b'Catalysts of ProgressCatalysts of ProgressPatients play a vital role in driving kidney cancer research forward. Tao Wang, Ph.D., employs state-of-the-art quantitative approachesincluding bioinformatics and biostatisticsto study kidney cancer heterogeneity, metastasis, prognosis, and treatment response.Innovative Biobanking Neither the genomics nor the biobank or the avatar program would have been Patients at UT Southwestern have sup- on studies of cancer samples donatedanalyses and an avatar program.possible without the strong support from our patients and the gift of their tumor ported seminal discoveries by donatingby patients.UT Southwestern has pioneered thesamples for research. tumor samples collected during surgery.The biobank is part of the Biospecimenlargest program for the preservation ofJames Brugarolas, M.D., Ph.D.,For example, discoveries related to genesand Pathology Core, a crucial componentlive tumor samples. Tumor samples areDirector, Kidney Cancer Programimplicated in kidney cancer have set theof the SPORE (see page 13). The biobankfrozen in a way that maintains live cells. foundation of a modern cancer classifica- collects samples donated by patientsWith more than 1,500 kidney cancers tion (see page 40). These were all basedundergoing surgery to support genomicpreserved live, the collection may be thelargest in the world. Preserving cancerpattern, and appearance of the parent cells live allows scientists to examinetumor. In most cases, tumors in the mice questions that would otherwise not beare more similar to the patient tumor theyGRADING SYSTEMpossible; for example, how cells of thecame from than any two tumors from twoTumors are classified by grade immune system interact with tumor cells. different patients. As such, tumorgraftsinto more or less aggressive. can also provide personalized models ofHigher grades correspond to The Largest Avatar kidney cancer (avatars). More than 1,400more aggressive tumors. The Program Worldwide? patient tumors have been transplanted intoInternational Society of Urological Tumors from patients are transplanted intomice. This resource is likely the largest inPathology grades ccRCC from the kidney of immunocompromised mice.the world.1 to 4. Grading is based on the Under the microscope, these tumorgraftsImportantly, these tumorgrafts alsoappearance of the cell and, in maintain the mutations, gene activationpreserve kidney cancers drug respon- particular, of a component of the siveness. To evaluate this, scientistsnucleus called the nucleolus. The treated mice bearing tumors with drugsnucleus is where the DNA and such as sunitinib. With help from thegenetic infrastructure are stored. It Pharmacokinetic Core Facility, dosing wasis typically in the center of the cell. adjusted to match blood levels in patients.The nucleolus is a spot within Kidney cancer tumorgrafts responded tothe nucleus. The more prominent sunitinib and other drugs active againstthe nucleolus, the higher the kidney cancer, but not against drugsgrade. The nucleolus is necessary previously shown to be inactive in patientsfor protein manufacturing in cells. with kidney cancer. These studies estab- Tumors with sarcomatoid features lished a proof-of-principle for the use ofare considered grade 4.tumorgrafts in programs to evaluate newWith support of the SPORE, Live biobank samplesdrugs against kidney cancer in patients,Maralice Conacci-Sorrell, Ph.D., a are preserved in liquidsuch as PT2399 (see page 37). In addition,cell biologist, is investigating the nitrogen tanks atthey have been used to test candidate -320 degrees F (-195Patient tumors are transplanted into mice tounderpinnings of nuclear grade.degrees C). generate avatars. drugs emerging from chemical screens; 66 67'