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.
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).
They 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.'" 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.