Acupuncture in Integrative Oncology

Full title: “Acupuncture and East Asian Medicine in Integrative Oncology”

ABSTRACT

Integrative medicine combines conventional Western medicine with complementary and alternative treatments. It is a practice that is informed by evidence to facilitate the body’s innate healing response. Integrative oncology allows precision in a therapeutic approach that is natural and less invasive. It emphasizes the therapeutic relationship between practitioner and patient and is an effective intervention in cancer treatments and patient care. Medicine is personalized when we account for genotype, patient preference, and expectancy. Acupuncture and herbal medicine have exemplified personalized medicine for over 3000 years, with the results supported by growing evidence in clinical findings with supporting symptoms like cancer pain, fatigue, and insomnia. East Asian medicine is a healing-oriented medicine, a lifestyle medicine that includes nutrition and diet, stress management, as well as a balance of mind-body-spirit. The nature of customization within acupuncture and East Asian herbal medicine is an ideal model for personalized patient care in integrative oncology. Through clinical findings, it shows promise to increase effectiveness of cancer care and promote health for cancer prevention.

CANCER AND WESTERN THERAPIES

Cancers are among the leading causes of death nationally and worldwide; their incidence is increasing as the population ages. They are also especially feared, because of their lethality, their symptoms, and the often toxic or disfiguring therapies used to treat them.¹

Research has showed that each cancer has its own genomic signature, with some tumor-specific features and some features common to multiple types.¹ Although cancers are largely a consequence of accumulating genomic damage during life, inherited genetic variations contribute to cancer risk, sometimes profoundly.¹ This new understanding of oncogenic mechanisms has begun to influence risk assessment, diagnostic categories, and therapeutic strategies, with increasing use of drugs and antibodies designed to counter the influence of specific molecular drivers.¹

Cancer is a complex disease that can have a wide range of properties, based on the specifics of the mutations that drive it, as well as epigenetic changes and changes to the local cellular environment of the tumor, often called the tumor microenvironment.² Progression of each individual cancer will differ, based on the types of changes and response of the body.² However, there are some common cellular features that can be generally observed during the onset and progression of cancer.² These features are referred to as the Hallmarks of Cancer.²

Surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy are examples of anti-cancer therapies currently being utilized for controlling tumor growth, prolonging survival time, and improving quality of life to some extent.³ Chemotherapy and radiotherapy are major postoperative adjunctive therapies or preferred therapies for patients with malignant tumors in middle and advanced stages, however, there are many side effects and complications such as myelosuppression, gastrointestinal tract reaction, cardiac damage, liver and renal function, or local radiation damage. Cancer cells have ability to develop resistance to these conventional therapeutics over time and some cancers are insensitive to these treatments and approach.³

Conventional therapies like chemotherapy and radiation target common cellular functions like DNA replication, cell division, and the DNA damage response.² Precision therapeutics, which can be small molecule drugs or biologics, are used to target a selected molecule based on the mutations in an individual’s cancer.²

As an example, small molecule drugs like erlotinib are for extracellular or intracellular targets.² Erlotinib interferes with the signaling pathway of cell proliferation.² Biologics like cetuximab are for extracellular targets.² Cetuximab is a monoclonal antibody therapeutic for colorectal cancer.² These precision therapeutics can be tailored to the patient’s needs on a cellular level to stem the progression of cancer. This level of precision finds common ground with acupuncture and East Asian medicine as each treatment is unique to each patient; no two patients with the same diagnosis will receive the same course of treatment.

There can be downsides to combination therapies; the risk of toxicity of the combined therapies is sometimes greater and more severe than that of the single therapy and the cost is higher, so it is important to be strategic about the design and evaluation of these types of therapies.² However, the upside can be enormous; well-designed combination therapies could allow us to target cancer cells more specifically, avoid or delay drug resistance, and improve patient outcomes.²

Receiving a cancer diagnosis and making decisions about treatment can cause stress.³ Cancer can cause a long list of signs and symptoms, including fatigue and pain.³ Conventional treatments for cancer, including surgery, chemotherapy and radiation, also can cause fatigue, pain and stress, as well as nausea, diarrhea or constipation, weight loss and other complications.³ Some of these complications linger after treatment has ended.³

ACUPUNCTURE

The practice of integrative oncology can help relieve these side effects and improve treatment outcomes.³ Different mechanisms of acupuncture have been proposed to explain its efficacy, including theories of the neural system, endocrine cytokine or immunological regulation, its eventual role has become one of treatment support to alleviate the side effects and prevent re-occurrence.⁴

More than 3000 years ago in the Yin and Zhou era, the name of “tumor” (“瘤” liu) has been recorded on the oracle bone inscriptions of that period. The Neijing (Huang Di Nei Jing) also discusses the etiology and pathogenesis of tumors, and believes that the formation of tumors is related to weakness of righteous qi (正气 zhèngqì), invasion of external evils (pathogens), and internal injuries of seven emotions. Lingshu – Nine Needles says: “The eight winds in four seasons become a guest (blockage) in the meridian, and so is the tumor (瘤 liu).” It is believed that the invasion of external evils can cause tumors. In ancient text, acupuncture points were defined as the visceral reaction points on the body surface where the qi of the organs and meridians are transfused.⁴ Triggering these acupuncture points promotes the flow of qi and blood and regulates organ function.⁴ In the last half of the 20^th century, many studies conducted on animals and humans, according to Moritaka, et al., (2010), have demonstrated multiple biological responses related to acupuncture, including neural regulation, endocrine regulation, and immunological regulation.⁴ Studies have shown that endocrine regulation alleviates cancer pain and immune regulation can promote recovery of immune function in cancer patients.⁴

The precise nature of acupuncture treatments is represented in “Effectiveness of auricular acupuncture in the treatment of cancer pain: randomized clinical trial.” In this 2018 study, the approach was found to be effective in reducing the pain intensity of cancer patients receiving chemotherapy.⁵ In addition, it was associated with reduction in the consumption of analgesics.⁵ The main mechanism of the analgesic effect of acupuncture may be related to its effect in decreased substance P and upregulating plasma b‑endorphin levels.⁵ The technique was shown to be safe, effective, inexpensive and with minimal risk to patients.⁵ The acupuncture points used were Shenmen, Kidney, Sympathetic, Muscle Relaxation and the energy balance points, defined through the Five-Elements theory.⁵ According to the study, the energy balance points were defined individually and corresponded to the organ and the viscera that represent the element in which the patient’s imbalance begins.⁵ From this, the acupuncture points of the Five-Element cycle (wood, fire, earth, metal, water) are used to restore the harmony and health of the individual.⁵ This approach of diagnosing and treating each patient in a tailored way is foundational to the practice of acupuncture.

The effectiveness of acupuncture has been compared with cognitive–behavioral therapy (CBT-I) for insomnia (CBT-I) in cancer survivors. In “Acupuncture versus cognitive behavioral therapy for insomnia in cancer survivors: A randomized clinical trial,” the findings show clinically meaningful reduction in the severity of insomnia, an improvement that was sustained for up to 20 weeks in each treatment.⁶ It was also found that acupuncture reduced pain severity more than CBT-I in “The management of cancer-related fatigue after chemotherapy with acupuncture and acupressure: A randomised controlled trial.”⁷

A methodologically feasible RCT compared acupuncture, acupressure, and sham acupressure in post‑chemotherapy fatigue patients and found positive results in enhancing patients’ general fatigue (P < 0.001), physical fatigue (P = 0.016), activity (P = 0.004), and motivation (P = 0.024).⁷ A single‑arm, phase II pilot study showed clinically meaningful results in improving post‑chemotherapy fatigue with acupuncture.⁸ On the other hand, insomnia may lead to fatigue and depression, which are also commonly observed in cancer patients.⁴ A recent RCT, “Clinical research of acupuncture on malignant tumor patients for improving depression and sleep quality,” evaluated 80 patients and revealed acupuncture can effectively reduce malignant‑related depression and improve the sleep quality of cancer patients.⁹

EAST ASIAN MEDICINE

There are numerous research studies focused on the therapeutic effect of natural antioxidants in medicinal plants. The herbs derived from these plants have a wide range of biological effects, including anti-cancer, anti-inflammatory, anti-aging, and anti-atherosclerosis.¹⁰ Spiridon et al. and Husein et al. reported that phenolic content from extracts of a number of herbal plants (like Origanum vulgare L. and Melissa officinalis) showed positive correlation with its antioxidant activity.^11,12 Free radicals pose a threat of damaging DNA, proteins, and cellular membranes, leading to onset and progress of cancer.¹³ Therefore, antioxidants can play a role in neutralizing abnormal cancer cell division and DNA damage.¹⁴

In “Hedyotis diffusa Willd extract suppresses Sonic hedgehog signaling leading to the inhibition of colorectal cancer angiogenesis” that Bai Hua She She Cao (Herba Hedyotis Diffusae) could suppress tumor angiogenesis in vivo via inhibition of SHH signaling in colorectal cancer as it decreased the expression of key meditations in the SHH pathway.¹⁵ In “The effect-enhancing and toxicity-reducing action of the extract of herb Scutellariae barbatae for chemotherapy in hepatoma H22 tumor-bearing mice,” Ban Zhi Lian (Herba Scutellariae Barbatae) could promote the tumor inhibition rate of 5-fluorouracil, which is often prescribed to pancreatic cancer patients.¹⁶ Cryptotanshinone, one of the constituents of Dan Shen (Radix Salviae Miltiorrhizae) could exert anti-cancer effects by inducing apoptosis and cell cycle arrest via inhibition of the STAT3 signaling pathway in human pancreatic cell line in the study.¹⁷ This anti-cancer effect was studied in “Cryptotanshinone suppresses the proliferation and induces the apoptosis of pancreatic cancer cells via the STAT3 signaling pathway.” From “First-in-human phase II trial of the botanical formulation PHY906 with capecitabine as second-line therapy in patients with advanced pancreatic cancer,” it is noteworthy that the common herb, Huang Qin (Radix Scutellariae), is one of the major herbs of a Chinese herbal formula PHY906, which has been shown to be a safe and feasible salvage therapy for advanced pancreatic cancer in a phase II clinical trial.¹⁸

Patients with cancer often experience sleep disturbance. Wei Gui Pi Tang may show a potential benefit for improving sleep disturbance with mild adverse effects.¹⁹ Jia Wei Gui Pi Tang was originally prescribed for insomnia with Heart and Spleen deficiency, and then generally prescribed for all types of chronic insomnia.¹⁹ Currently, Jia Wei Gui Pi Tang is the most common herbal formula prescribed for sleep disturbance in East Asia.²⁰ According to the 2010 study “Potentiating effect of spinosin, a C-glycoside flavonoid of Semen Ziziphi spinosae, on pentobarbital-induced sleep may be related to postsynaptic 5-HT(1A) receptors,” it was found that one of active components in Jia Wei Gui Pi Tang—spinosin from the herb Da Zao (Ziziphus jujube)—has a sedative-hypnotic effect, especially on REM sleep via the serotonergic 5-HT receptor.^21,22 A formula could be modified if the patient has additional symptoms like nausea, diarrhea, and constipation, which are all common side effects of chemotherapy treatment.

CONCLUSION

Acupuncture and East Asian medicine are potential interventions to optimize the effectiveness in cancer patient care. We are at the tip of the iceberg of integrative oncology. The intervention encourages and supports the next generation of scientists to develop creative new approaches for detecting, measuring, and analyzing a wide range of biomedical information— including molecular, genomic, cellular, clinical, behavioral, psychological, physiological, and environmental parameters. This can provide us the early insight into pharmacogenomics, enabling the provision of the right treatment, right care, to the right patient. Knowing the etiology of cancer, we may now take a step forward to prevent and reduce the risk of the disease. As a lifestyle medicine, acupuncture and East Asian medicine is an excellent avenue to manage stress, improve nutrition and diet, and overall adopt a healthier lifestyle.

References

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