Research in Dr. Hernandez’s lab, the Metastasis Biology Section, seeks to interrogate the molecular underpinnings of metastatic colonization, which cause greater than 90% of cancer related deaths. The ability to recapitulate the complexities of human tumor metastases has been, and remains, a major obstacle in the progress of cancer care. To address this need, the lab has pioneered systems to sustain intact tumor and surrounding normal tissue from the operating room outside the patient (ex vivo). We hypothesize that implementation of our systems will carry broad implications across many fields of medicine and potentially fundamentally alter the translational research landscape. Moreover, given that our systems are based on an individual patient’s metastases, the benefits of personalized medicine could leap from generating lists of potentially useful drugs to designation of efficacious agents/trials for that patient. At present, the Hernandez Lab is employing our human metastatic cancer systems to:

1. Identify and target mechanisms that support the survival and outgrowth of latent, disseminated tumor cells in the liver.
2. Characterize a novel oncogenic signaling axis involving mis-localization of a nuclear export protein, XPO7.

3. Advance hepatic regional therapy through

   • The addition of new perfusion agents to standard-of-care floxuridine
   • Mitigation of floxuridine-mediated biliary toxicity
   • The use of an antibody-drug conjugate (IL-12) to abrogate immunosuppressive tumor microenvironments
4. Characterize tumor microenvironment dynamics (with and without immuno-oncology drugs) with the employment of our live imaging platform.
5. Decipher the cellular roles of therapeutically targetable protein kinases (identified through substrate sequence specificity) for cancers lacking targetable driver mutations.