It may seem ironic, but death is critical to life. Apoptosis, the programmed death of cells that are irretrievably damaged or no longer useful, is necessary for organisms to develop properly and survive.
Cancer cells may have acquired mutations that thwart the apoptotic machinery, enabling them to proliferate uncontrollably. Another process frequently disrupted by mutations in cancer cells is senescence, a genetic death that allows damaged cells to live but prevents them from propagating.
Scott Lowe explores the genetic and molecular machinery of apoptosis and senescence to understand how genes control these processes in normal cells. He hopes to learn how mutations in these genes affect tumor development and tumor-cell responses to cancer therapies.
His work has shown that the antitumor effects of many chemotherapeutic drugs depend on their ability to activate apoptosis or senescence. As tumors evolve to circumvent the effects of such drugs, drug resistance may arise.
Lowe's work concentrates on an important regulator of apoptosis, called p53, a protein mutated in half of all human cancers. His studies revealed how p53 triggers apoptosis and how its mutations can promote drug resistance.
He developed mouse models of cancers to study the complexities of tumor evolution and resistance to chemotherapy, and more recently, has incorporated new genomic technologies to gain insights into the molecular basis of these phenomena. Studying these models has improved understanding of why a treatment may cure some patients but not others.
His studies have yielded insights into the process of senescence in normal cells and how anticancer drugs can induce it in tumors.
Lowe's future studies will aim to identify components of the apoptosis and senescence machinery and determine how they interact to suppress tumor growth. As in past studies, he will apply these findings to developing improved cancer treatment and methods of overcoming drug resistance.