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Cancer Care Fundamentals for Frontline Clinicians

By Kristen Schepker, Assistant Editor

Today's rapidly growing population of cancer survivors obliges all frontline clinicians to develop a better understanding of this complex disease, and to learn how to support patients both during and after chemotherapy, radiation and other forms of treatment.nalini chilkov

Improvements in early detection and better therapies have contributed to a continued increase in the number of patients experiencing life after cancer. Many now live for decades following an initial cancer diagnosis, and the American Cancer Society projects that the number of cancer survivors will increase from 14.5 million in 2014 to 19 million by 2024 (Am Soc Clin Oncol. J Oncol Prac. 2015; 11(2): 79-113).

That's certainly a positive trend, but the ensuing journey through survivorship is not an easy one, says Nalini Chilkov, LAc, OMD, the founder of the American Institute of Integrative Oncology Research and Education. Eliminating tumors is one thing. Becoming healthy is quite another, explained Dr. Chilkov at the recent Clinical and Scientific Insights (CASI) conference in San Francisco. 

Life after cancer is often rife with long-term physical effects of treatment, as well as psychological challenges like fears of recurrence. The path can be even rockier for children with cancer, who may be at an increased risk of developing subsequent cancers and who often endure treatment-related side effects for many years after treatment has been completed.

Primary care practitioners--especially those with a holistic orientation--can play a vital role in pushing the model of long-term cancer care beyond simply "absence of the disease" and toward optimizing  health and wellbeing, says Dr. Chilkov,  author of the book 32 Ways To OutSmart Cancer: Create a Body in which Cancer Cannot Thrive.

But, as the authors of a 2014 study found, there is a glaring education gap. Awareness of the late and long-term effects of chemotherapy is limited among primary care physicians (Nekhlyudov, L. et al. J Oncol Pract. 2014; 10(2): e29-e36).  "Education for all providers caring for the growing population of cancer survivors is needed," the researchers concluded, an observation that Chilkov reiterated throughout her CASI lecture.

The "Hallmarks of Cancer"

A central piece of that education, she proposed, is to understand the unique differences between cancer cells and "normal" healthy cells.

For guidance on this subject, Chilkov pointed to a landmark paper, "The Hallmarks of Cancer," published by Douglas Hanahan and Robert Weinberg in January 2000 in the journal Cell. Hanahan and Weinberg assert that the many complexities of cancer biology can be traced to a small number of specific qualities that distinguish tumor cells from healthy cells (Hanahan, D. & Weinberg, R. Cell. 2000; 100(1): 57–70).

hallmarks of cancerThey propose that most, if not all, types of human cancer share six key molecular, biochemical, and cellular traits:

1.) They stimulate their own growth ("self-sufficiency in growth signals");

2.) They're resistant to inhibitory signals normally intended to block cell proliferation ("insensitivity to growth-inhibitory (antigrowth) signals");

3.) They resist programmed cell death ("evasion of programmed cell death (apoptosis)");

4.) They have an unlimited ability for multiplication ("limitless replicative potential");

5.) They can grow new blood vessels ("sustained angiogenesis"); and

6.) They can both invade nearby tissues and also spread out to distant sites ("tissue invasion and metastasis").

These six core biological capabilities, the authors argue, "constitute an organizing principle for rationalizing the complexities of neoplastic disease."

In a 2011 update to their original publication entitled, "Hallmarks of Cancer: The Next Generation," Hanahan and Weinberg added new principles to their original list of cancer cell traits. The first, termed the "reprogramming of energy metabolism," highlights the ability of cancer cells to modify, or reprogram, cellular metabolism in order to most effectively support neoplastic proliferation.

The second, "evading immune destruction," defines cancer cells' capacity to evade immunological destruction, in particular by T and B lymphocytes, macrophages, and natural killer cells (Hanahan, D. & Weinberg, R. Cell. 2011; 144(5): 646-674).

Underlying these hallmarks, Hanahan and Weinberg explain, are two additional important characteristics: "genome instability," which generates the genetic diversity responsible for acquisition of these other hallmark traits, and "inflammation," which drives several of the other hallmark functions.

The Tumor Microenvironment

It turns out that many tumors are really good at recruiting normal cells to do their bidding. Hanahan and Weinberg note that cancers "...contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the 'tumor microenvironment.'"tumor microenvironment The biology of tumors can no longer be understood simply by enumerating the traits of the cancer cells but instead must encompass the contributions of the tumor microenvironment.

Dr. Chilcov explained that tumor cells and the surrounding connective tissue cells form "a sticky mat covering the surface of the tumor cells." Beneath this mat, tumor cells can "hide" from immune cells that would normally become activated and attack the offending cancer cells. In effect, its cellular camouflage.

According to researchers Diwakar Pattabiraman and Robert Weinberg, emerging tumors recruit a wide range of cellular components that can be classified into three main groups: 1) Cells of haematopoietic origin like T cells, B cells, and natural killer cells; 2) Cells of mesenchymal origin such as fibroblasts, myofibroblasts, mesenchymal stem cells, adipocytes and endothelial cells; and 3) Non-cellular components including proteins, glycoproteins and proteoglycans that make up the extracellular matrix (ECM).

Each of these components are present at varying proportions in solid tumors of different origins and at different stages of progression (Pattabiraman, D. & Weinberg, R. Nat Rev Drug Disc. 2014; 13(7): 497–512). Together, these elements comprise "a complex habitat involving myriad interactions between cell types and the ECM, each having a role in influencing tumor outcome."

In other words, cancer is not a "thing," it's a system.

This may sound theoretical, but it has direct practical significance, says Dr. Chilkov.

After a patient receives a cancer diagnosis, the first and most pressing medical objective must be to reduce that patient's tumor burden. In order to achieve this goal, it is critical that practitioners develop an awareness of the main components and functions of the tumor microenvironment. "The tumor microenvironment needs to be tended to," she urged, because "it contributes to every aspect of carcinogenesis."

Take inflammation, for example.  It can promote the emergence of various cancer cell traits by supplying "bioactive molecules to the tumor microenvironment, including growth factors that sustain proliferative signaling, survival factors that limit cell death, proangiogenic factors, extracellular matrix-modifying enzymes that facilitate angiogenesis, invasion, and metastasis, and inductive signals that lead to activation of [epithelial-mesenchymal transition] and other hallmark-facilitating programs." Downregulate inflammation, and you make it harder for cancer to get what it needs to grow.

Attention to the tumor microenvironments has already contributed to a shift in the way some oncologists approach the treatment of cancer. Researchers have shown that, "compared to chemotherapy alone, targeting tumor cells as well as key components of the tumor microenvironment significantly improve[s] the clinical outcomes of patients." (Feng, G. et al. Curr Cancer Drug Targ. 2014; 14(1): 30-45).

Starve the Tumor, Nourish the Patient

After reducing tumor burden, Chilkov says, a physician's second goal must then be to "nourish the patient."

The idea here is to "create environment that is inhospitable to the development, growth, proliferation, and spread of tumor cells," she said. This process, she adds, begins during cancer treatment and extends onward through survivorship.

She shared the story of a breast cancer survivor who came to her struggling with severe peripheral neuropathy. In working with her, Chilkov identified a number of underlying factors potentially contributing to the patient's neuropathy including multiple SNPs, high oxidative stress levels, high inflammation, and reverse omega fatty acids. Chilkov and her patient put together a plan that included acupuncture, and dietary guidance around how to "eat the rainbow" and choose anti-inflammatory foods. Within ten weeks, the patient's neuropathy disappeared.

Rather than treating the symptoms, Chilkov said, she focused on "transforming function" to establish the unique and optimal conditions for the patient's recovery and continued health.

Dr. Chilkov is certainly not alone in championing natural therapies as adjuncts to conventional medicine.

In 2006, Keith Block, MD posed the question, "Why Integrative Therapies?" in an editorial that appeared in the journal Integrative Cancer Therapies. In it, Block offers numerous examples of how therapies often defined as "complementary" or "alternative" may contribute to getting cancer patients better, if they are used strategically as part of a comprehensive program to improve the survival, as well as survivorship (Block, K. Integ Cancer Ther. 2006; 5(1): 3-6).

"It matters what you eat," Chilkov told the CASI audience, "because your food is talking to your genes." Some foods can epigenetically influence the expression of certain genes. "Phytochemicals are always multitaskers," she added.

As an Oriental Medical Doctor, Chilkov's approach to cancer care also incorporates targeted Chinese medicine interventions including acupuncture, moxibustion, and traditional Chinese herbal and food therapies.

The ultimate goal, she says, is not just to improve patients' life span but also their health span.

It's the responsibility of the oncology team to minimize tumor burden to the greatest degree possible in each case. But it is the responsibility of primary care practitioners to help individuals carve out their own paths to health and wellbeing. By leveraging what we now know about tumor biology and the factors that promote tumor growth, we can help people envision and actualize healthy life beyond cancer.

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Scientific American Calls Out FDA’s Media Malfeasance

By By Erik Goldman, Editor

The Food and Drug Administration uses a system of close-hold news embargoes and “Faustian bargains” to control when and how major media outlets report on the agency’s rulings and other activities, according to a recent article in the venerable Scientific American magazine.

EmbargoedIn his article titled, “How the FDA Manipulates the Media,” author Charles Seife describes how FDA press agents offer selected media outlets like CNN, CBS, NPR, the Wall Street Journal, and the New York Times exclusive access to hot stories on the condition that their reporters ONLY speak to FDA-vetted sources.

Scientific American obtained documents via the Freedom of Information Act that Seife says,“paint a disturbing picture of the tactics that are used to control the science press.”

Embargoes designed to regulate the timing of news stories are widespread throughout the media world, and have been for decades. Corporations use them, as do academic institutions, trade organizations, scientific journals, and government agencies.

Tacit Acceptance

In the simplest terms, the issuing party offers journalists “sneak peak” access to important news on condition that they agree not to publish the information before a certain date.

These so-called “close-hold” embargoes are the norm in the publishing world, and while some people have questioned the ethics of the practice, and many institutions—including the FDA have lip-service policies condemning it—there’s been a longstanding tacit acceptance of publication-date embargoes between journalists and news sources. Few media companies or media watchdogs have challenged it in any meaningful way.

Companies, agencies and institutions also use embargoes to channel news into certain media outlets to the exclusion of others. A news source simply offers advance information to handful of its preferred media companies, to the exclusion of others, thus giving the preferred outlet(s) the much coveted “exclusive” story.

The Scientific American article contends that the FDA has added a new dimension to the embargo process by offering preferred information access only to journalists who agree, beforehand, that they will not seek comment from anyone outside the agency’s chosen list of experts for a set period of time.

If a reporter breaks the agreement, the FDA simply threatens to exclude the offender from its official pool of insiders.

In effect, this lets the FDA control not only the timing of a story but also the way it is spun. By getting reporters to limit their inquiries, the agency can assure that news coverage will reflect the views of its experts and the agency’s stated—or unstated—intentions.

Siefe holds that use of embargoes of all shapes and stripes is on the rise not only by the FDA or other federal agencies, but by corporate and academic interests as well.

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DEA's Cannabis Catch-22: Expand Research, Maintain Criminality

By Kristen Schepker, Assistant Editor

Late last summer, the Drug Enforcement Administration (DEA) adopted a new policy designed to foster an increase in medicinal cannabis research. The Administration’s decision opens doors to a larger number of marijuana suppliers qualified to produce cannabis for scientific study, a shift that will arguably lead to broader and more comprehensive study of a drug which, despite widespread medical use throughout the country, remains highly controversial. 

Sublingual Immunotherapy Proves Effective for Dust Mite Allergy

By Erik Goldman

dust miteSublingual immunotherapy (SLIT) can reduce exacerbations of asthma associated with dust mite allergens, according to a recent study published in the Journal of the American Medical Association.

House dust mites are a common trigger of allergy-associated asthma, and up to 30% of all patients who are allergic to dust mites are non-responsive to inhaled corticosteroids, beta agonists, and other drug therapies.

SLIT, which involves daily sublingual exposure to highly dilute concentrations of an allergen, has proven effective in reducing the frequency and severity of allergic reactions to a number of common allergens. Until recently, however, it had not been tested in the context of dust mite asthma.

J. Christian Virchow and colleagues at the University of Rostock, Germany, explored the impact of SLIT in a cohort of 834 adults with confirmed dust mite-triggered asthma and related rhinitis, whose symptoms were not well controlled with inhaled corticosteroids.

The patients, seen at 109 centers across Europe, were randomized to once-daily treatment with a sublingual placebo (277 patients), or a low-dose (275 patients) or high-dose (282 patients) SLIT preparation of dust mite allergens. All were treated for a total of 6 months, and all were permitted to continue conventional drug therapies.

A total of 693 participants completed the full 6-month trial. Compared with the placebo group, both groups of SLIT patients showed small but significant reductiosn in moderate to severe asthma attacks over the 6 month period. 

Dr. Virchow estimated that the absolute reduction at 6 months was "9 or 10 percentage points," and there was no significant difference between the high and low-dose SLIT preparations (Virchow JC, et al. JAMA: 315 (6): 1715-25).

Though clearly not a definitive treatment for dust mite-related asthma, SLIT does represent a new adjunctive option for patients who are not getting substantial relief from conventional drug therapies. Virchow believes it is one well worth further exploration. He notes that, “among adults with house dust mite allergy–related asthma not well controlled by ICS, the addition of house dust mite SLIT to maintenance medications improved time to first moderate or severe asthma exacerbation during ICS reduction."

The authors acknowledge that the current study has limitations, among them the fact that the 6-month study period was significantly shorter than the typical durations of immunotherapy, which sometimes extend to 3 years.

Still, the fact that dust mite SLIT did produce measurable changes in clinical outcomes after only 6 months, suggests that this approach does have promise.

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