Outsmarting Cancer – From the War on Cancer to the Cancer Moonshot

On May 25, 1961, President John F. Kennedy announced, before a special joint session of congress, the dramatic and ambitious goal of sending a man safely to the moon before the end of that decade. This decision let to an enormous effort and expenditure, resulting in Project Apollo and the first manned moon landing in 1969.

Only a few years later, on December 23, 1971, President Richard Nixon declared a national “War on Cancer.”  On that day Nixon signed the National Cancer Act, allocating US $ 1.5 billion over three years for cancer research and control declaring: “I hope that in the years ahead we may look back on this day and this action as being the most significant action taken during this Administration.”

However, while the National Cancer Act increased the priority of cancer research in the federal budget and established a model of public-private cooperation built around a nationwide network of research laboratories and cancer centers, Nixon’s war strategists mistakenly assumed that, just like it was possible to put a man on the moon in less than a decade, a new approach to find a “cure” for cancer would be feasible and results would be tangible – clear and definite  – within just a few years.

What ensued following Nixon’s deceleration of war not a blitzkrieg against the dreaded disease, but a long lasting trench warfare. And history has shown that, while we’ve won countless battles, cancer is probably one of the most resilient and recalcitrant enemies ever.

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Some cancers that were once invariably fatal, including various forms of childhood leukemia, are now, in the vast majority of cases, curable.  Data published by the American Cancer Society confirms that in other cancers, such as kidney cancer, the five-year survival rate has increased from about 50% in 1971 to more than 70% today.  In the same period, the five-year survival rate of colon cancer increased from 52% to more than 66%. Furthermore, rates of dying of a number of cancer, including  breast, liver, lung, prostate, and several other cancers have, for the past 20 years declined. But despite these successes, after nearly 45 years, most experts would agree that, in general, we’re losing the “War on Cancer.” One key reasons is a chronic lack of funding for (academic) research.

And herein lies the dilemma. In an ideal world, every academic researcher would have access to sufficient funds to support their research. However, while the need to find a “cure” for cancer is real and immediate, the fact is that many researchers spend only a small fraction of their time in a laboratory.  Instead of important, lifesaving, research, they are obligated to write complex grant proposals to fund their work so they can pay for research materials and staff salaries. And while grant money is absolutely necessary, each grant application may take an experienced, seasoned, investigator more than hundred (!) hours to complete.

A shocking statistic shows that the National Cancer Institute’s average funding rate, defined as the percent of applications awarded compared with the total number of applications received, is less than 10%.  This means that, on average, only 10 out of every 100 grant applications submitted by academic researchers are successful. On average, ninety percent (!) of all requests are rejected, leading to a staggering loss of time not spent in completing research, stifling innovation.[1]

And yet, without proper (federal) funding and without writing complex grant proposals, (academic) research is impossible – and the “War on Cancer” lost.

The good, the bad and the ugly
A closer look at incidence and survival data from 1975-2013, obtained from the Surveillance, Epidemiology, and End Results (SEER) Program, shows that while there have indeed been major advances in cures for some childhood cancers, the overall death rate for cancer has remained almost unchanged over the past several decades.  In spite of the development of targeted therapies  and personalized medicine that have helped prolong life, improved prevention, and numerous advances in early detection, the overall gains in being able to “cure cancer” are minimal.[2]

And the data further shows that, in the United States, cancer is on track to overtake cardiovascular disease as the leading cause of death.  Shockingly, with the increasing effort that has been spent in search for a cure, the number of overall cancer deaths has only continued to increase. This year, 8 million people worldwide [3] will die from cancer related illnesses, including 600,000 people in the United States. [4]

So, why is this happening, and why have we not made the same progress in the treatment of cancer as we have made in the treatment of, for example, cardiovascular disease? This question is not easy to answer. However, realizing that cancer is not a singular disease, but is in fact more than 200 different diseases, each with unique characteristics, biologies, as well as strengths and vulnerabilities, may, in part, help us to understand that cancer is infinitely more complex than most other diseases.  This may also help us to understand that a simple answer – and a simple solution to find a cure – may for now still be unattainable and illusive.

A growing number of survivors
But it is not all doom and gloom. And it would definitely be disingenuous to call Nixon’s war on cancer failure. A study by Shirley M. Bluethmann, PhD, MPH, a cancer prevention fellow at the National Cancer Institute in Bethesda, Maryland, shows that there are approximately 15.5 million cancer survivors in the United States (in 2016). Sixty-two percent of these patients is 65 or older. In the same study Bluethmann and her co-workers project that by 2040 there will be at least 26.1 million cancer survivors of which 73% will be 65 or older.[2]

The results of Bluethmann‘s study are also reflected in the data from SEER and the American Cancer Society, showing that the overall lifetime risk^∗ of developing cancer in the United States, approximately 42%, is slowly decreasing.  The data in the SEER database further shows that the lifetime risk of dying from cancer is just under half of that (22.6%).  Expressing the lifetime risk of developing or dying from cancer as odds shows that 1 in 2 people living today will develop cancer in their lifetime, while 1 in 4 will ultimately die of the disease.[5]

Bluethmann’s data is, however, addresses a critical factor.  Older adults are generally understudied, presenting challenges in delivering effective and age-appropriate care. For example, co-morbid conditions in many older adults may make them ineligible to participate in clinical trials. As a result, we lack key data which would inform us how geriatric populations would react to or benefit from novel anticancer treatments and interventions. And adequate funding to study this – to find evidence based answers – is lacking.

A Cancer Moonshot
In April this year, following an initial announcement during President Barack Obama’s State of the Union address in late January, the National Cancer Institute, part of the National Institute of Health, established of a Blue Ribbon Panel of scientific experts, cancer leaders, and patient advocates expected to guide the scientific direction and goals at National Cancer Institute of Vice President Joe Biden’s National Cancer Moonshot Initiative.

During his State of the Union address, Obama announced that the Cancer Moonshot would would be “for the loved ones we’ve all lost, [and] for the families we can still save.”

In the President’s plan, the National Cancer Institute scientific road map, outlined by the members of the Blue Ribbon Panel, would be but one component of the Cancer Moonshot’s broader effort focused on accelerating progress on the prevention, diagnosis and treatment of cancer.

Announced and inaugurated with much fanfare, the panel’s goal was to provide scientific guidance from Key Opinion Leaders/Thought-leaders in the cancer community would serve as a working group of the presidentially appointed National Cancer Advisory Board.

Missed opportunity?
While the concept and intention of President Obama Cancer Moonshot initiative is definitely praiseworthy, much of its initial execution has, according to some research experts, been fraught with avoidable missteps as well as the infinite complexities of uniting largely independent government departments, from the National Institute of Health and the Food and Drug Administration to the Department of Veterans Affairs and the Department of Energy as well as a  kaleidoscope of federal institutes and agencies.

Among the many observed missteps is the fact that the Cancer Moonshot was presented as a “National” – US-Centric – effort.  In an Op-Ed (“Missed opportunities for White House’s ‘moonshot’ cancer initiative“) published in The Hill, a U.S. political newspaper for (federal) lawmakers, Eric Rosenthal, a friend and contributor to ADC Review / Journal of Antibody-drug Conjugates, noted that the statement “Let’s make America the country that cures cancer once and for all,” was not only nationalistic but also negated the prevailing notion that cancer is a global, not just an American, disease and that finding a cure or – at least – finding a way to make the disease a more manageable, chronic, disease, requires the best and the brightest from around the world – working together in reaching that ultimate goal.

Another often heard concern is timing. The Cancer Moonshot was launched in the final year of the Obama administration. This means that Biden, who is the program’s engine, will have to relinquish his role as program manager in just a few months, raising questions whether the next administration will adopt the Cancer Moonshot initiative.

Nonetheless, earlier this week, the acting director of the National Cancer Institute, Douglas Lowy, M.D., accepted the recommendations of a Blue Ribbon Panel (BRP) on 10 scientific approaches most likely to make a decade’s worth of progress against cancer in just five years under the Cancer Moonshot.

This week the report was presented by the 28-member Blue Ribbon Panel to the National Cancer Advisory Board. The report, published this week in the journal Science, is roughly based on expert advice of more than 150 cancer experts who reviewed more than 1,600 suggestions from (academic) researchers and the general public.

“The bold but feasible cross-cutting initiatives in this report will improve outcomes for patients with cancer, prevent cancer and increase our understanding of cancer,” Lowy noted. “The National Cancer Institute stands ready to accelerate cancer research in the critical areas identified by the Blue Ribbon Panel.”

And Francis S. Collins, M.D., Ph.D., the director of the National Institute of Health added that: “Thanks to the coalescence of new scientific insights and technological innovations, cancer research is poised to make unprecedented advances.”  He added: “[These] approaches, identified by the Blue Ribbon Panel, offer exceptional promise in tipping the odds in favor of cancer patients.”

And just like Kennedy’s Apollo Program, to be successful, the Cancer Moonshot required enormous effort matched by a colossal expenditure.

More Money – Better Treatments?
But does such a colossal investment in the Cancer Moonshot really result in better patient outcomes?  Have we, indeed, reached a point in time where a little extra money is like waving the magical wand that wipes out cancer? The simple answer is that we don’t know. How can we clearly demonstrate that increasing our investment in cancer research will result in better treatments and better patient outcomes? How much money is required?

Following the signing of the National Cancer Act, federal funding for cancer research increased dramatically, resulting in the National Cancer Institute becoming the largest, single source of support for cancer research, accounting for nearly two-thirds of funding from all sources in 1974. Over time, however, the funding base has broadened. And while the National Cancer Institute’s budget has, over the years, steadily increased, other sources have expanded even more. The private sector pharmaceutical companies, for example, having no real budgets for cancer research in the early 1970s, radically increased their cancer research budgets as well. And these private sector funders have, in the past 45 years, collectively spent nearly a trillion dollars (in 2016 dollars) in attempts to develop novel anticancer therapeutics.** [6]

So, do the new technologies and research advances coming on-line now as a results of these investments have the ability to offer a definite  cure, or, at least, make cancer a chronic, manageable, disease?  How does the funding proposed under the Cancer Moonshot increase federal funding compare to private sector investments? And, what’s more, are we choosing to spent our fund on research projects that can really make a difference? In other words, are we fighting the right war?

A reactive approach
In an Op-Ed published earlier this year in our journal, Amit Kumar, Ph.D, the Vice Chairman of ITUS Corporation and Executive Chairman of Anixa Diagnostics Corporation and an expert in cancer diagnostics with over 20 years of experience in cancer research, argues that “our approach to cancer has been almost entirely reactive in nature.” Kumar explains that today we wait until cancer symptoms appear, which, in many cases is after the cancer has become advanced, and then attempt a cure. In his opinion, this makes finding a cure more difficult and complex.  He correctly reasons that, as a consequence of our own, narrow-minded, interpretation of how we should treat malignancies, it is not that the war against cancer has been lost, it is that we have been fighting the wrong war.

While the development of novel, targeted and personalized anticancer drugs, such as antibodies, related antibody-drug conjugates and novel immunotherpies, is immensely important, these biological drugs are enormously expensive and are effective only for a relatively small number of patients. So, what are we missing?

Kumar points to the simple fact that early detection is one way to really improve survival.  He points out that the overall, five-year survival rates for patients diagnosed with stage 3 or stage 4 breast cancers, cervical cancers, ovarian cancers, prostate cancers, and colon cancers are 28%, 16%, 28%, 28%, and 13% respectively. In contrast, the five-year survival rates for patients diagnosed at stage 1 or stage 2 of the same five cancers are 99%, 91%, 92%, 100%, and 90%, respectively.[7]

Early diagnosis increases the chance for full recovery.  An added benefit is that following early diagnosis, treatment is often simpler and the medicines we use to treat are less aggressive and generally more effective, which in turn, increases the health related Quality of Life (hrQoL) of patients.

But early diagnosis also makes treatment more affordable and costs effective. For example, according to a report published in the United Kingdom for Cancer Research UK, the overall, costs of treatment for stage 3 and 4 colon, rectal, lung and ovarian cancer costs the UK’s National Health Service nearly two and a half times the amount spent on treatment of stage 1 and 2 of the same cancers.

The benefits of early diagnosis are not only seen in oncology and hematology. Just as our current approach to cancer, many years ago the standard approach to cardiovascular disease was to wait until the patient exhibited signs of the disease.  But when our approach – our strategy – to the treatment of heart disease changed from interventional to one of prevention and early detection, death rates decrease. The result has been a 60% decrease in heart disease related deaths since 1971.[8][9][10]

With the advent of novel molecular technologies, research in early-detection has received more attention.  These new technologies can identify cellular changes at the level of the genome or proteome, making new diagnostic procedures more effective.

But early diagnosis is, in itself, not a divine panacea. It’s not necessarily an unalloyed good, a cure-all or universal remedy.  Unrestrained (early) diagnosis may lead to treating abnormalities that in actuality may never result in disease that affects the patient.  This, in turn, may result in unnessary patient anxiety and, potentially, unwarranted treatments that could put a patient at risk of complications. [11]

Kumar concludes that today we are at an inflection point in the fight against cancer with many potential changes on the way from what some might consider to be disruptive technologies in the way we diagnose and treat cancer.

Funding remains imperative
And herein lies another, crucial, problem for Cancer Moonshot enthusiasts. While the National Cancer Institute’s advisory board, has approved the Blue Ribbon Panel‘s recommendation, the United States Congress now needs to come up with the federal funds to pay for the efforts required to further develop and successfully implement these disruptive strategies.

But are lawmakers in the United States Congress really motivated to increase funding of medical research following 12 years of flat budgets —as it did in December 2015 with its $2 billion increase to the National Institutes of Health?  Research advocates doubt their sincerity and question the courage of partisan lawmakers to make this happen.

While a Senate committee has indeed approved a 6% increase of the National Institute of Health‘s budget, a US $ 2 billion jump to US $ 34.1 billion, a  separate House panel has only approved a 4% increase.  But these budgetary increases are to boost Alzheimer’s disease research and the President’s Precision Medicine Initiative, and are not to realize the recommendations made by the Cancer Moonshot Blue Ribbon Panel.  Neither bill contains the US $ 680 million requested by the White House for  the Obama administration’s Cancer Moonshot program.

Given the political rhetoric and partisan bickering in Washington, the expectation is that funding remains elusive. Practically speaking, (academic) cancer researchers may, as a result, not be able to start new programs or benefit from suggested budgetary increases envisioned in some preliminary appropriations bills as long as final action to approve these bills is not taken.  And this may severely handicap the Obama administration’s Cancer Moonshot.

But there is more.

In his Op-Ed, Rosenthal, quoted earlier, made it clear that the Cancer Moonshot would have been more sustainable if it had bipartisan support at the outset, especially since the importance of cancer research is not limited to just one side of the aisle. Unfortunately, the concern is that with the present Cancer Moonshot program a highly partisan approach may, sooner or later, defeat the President’s noble and virtuous goal of finding a cure for cancer.

However, for now, Jon Retzlaff, managing director of science policy and government affairs for the American Association for Cancer Research, praised the suggestions made by the Cancer Moonshot Blue Ribbon Panel.

Retzlaff noted: “We are hopeful that these recommendations are going to be so exciting that [the Republicans in] Congress will be looking to identify paths forward to fund the cancer moonshot initiative.”

The questions remains if such hope is really warranted. Is it based on the ability and the overarching desire of realizing a dramatic and ambitious plan or does this hope merely reflect unsustainable wishful thinking, which will, ultimately, be lost in a bureaucratic quagmire and political ill-will?

Time will tell.

^*Note: The individual lifetime risk of developing cancer or dying of the disease may be higher or lower than these numbers. This depends on a person’s particular, individual, risk factors.

** Note: The National Institute of Health, which includes the National Cancer Institute, is the world’s largest single funder of biomedical research and their budget is roughly one-third of all spending on biomedical research and development in the United States, private and public sector combined.

October 21, 2016 | Corresponding Author: Peter Hofland | doi: 10.14229/jadc.2016.09.10.001

Received: September 6, 2016 | Published online September 10, 2016 | This article has been submitted for peer reviewed by an independent editorial review board.