, also known as Coriolus versicolor
or Polyporus versicolor
, has a long history of medical use in Asia, dating back hundreds of years in traditional Asian medicine. Tv
belongs to the more advanced Basidiomycetes class of fungi. It grows on tree trunks throughout the world in many diverse climates, including North America. The Tv
mushroom has a long history of treasured use in Asia as both a food and a medicine. In China, it is called yun zhi or cloud fungus. According to Kidd, the immunomodulatory activity of polysaccharide peptides in Tv
was discovered in 1965 in Japan by a chemical engineer who observed a case of cancer remission after ingesting yun zhi.2
Subsequent research led to identification of two closely related proteoglycan constituents of Tv
with anticancer activity: Krestin (PSK) and polysaccharide peptide (PSP). Krestin (PSK) has been studied most extensively and is in wide clinical use as an adjunctive and adjuvant cancer therapy in Japan and China.2,44,45
The closely related PSP was first isolated in China in 1983. Although some of the active constituents of Tv
have been studied, few data exist on the anticancer activity of the whole extract despite its common use in Asia and now in the United States.
There have been many peer-reviewed publications on the Tv
in cancer, including 37 in vitro articles, 55 animal studies, 43 published human clinical studies, and 11 review articles in gastrointestinal, breast, and lung cancer. In the last 2 years, five more Krestin (PSK) trials in colorectal cancer have been published,35,36,49
including one meta-analysis in 1,094 colorectal cancer patients,50
all showing a positive impact on clinical outcomes. Lindequist and colleagues and Hobbs have written excellent review articles on the pharmacologic potential of mushrooms, including Tv
is standard oncologic care in mainstream modern Japanese cancer management. Krestin (PSK) was approved in 1977 as a cancer therapy by the Japanese National Health Registry and represents 25% of the total national costs of cancer care in Japan.52
Oncologists in the West have only recently begun to turn their attention to immune-based therapies and, thus, have generally not noticed this potentially important therapy. Some of the clinical trial data from the east are of high quality. Several investigator teams at several high-quality cancer centers have replicated positive clinical findings. However, although the clinical data are strong, the immunologic rationale for proceeding with trials has never been fully articulated.
The rigorous clinical evaluation of PSPs extracted from the medicinal higher fungi Tv in well-designed trials conducted in the United States is not only justified but overdue. Clinical trials hi the United States are needed. But the logic of such trials needs to be built on sound immunologic mechanisms. To proceed with clinical trials in the United States, two requirements must be met. First, there must be enough high-quality clinical trial data from Japan and China that show clinical efficacy; second, there must be plausible immunologic mechanisms to justify proceeding with expensive prospective human trials.
Clinical trial data for Krestin (PSK) from China and PSP in Japan suggest that PSP immunomodulation improves disease-free and overall survival in breast cancer. In a randomized study of 158 esophageal cancer patients, the survival of the radiochemotherapy plus Krestin (PSK) (3,000 mg/d for 12 weeks) group was significantly better than that in the group receiving radiochemotherapy alone.53
Animal studies have shown that (β-glucan extracted from yeast enhances the antitumor effects of radiation (Gary Ostroff, 2007). It has been hypothesized that Tv
’s immunologic activity is the underlying mechanism responsible for its antitumor effects and its impact on survival rates.54
In the last 20 years, in vitro, animal, and human clinical studies have supported the use of commercially derived proteoglycans of Tv
in the treatment of stomach, colorectal, prostate, and breast adenocarcinomas.2,44
Two specific proteoglycans (Krestin (PSK)™ and PSP) have been extracted from Tv
and have been shown to have both anticancer and immunomodulatory activity in tissue culture, animal, and human studies. Of all of the medicinal mushrooms, Tv
has been studied the most thoroughly in terms of analysis of active constituents. There are preliminary data to support the hypothesis that Krestin (PSK), the most widely used of the Tv
derivatives, may be beneficial in the treatment of both estrogen receptor (ER)-positive and -negative breast cancers by mitigating the immunologic side effects of treatment and enhancing disease-free survival.40,41
Clinical trials of Krestin (PSK) in cancer began in the 1970s in Japan. Based on three decades of Asian clinical research, Krestin (PSK) as adjuvant therapy is indicated for cancers of the stomach, esophagus, nasopharynx, colon, rectum, lung, and breast.2,28,53–54
Most of the clinical research has focused on the effects of Tv
adjuvant therapy on disease-free survival and overall survival rates. In 1984, Sugimachi’s group at Kyushu University published an uncontrolled observational retrospective analysis of breast cancer patients with recurrent disease.55
Patients had received chemotherapy with and without Krestin (PSK) immunotherapy. The survival rate after recurrence was significantly extended by Krestin (PSK) immunotherapy.
In 1992, a large randomized trial with 914 women evaluated tamoxifen as an addition to the then-conventional chemotherapy.40
Randomized subgroups received Krestin (PSK) immune therapy (3,000 mg/d for 24 months) in addition to chemotherapy. Analysis revealed that Krestin (PSK) significantly extended survival in ER-negative, stage IIA patients without lymph node involvement. Morimoto and colleagues conducted a 5-year postoperative randomized controlled trial (RCT) comparing chemotherapy with Krestin (PSK) immune therapy in 376 women with stage II ER-negative breast cancer who received either a prodrug of 5-fluorouracil or 3,000 mg/d Krestin (PSK).41
The 5-year overall and relapse-free survival rates for ER-negative patients were the same regardless of whether they had received chemotherapy alone or Krestin (PSK) alone.
A third RCT conducted in Japan evaluated the efficacy of Krestin (PSK) as an adjunctive immune therapy in addition to combination chemotherapy in 227 operable breast cancer patients with vascular invasion in the tumor and/or metastatic lymph node involvement. Patients were randomized to receive chemotherapy of 5-fluorouracil, cyclophosphamide, mitomycin C, and prednisolone (FEMP) alone, FEMP + levamisole, or FEMP + Krestin (PSK). Krestin (PSK)™ was orally administered at 3,000 mg/d for 28 days. The 5- and 10-year survival curves for the FEMP + Krestin (PSK) group were superior to either FEMP alone or FEMP + levamisole. The authors concluded that immunotherapy using Krestin (PSK) improved the prognosis for breast cancer patients whose tumors showed histopathologic evidence of vascular invasion.