Garlic – The Common Man’s Cure All

A recent study published in the Journal of Cancer Prevention Research by investigators in China compared the outcome of patients with lung cancer who consumed fresh garlic against those who did not. In the study of 1,424 lung cancer patients there was a 44 percent reduction of the risk of lung cancer for non-smokers.  Even among smoking patients the risk of lung cancer was reduced by 30 percent.

The findings of the study are consistent with a treatise that I published several years ago on garlic (Garlic: Medicinal Food or Nutritious Medicine? Robert A. Nagourney, Journal of Medicinal Food, 1998). In this study, I examined the history of garlic, as well as its chemistry and its medicinal properties. In addition to its anti-cancer properties, garlic is antibacterial, antiviral, antifungal, lowers blood pressure, reduces the risk of blood clots, lowers cholesterol and may serve as an anti-aging nutrient.

Where the recent study struck chord was its concordance with my strong recommendation from that 1998 article that we consume fresh garlic over the other preparations. The aged garlic extracts, dried garlic and garlic oil preparations lack the most important chemical constituent of all – allicin. Allicin, also known diallyl disulphide oxide (2-propanethiol sufinate) imparts the characteristic odor to garlic. It is only formed when the precursor alliin is enzymatically converted to the allicin via the action of the enzyme alliinase. Once allicin is exposed to excess heat or oxygen it undergoes a variety of conversions that lead to diallyl sulfone as well the diallyl di, tri, and tetra sulfides.

These compounds, though biologically active, do not carry the potency of allicin. It is for this reason that I have, over the past two decades, urged my patients, family and friends to consume fresh garlic as a foodstuff. Indeed as I write in my book, Outliving Cancer, our family consumes the equivalent 2 – 3 liters of fresh garlic a month.

The history of garlic as a medicinal is indeed rich. And it was Gallen, in 130 AD, who described it as “Theriacum rusticorum” (the common man’s cure all). I am pleased that two millennia later Chinese cancer researchers have provided additional data to support his prescient observation.

Neuroblastoma Response to Therapy Trumps Age

In April of 2013, we received a tissue sample from investigators in Victoria, Espirito Santo, Brazil. The pediatric oncologist involved requested assistance in the management of a four-year-old child with Stage IV (metastatic) neuroblastoma.

The patient was originally diagnosed in February with abdominal pain and a tumor. The tumor was identified by ultrasound as a large left-sided retroperitoneal mass. The patient was treated with the combination of doxorubicin plus cyclophosphamide. Within a month, it was evident that his “high risk neuroblastoma” would require stronger chemotherapy. Doses were adjusted upward and cisplatin was added. As the patient’s tumor infiltrated his bone marrow, his tolerance of chemotherapy became limited. By early June, after recovering from severe infectious complications, with no evidence of response to treatment, he was taken to surgery.

For background, neuroblastoma is the third most common malignancy of childhood. It arises from sympathetic ganglia (nerve cells) and presents in different forms. It has long been recognized that these tumors can be driven by an up-regulation of the oncogene MYCN. Children above the age of 1.5 years and those with wide dissemination are at highest risk.

We received this patient’s tissue and immediately isolated the malignant populations. As the tumor is only identified in children, it was a somewhat unusual occurrence for our laboratory. In addition, the patient had already received extremely aggressive treatment without benefit. We chose among the drugs that we considered potentially active for study and proceeded with our analysis.

The EVA-PCD assay results were highly instructive. First, those drugs that the patient had already received (platins, alkylating agents) were clearly inactive. Second, the signal transduction inhibitors like imatinib, and everolimus were also inactive. What was striking however, was the extraordinary degree of sensitivity to taxol that placed this patient among the most sensitive patients we have ever tested. The profile for taxol also extended to two taxol-based combinations: taxol plus platinum and taxol plus gemcitabine. However neither combination revealed significant synergy, suggesting that taxol was the principally active agent.

biology.arizona.edu

As I considered our laboratory findings in the context of the contemporary pediatric neuroblastoma literature, several interesting threads emerged. The first, was that investigators in Leiden, Netherlands had described a microtubule associated protein (MAP) encoded double cortin-like kinase gene (DCLK1) in neuroblastoma patients.  The second was the very early but promising work using aurora kinase inhibitors in this disease. It became evident that these observations had their nexus at microtubule function. In keeping with the adult literature this would clearly support classes of drugs that induce G2-M arrest in the cell cycle. I reasoned that the taxanes were highly appropriate for this child based both on our findings and these related molecular correlates.

We contacted the physician in Brazil, and recommended a taxol-based treatment program. It became evident that neither taxol, nor the related carboplatin plus taxol or taxol plus gemcitabine regimens, were in this pediatric oncologist’s lexicon for neuroblastoma. Our report included references to clinical trials in adult tumors where these combinations have been broadly applied. However, it was going to require a certain amount of creative thinking for this well-trained pediatric oncologist to cross walk our “adult” recommendations to this child in need. Fortunately, with the assistance from our collaborators in Sao Paolo, the physician agreed to use our combination in this child who was failing standard treatment.

The results were prompt and dramatic. Within a single cycle of therapy, virtually all symptoms resolved. The child began to eat well and gain weight and despite chemotherapy, the bone marrow function rapidly recovered and the blood counts normalized. With completion of two cycles, a repeat CT scan revealed complete resolution of measurable disease.

I have corresponded with the pediatric oncologist and expressed our delight with the outcome and of her willingness to work with us. This case represents not only a transnational collaboration (the subject of a recent ASCO presentation) but also the successful cross-fertilization between the pediatric and adult oncology specialties. We are deeply gratified on both accounts.

ASCO Update: Personalized Cancer Care – Our Contributions

As part of our ongoing blog postings we like to include recent presentations and publications. On July 9, I described our ASCO presentation exploring crizotinib, “Functional Profiling Leads to Identification of Accurate Genomic Findings.”

To conclude the review of our other presentations from that meeting, here is a brief summary of our work.

The first of the two was our international collaboration in personalized medicine for the treatment of advanced and drug-refractory cancers: “Clinical application of human tumor primary culture analyses.” The study reviewed the results of 67 patients from institutions across Brazil.

Tumor samples were transported by overnight courier to California for drug response profiling. A broad array of tumors were included. The overall success rate provided actionable results in 62 of 67 patients (92 percent). More than 75 percent of the studies provided results for between 8 and 16 drugs and combinations with a median of 12 reported. Several strikingly good responses were observed, including novel combinations identified in the laboratory. This study confirms the feasibility of international collaboration and reflects the globalization of medical care delivery.

The final study published by ASCO was also a collaborative effort with SageMedic of Larkspur, CA, The Ludwig Maximilians University Munich, Germany and the Weisenthal Cancer Group. The study was a meta-analyses that examined the sensitivity and specificity of human tumor primary culture studies and the efficacy of drug therapies selected, based on laboratory findings. In aggregate there were 28 retrospective and 15 prospective trials included.

The overall sensitivity was 0.92 (95 percent C.I. 0.89 – 0.95), and specificity of 0.72 (95 percent C.I. 0.67 – 0.77) with an area under the curve for the ROC of 0.893 (SE = 0.023, p < 0.001). When clinical outcomes were examined, it revealed a two-fold improvement for assay-guided therapy for standard of care (odds ratio 2.04, 95 percent C.I. 1.62 – 2.57, p <  0.001). Finally, the one-year survival rate for assay-guided therapy proved superior (OR 1.44, 95% C.I. 1.06 – 1.95, p= 0.02).

As can be seen from this well conducted meta-analysis, there is a wealth of evidence to support the use of human tumor primary cultures for the selection of chemotherapy.