DAVIS—UC Davis Professor Jay Rosenheim researches, lectures, and publishes his work on predator-prey interactions, but he's now targeting another kind of predator: an insidious foe that can be as stealthy and powerful as it is terrifying.

A six-letter word: Cancer.

But it's a foe that society eventually will defeat, declares Rosenheim in his newly published article, Short- and Long-Term Evolution in Our Arms Race with Cancer: Why the War on Cancer is Winnable, in the journal, Evolutionary Applications.

“Human society is engaged in an arms race against cancer, which pits one evolutionary process – human cultural evolution as we develop novel cancer therapies – against another evolutionary process – the ability of oncogenic selection operating among cancer cells to select for lineages that are resistant to our therapies,” wrote Rosenheim, a 28-year member of the UC Davis Department of Entomology and Nematology faculty who has battled chronic myeloid leukemia (CML) for the past seven years.

Despite individual setbacks, society's “cumulative progress in developing anti-cancer therapies is giving us a bigger and bigger lead in our arms race against cancer,” the professor wrote. “That's why the war on cancer is winnable.”

In the 2600-word, well-referenced piece, Rosenheim frames his argument by citing that “it is helpful to begin with more typical evolutionary arms races that occur between human populations and various injurious organisms whose populations we perennially attempt to suppress. Injurious organisms include those that attack us directly (human parasites and pathogens); organisms that vector pathogens to human hosts; organisms that compete with our crops (weeds) or that directly attack our crops or domesticated animals; and organisms that attack or infest our homes. To suppress these disease or pest populations, we deploy a huge array of drugs, pesticides, and other suppressive measures on a global scale (REX consortium 2012). In each case, this sets in motion an evolutionary arms race, pitting one long-term evolutionary process (human cultural evolution, as we invent new control tactics) against another long-term evolutionary process (evolution of resistance by natural selection in the populations of the injurious organisms).”

He pointed out that “Cancer cells have a powerful ability to evolve resistance over the short-term, leading to patient relapse following an initial period of apparent treatment efficacy. However, we are the beneficiaries of a fundamental asymmetry in our arms race against cancer: whereas our cultural evolution is a long-term and continuous process, resistance evolution in cancer cells operates only over the short-term, and is discontinuous: all resistance adaptations are lost each time a cancer patient dies. Thus, our cultural adaptations are permanent, whereas cancer's genetic adaptations are ephemeral. For this reason, over the long term, there is good reason to expect that we will emerge as the winners in our war against cancer.”

Although the professor does not mention his own cancer diagnosis in the article, he is open about the disease, both with students and his peers. “Prior to 2001, CML was a very bad disease, with little chance of survival beyond three to five years,” Rosenheim related. Then in 2001, the Federal Food and Drug Administration approved imatinib, the first of the “targeted chemotherapies.” Time magazine hailed it as “the new ammunition in the war against cancer” in its May 28, 2001 cover story.

“Although it did not create a cure, it allowed most patients to manage the disease with minimal side-effects of the treatment,” Rosenheim said. “But, for some patients, the cancer evolved resistance to imatinib.  Researchers developed a series of second generation, and now third generation, drugs, that give nearly all patients a series of effective options if the initial drugs fail.  I am one of the many patients to benefit from the multiple effective drugs. Imatinib didn't really work for me, perhaps because of resistance; but a second-generation drug has worked, and continues to work, exceptionally well.” 

“CML remains one of the most dramatic successes of targeted chemotherapies for cancer, and it is also now an equally dramatic example of how our cumulative progress in developing anti-cancer therapies is giving us a bigger and bigger lead in our arms race against cancer.  The result is that more and more CML patients live out their full lives.  And, in the meantime, the research oncologists are working now on how to move to the next step of an outright cure for CML.”

In the article, Rosenheim concludes: “The war on cancer has struggled during its first four decades to make major inroads on cancer mortality. This is, to a large degree, due to cancer's prodigious short-term ability to evolve resistance to our therapeutic interventions. But, with our ability to mount a sustained, continuous process of cultural evolution, in which every increase in our knowledge and every therapeutic tool devised is permanently retained, it was reasonable to expect that the tide would eventually turn. The Achilles' heel of cancer is that it cannot retain its resistance-conferring adaptations across different hosts. Whether with small, incremental steps, or large, dramatic leaps forward, the cumulative progress in our ability to treat cancer will, in the end, reveal the war on cancer to be winnable.”

UC Davis distinguished professor Bruce Hammock, who holds a joint appointment with the UC Davis Department of Entomology and the UC Davis Comprehensive Cancer Center, said that “this article makes a strong argument that our physicians need a full tool box for the war on cancer, and it provides real hope that this expanded tool box will lead to our winning the war.”  

“There are few adults not touched directly or indirectly by cancer,” Hammock said. “Based on expanding fundamental knowledge of biology. there are numerous new cancer treatments. Yet it seems cancer often wins in the end.  From an evolutionary perspective the Rosenheim article gives us hope that cancer can be beaten by a multi modal approach because unlike pathogens, cancers must start their evolutionary process fresh with each patient.”

Longtime breast cancer surgeon and cancer awareness advocate Dr. Balazs “Ernie” Bodai, retired chief of surgery at Kaiser Permanente, Sacramento, and now director of the Breast Cancer Survivorship Institute, described the article as “both intriguing and timely.” 

“Indeed, cancer battles are being won, but the war is far from over and goes on,” said Bodai, a 1977 UC Davis School of Medicine alumnus, a UC Davis clinical professor of surgery, and a nominee for the 2015 Congressional Gold Medal. Noted for his cancer awareness drives, he convinced Congress and the U.S. Postal Service to issue the Breast Cancer Research Stamp and is currently introducing a “global stamp” to raise worldwide awareness.

“Each year 1.6 million Americans are diagnosed with cancer,” Bodai said. “Worldwide, 14 million cancer diagnoses will be made, with a death rate which is unknown, due to poorly reported statistics and terminal events. We do know that 600,000 deaths annually are due to malignancies in the United States, exceeded only by cardiovascular disease as a primary cause of death.”

Turning to the Rosenheim article, Bodai noted “I appreciate the intricacies of our bodies, environmental factors, potential adaptations, mutational potentials as they may not only play a role, but potentially, rule the development of carcinogenic activities. The author and I share two common characteristics: first, we are both cancer ‘survivors'--a term I am not particularly fond of as it may imply that we were successful, as others were not through no fault of their own--and second, it appears that we share a deep commitment to fight cancer on all fronts. The hypothesis of a mutagenic potential of cancer cells to overcome the effectiveness of current and future potential treatments is alarming and should be of concern to all, especially future generations.

“The ongoing research to find a cure for cancer is promising. It will take a multidisciplinary approach as demonstrated by the department from which the author originates. Charge on my colleague, charge on!”

Cancer research scientist Dipak Panigrahy of Harvard University's Judah Folkman lab, considered one of the country's best cancer treatment labs, said that "Cancer has already or will impact every person. Dr. Rosenheim's exciting article provides the public compelling evidence on why cancer patients should never give up hope. This expert analysis on our race with cancer gives a unique and comprehensive review of recent promising cancer treatments. Despite the setbacks and challenges of cancer research, this article gives us hope we will eventually win vs. cancer.” 

Cancer research scientist Paul Henderson of the UC Davis Division of Hematology and Oncology, and the UC Davis Comprehensive Cancer Center, who researches which technologies will best benefit cancer patients, said the paper “is an excellent summary of the history of cancer care and the implications for our sustained effort as a society to overcome resistance to therapy and win the war on cancer.” 

Rosenheim, who joined the UC Davis entomology faculty in 1990, is a fellow of the American Association for the Advancement of Science, a member of the Entomological Society of America,  and a co-founder of the UC Davis campuswide Research Scholars Program in Insect Biology. Highly honored for his teaching, he received the Academic Senate's Distinguished Teaching Award for Undergraduate Teaching and the Associated Students' Excellence in Education Award.

Link to Article:
Short- and Long-Term Evolution in Our Arms Race with Cancer: Why the War on Cancer is Winnable

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