The first osteopathic tenet describes the human body as a unit and considers a patient's mind, body, and spirit throughout care. The idea that the body is a unit is vital for providing care to patients with cancer. Physicians must acknowledge that cancer can have effects beyond physical manifestation, including emotional and spiritual ramifications. Furthermore, it is common to describe people with cancer as “warriors” who “battle” cancer, but using this language can make people feel as though they are quitting or giving up if they decide not to take futile toxic chemotherapy in the setting of advanced incurable disease.³ Part of our job as physicians is to remember that a disease cannot be “fought” at the expense of the patient. 

Through the tradition of Still, osteopathic manipulative medicine is used to promote self-healing. For example, osteopathic manipulative treatment techniques that target the immune system have shown that the body has the inherent capacity for self-healing.¹ The principle of self-healing is still applied when considering the biological basis of cancer and the role of the individual patient's immune system. In cancer research and therapy, the pendulum is moving away from cytotoxic chemotherapeutics and toward harnessing the power of the immune system. For example, immune-based therapy has shown promise in numerous malignant tumors, including melanoma, non–small cell lung cancer, renal cell carcinoma, hepatocellular carcinoma, and solid tumors with high microsatellite instability (MSI-high).^4-6 

Although there has been success in treating patients with immunotherapy, most patients do not respond to this treatment.^7,8 However, researchers are starting to unravel the mechanisms behind this resistance to immunotherapy. For example, patients with metastatic melanoma who were nonresponders to ipilimumab, an anticytotoxic T-lymphocyte antigen protein 4 antibody, were found to have tumors with genomic defects in the interferon γ pathway.³ Thus, an alteration in the structural framework of the interferon γ pathway led to a loss of drug function. In cancer research, structural changes in key biological pathways have been shown to have a beneficial effect on cellular function and adversely affect therapeutic intervention.^14,15 

The osteopathic tenet that structure and function are reciprocally related is best illustrated in the evolving knowledge of cancer biology and our understanding that cell and molecular biology governs function. The advanced genomic editing system CRISPR/Cas9 has revolutionized the way scientists can manipulate DNA. The bacterially derived CRISPR/Cas9 system is composed of a nuclease protein, Cas9, which cuts double-stranded DNA along with a guide RNA molecule that directs Cas9 to a specific DNA sequence.^9-13 The CRISPR/Cas9 system highlights how specific genetic mutations alter a malignant phenotype and allows for expeditious preclinical modeling of specific targeted therapies, thus helping researchers continue to discover how underlying molecular structural alterations can influence outcomes. 

The structure and function relationship is further demonstrated in a tumor's mutational status. In colorectal cancer, mutational analysis, including tests for KRAS, NRAS, and BRAF mutations and MSI-high tumors, has enabled personalized therapy beyond standard TNM staging–based therapy.¹⁴ Researchers are able to tailor treatments to maximize efficacy as the understanding of both somatic and germline mutations improves. For example, patients with resected colorectal liver metastasis harboring a KRAS mutation were found to have a significantly worse 3-year recurrence-free survival after adjuvant hepatic artery infusion plus systemic therapy than patients with KRAS wild-type mutations.¹⁵ Additionally, the epidermal growth factor receptor, or EGFR, antagonist cetuximab has been shown to provide no survival advantage in patients with a KRAS mutation.¹⁶ On the other hand, patients with solid organ MSI-high tumors have shown a greater response to immune checkpoint inhibitors, specifically nivolumab.¹⁷ Therefore, by understanding the differences in tumor mutational status, therapies can be directed toward the individual patient rather than the disease. This approach can save patients from unnecessary procedures and therapies, which all carry risk. Furthermore, as researchers and physicians better understand a patient's genetic structure, treatment can be tailored to fit a genetic phenotype. For example, a germline BRCA mutation is known to confer a high risk of breast as well as ovarian cancer in woman. As the genetic structure of BRCA is altered, there is a loss of function of tumor suppression, leading to an increased risk of cancer. As a result, prophylactic surgery is routinely recommended to decrease the risk of cancer.^18,19 

As scientists make advances in the basic understanding of cancer biology, this knowledge must be translated to the bedside. Cady²⁰ highlighted the importance of understanding tumor biology and its role in the development of a rational treatment strategy, whereby patients with cancer undergo an operation for their disease, but without proper selection, aggressive biological processes will override even the most technically sound procedure or advanced targeted or immune-based therapy.²⁰ 

The principle of rational therapy is exemplified in pancreatic adenocarcinoma, where patient outcomes have not improved despite increased understanding of the complexities of both genetics and epigenetics and the interplay of the tumor cells, the stroma, and the immune system.^21,22 Pancreaticoduodenectomy is the lone option to achieve long-term survival, but it is not without associated high postoperative morbidity. Additionally, even with the most technically sound procedures, most patients will have recurrence, often in the form of liver metastasis.²³ Preclinical data have shown that pancreatic cancer metastasis often occurs early in the course of disease, making resection a fruitless endeavor.²⁴ Therefore, one may argue that patients with potentially resectable pancreatic cancer should receive upfront neoadjuvant chemotherapy to address micrometastatic disease. Patients who receive neoadjuvant chemotherapy are more likely to complete the treatment regimen, and neoadjuvant therapy allows for a window of time to test for unfavorable tumor biology.^25,26 Patients at risk for metastatic disease could therefore avoid the morbidity of an operation that would be of no therapeutic benefit. 

The climate of cancer research encompasses much of the osteopathic philosophy. Scientific advances leading to a more in-depth understanding of tumor biology have led to novel treatments to battle cancer, allowed for a more personalized approach to cancer care, and rebelled against the “one-size-fits-all” model. In managing a disease that truly affects the person as a whole, physicians must remember Still's maxim: “To find health should be the object of the doctor. Anyone can find disease.”²⁷