possible advancing these into clinical trials. Research focus includes:

Scientific Accomplishments

Drs. Matherly and Polin have developed potent novel tumor-targeted cytotoxic agents based on the folate platform with selective membrane transport by the proton-coupled folate transporter (PCFT) and folate receptor (FR) α over the ubiquitously expressed reduced folate carrier. PCFT and FRα are highly expressed in tumors and provide means of selective tumor targeting. Studies in clinically relevant tumor cell models confirmed antitumor effects and in vivo efficacies were demonstrated with FRα- and PCFT- expressing human ovarian and mesothelioma xenografts in SCID mice. Plans are to progress these novel agents to clinical trials.

  • Lead researcher: Dr. Matherly
  • Collaborative researcher: Dr. Polin

Drs. Mohammad and Philip identified rationally designed nuclear transport inhibitors for treating pancreatic cancer. Their focus is on chromosome maintenance protein 1 (CRM1), a ubiquitous transport receptor that controls the nuclear export of key tumor suppressor and growth regulatory proteins. Over-expression of CRM1 is frequent in pancreatic cancer and is associated with increased histological grade, tumor size, metastasis and decreased survival. Based on promising preclinical results in pancreatic cancer cell lines and non-transformed human pancreatic ductal epithelial cells, patients are being enrolled on a phase I/IIb investigator-initiated clinical trial with the lead compound of this series.

  • Lead Researchers: Drs. Mohammad and Philip
  • Collaborative researchers: Drs. Heath, Mahaseth, Mohammad, Philip, Shields, Vaishampayan, and Harper

Investigation of ELK1 as a regulator of androgen receptor growth signaling receptors in prostate cancer. Researchers found that ELK1 directs a selective and sustained induction of genes that are critical for growth signaling by androgen receptor in prostate cancer cells. Studies are exploring whether disrupting the ELK1-androgen receptor interaction is possible and whether drugs can be developed for this purpose. With Dr. Heath, Dr. Ratnam is extending these studies to patients with the goal of an investigator-initiated clinical trial targeting the ELK1-AR interaction in prostate cancer patients.

  • Lead Researcher: Dr. Ratnam
  • Collaborative Researcher: Dr. Heath

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