Research points to potential for patient-specific cancer therapies

July 1, 2015

WASHINGTON, D.C. — Researchers are working to better understand cancer as an organismal disease and to better comprehend its physiology — the science of how it functions — and its environment and interactions in the human body. But, despite decades of advances in research, treatments, early diagnosis and prevention, cancer remains "one of the significant challenges in the history of medicine."

Dr. Siddhartha Mukherjee
Photo credit: Evelyn Hockstein/© CHA

That is according to oncologist, cancer researcher and acclaimed author Dr. Siddhartha Mukherjee, who traced the history of cancer and the hunt for cures in his June 8 keynote address at the Catholic Health Assembly. Mukherjee opened the session with video excerpts from a recent PBS documentary based on his Pulitzer Prize-winning book The Emperor of All Maladies: A Biography of Cancer. The videos underscored the emotional and physical toll of cancer, and established human context for the scientific overview of efforts to understand, combat and cure the disease which followed.

From roughly the 1970s to 1990s, cancer was considered a "disease of genes," and much research focused on understanding how and why normal cells mutate to become rapidly multiplying cancer cells. Mukherjee described the normal growth of cells and the hyperproliferation of cancer cells as "conjoined twins" and said for that reason cell growth-stopping therapies developed at the time were limited because researchers hadn't been able to find a mechanism to distinguish between normal and abnormal cells.

In The Emperor of All Maladies Mukerjee notes that the results of discoveries made in the 1950s and 1960s began to bear fruit between 1990 and 2005, a period when cancer death rates fell nearly 15 percent. As bench scientists delved into the metabolism and physiology of cancer, antismoking campaigns and efforts to promote cancer screening to detect early stage, even premalignant, colon, cervical and breast cancers, along with refinements in chemotherapy regimens and other therapies began to pay off.

From 1990 to 2010, researchers came to understand cancer as "not just a disease of cells, not just a disease of genes," but a disease of genomes, which is an organism's complete set of DNA, including all its genes. Mukherjee told the assembly audience that normal cells undergo a series of mutations before becoming cancerous cells, with hundreds of gene mutations in any individual cancer. He said doctors and researchers have never encountered a human disease that has the same level of diversity as cancer.

Rather than searching for one elegant solution to fighting cancer, "we have begun to address this piece by piece by piece," he said.

Researchers are working to better understand the role of the immune system and how to harness it to fight certain types of cancer, as well as how to disrupt certain cancers by fighting them at the molecular level.

Mukherjee listed 10 hallmarks of cancer, involving pathways and acquired capabilities that differentiate cancer cells and their environment from normal cells in a healthy subject. These include tumor-promoting inflammation, genome instability and mutation, and the ability to fend off destruction by the immune system and evade growth suppressors in the body. He said combining therapies that address hallmark characteristics of cancer cells is likely to yield "vast success" in the next phase of cancer treatments.

He said the cancer therapy research model has shifted from "try and try again" to "fail fast and early." Researchers are culling potential candidate pools for cancer therapy trials to identify individuals most likely to respond to specific therapies. This approach supports a new direction toward personalized precision therapies designed to be the best line of treatment for individual cancer patients.


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