Hopkins doctor awarded Breakthrough Prize

When the Egyptians first stumbled upon cancer more than 3000 years ago, they simply wrote: “there is no treatment.”

It was this formidable foe that Bert Vogelstein faced when he decided to pursue a career in medicine. Vogelstein, director of Ludwig Center for Cancer Genetics and Therapeutics at the Hopkins School of Medicine, was recently awarded the $3 million Breakthrough Prize in Life Sciences.

When Vogelstein started his career, no one knew how cancer delivered its wrath.

It begins as a small, seemingly insignificant mass that arises under the victim’s skin, lodges itself in an airway, or emerges on the surface of an organ. Surreptitiously, the mass grows into a larger tumor and begins to realize its destructive potential, interfering with the routine physiological functions of its surroundings while devouring all available nutrients.

As the tumor develops, it extends its roots into the bloodstream, giving it access to the abundant nutrients in the blood and also the opportunity to metastasize, or spread to other areas. Slowly but surely, the malicious tumors and cancerous cells conquer the rest of the victim’s body, leading often to death.

“We had little idea what the basis for cancer was,” Vogelstein said. “There were many theories, but little hard evidence.”

Despite centuries of scientific advances after the Ancient Egyptians, until the twentieth century the question remained: how does cancer make its way into the human body?

In search of a fruitful direction, Vogelstein devised novel experimental techniques to monitor the genome of cancer at its various stages of development. Of all the types of cancer, he took particular interest in colon cancer.

“Our study has been focused on colon cancers,”Vogelstein said. “The reason we chose them is because they progress through a well-defined series of tumors, starting from small, benign tumors and progressing finally to large, malignant tumors.”

Through this approach, Vogelstein and his team made an astounding discovery in 1988. They found that the mutations of certain genes are responsible for the progression of cancer. The acquisition of a sequence of these genetic mutations over time transforms a healthy cell into a malignant cancer cell.

In one study, the mutation of a particular gene, TP53, was identified in the genomes of a wide array of cancers. Further investigation revealed that the TP53 gene is a blueprint for a protein 53, or p53, a molecule in the human body now called “the guardian of the genome.”

This particular protein performs a crucial function: it prevents cells with significant genetic damage from dividing and growing. By facilitating the repair or death of cells with damaged genetic material, p53 suppresses the development of any potentially unhealthy cells.

However, once its own blueprint is mutated, p53 is no longer produced. In the absence of the guardian, unhealthy cells with significant genetic damage have a greater chance of surviving and passing on the mutated genome to a new generation of cells. These mutated cells become the precursor to a malignant outburst of cancerous cells.

Vogelstein’s discovery, now taught in classrooms and lecture halls across the world, illuminated a way forward for cancer research. Since then, many genes that are functionally similar to TP53, now called tumor suppressor genes, have been found. In addition to advancing the basic understanding of cancer, Vogelstein’s work has also been transformed into potent tools in the war against cancer.

In one instance, researchers at the Hopkins School of Medicine designed an upgraded, more sensitive version of the pap smear to detect genetic mutations specific to ovarian and endometrial cancers. Therapeutic interventions targeted at cancer-specific genetic mutations are also under development, opening a promising door to more effective treatments.

Perhaps, at some point in the future, we can erase the Egyptian’s pessimistic outlook and confidently say, “Yes, we can cure cancer.”