Cancer Cell Biology Research Program

Cancer Scientific Research Programs Cancer Cell Biology Research Program
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Cancer Cell Biology Research Program

At Perlmutter Cancer Center, scientists in our Cancer Cell Biology Research Program define the detailed molecular mechanisms whereby normal cell signal transduction and metabolism are dysregulated, which may lead to cancer and help it progress. Our research teams in this program aim to create new methods for diagnosing and treating cancer.

Our investigators collaborate to elucidate the role of protein modifications in regulating the three key dimensions of cellular life: survival, proliferation, and differentiation. They characterize signaling pathways regulated by oncogenes and tumor suppressors, including lung, colon, pancreas (KRAS), NRAS, melanoma (BRAF), cutaneous squamous cell carcinoma (NOTCH1), neurofibromatosis and melanoma (NF1), and lung (Keap1). Their studies are designed to lead to anti-cancer drug discoveries, and they also study cancer cells and their interplay with the tumor microenvironment related to metabolism.

Cancer Cell Biology Research Areas

The Cancer Cell Biology Research Program tackles major challenges in modern cancer research in several ways, including the following:

  • obtaining a precise, comprehensive map of signaling and metabolic pathways that control cancer cell properties, therapeutic response, and resistance
  • designing and synthesizing clinical-grade biologics and small molecules with drug-like properties that address “undruggable” targets
  • identifying biomarkers that identify patients most likely to benefit from specific treatments
  • translating promising concepts into investigator-initiated trials

Knowledge of tumor cell biology has led to many recent advances in cancer treatment, particularly new targeted therapies. Newly designed specific, potent, and bioavailable inhibitors work against frequently mutated and/or hyperactivated kinases, nuclear receptors, and metabolic enzymes and are now approved for the treatment of genetically defined cancer subtypes.

Yet therapeutic success is still relatively limited. Some biomarker-selected patient groups remain unresponsive to targeted agents, such as farnesyltransferase inhibitors in KRAS-mutant tumors and BRAF inhibitors in BRAF-mutant colon cancer. In these cases, even when initial responses are rapid and complete, resistance almost always occurs, such as in BRAF inhibitors in BRAF-mutant melanomas.

Targeted inhibitors have also become useful tools to probe signaling networks and further inform our understanding of cancer cell biology. Analyses of patient tissues collected pre- and posttreatment, or after resistance develops, have shown us new survival pathways and vulnerabilities, suggesting new strategies to prevent, bypass, or overcome therapeutic resistance.

Much work remains to extend the promise of personalized cancer medicine to most patients.