With its ability to target the abnormal metabolism of cancer cells, Sodium dichloroacetate (DCA) has shown promise in recent years of research as a metabolic cancer therapy. Its clinical value and safety in treating cancer, particularly certain forms like medullary thyroid carcinoma, have shown promise and positive effects in many cancer patients.
Here we would like to discuss the case report of a 51-year-old male suffering from terminal medullary thyroid carcinoma (MTC). Multiple episodes of chemotherapy and other treatments did not cure him of the disease, and on the contrary, he was left with advanced disease along with multiple site metastases. Then he discovered a promising drug called Sodium dichloroacetate, or DCA for short. The response to this simple, old medicine was remarkable, and he became disease-free with virtually none to minimal side effects
Before we delve into the story of this fateful patient, let’s briefly discuss medullary thyroid cancer and DCA.
Table of Contents:
• Understanding Medullary Thyroid Carcinoma
• What Progress Has Been Made with DCA Treatment for Cancer?
• A Remarkable Journey with DCA in Treating Metastatic Medullary Thyroid Cancer: The Case Study
Understanding Medullary Thyroid Carcinoma: Origins, Symptoms, and Genetic Factors
Medullary thyroid carcinoma is not a very common thyroid malignancy, but it is a rare type of thyroid carcinoma, accounting for approximately 4% of thyroid carcinoma. Contrary to this, papillary thyroid carcinoma (PTC) is the one that tops the list of thyroid carcinomas.
Papillary thyroid carcinoma takes its origin from the thyroglobulin-producing follicular cells, whereas calcitonin-producing parafollicular cells (C-cells) are the originator cells for medullary thyroid carcinoma. Thyroglobulin is a protein, and calcitonin is a hormone.
People with MTC present with symptoms like flushing, diarrhoea, and weight loss, which can be attributed to high levels of serum calcitonin secreted from these tumors.
Calcitonin levels can be used to monitor the course of therapy and assess MTC response to treatment, provided the calcitonin levels are elevated before starting the treatment or at the time of diagnosis.
Although MTC is often sporadic, it can also appear in conjunction with multigenerational family history and is, in 25 % of cases, caused by hereditary factors. The genetic basis is polyallelic autosomal dominant germline mutation in the RET proto-oncogene (coding for membrane receptor protein tyrosine kinase) whose manifestations are related to multigene syndromes: MEN2A or MEN2B. (ref)
Treatment Approaches for Medullary Thyroid Cancer: Surgery and Challenges with Advanced Disease
The treatment of choice for medullary thyroid cancer remains surgery, specifically total thyroidectomy. However, this treatment approach is only feasible if the patient is diagnosed while the thyroid cancer is still in its early stages.
There is still hope for patients with locally advanced or metastatic disease, as total thyroidectomy with lymph node dissection is usually recommended. Once metastases develop, these tumors are typically unresectable, but it is still possible to treat the disease and achieve remission.
Advanced endocrine malignancy treatment options are often unsatisfactory and are associated with poor patient prognosis. Recommended therapies, like cytotoxic chemotherapy and radiation therapy, are associated with possible significant toxicity. These treatments have been reported to have limited efficacy and excessive side effects. (ref)
Sodium Dichloroacetate (DCA): A Promising Therapeutic Agent in Cancer Treatment and Metabolic Targeting
Dichloroacetate (DCA) is a small molecule (150 Da) with high bioavailability. This allows it to reach areas like the brain that standard drugs can’t typically access. (ref.)
The mechanism of action for this effective anti-cancer strategy is the inhibition of the aerobic glycolysis pathway (the usual route for energy production in cancer cells) by suppressing the mitochondrial enzyme pyruvate dehydrogenase kinase (Warburg effect).
The good news is that cancer cells cannot shift to glucose oxidation when glycolysis is inhibited, so DCA-treated cancer cells will be short of their cellular energy supply (ATP). DCA prevents cancer cells from fuelling themselves by blocking their intake of the enormous amount of sugar they use to produce energy.
At lower doses, DCA stops tumor growth and progression and halts metastasis (static action).
At higher doses, DCA not only halts tumor growth but also begins shrinking them (cidal action), eventually offering hope of complete eradication. The chances grow even higher when DCA is combined with other treatments. Higher DCA dosage levels can be combined with naturopathic products to minimize potential reversible side effects on peripheral nerves. (ref.)
According to Bonnet et al.’s research, the old, time-tested drug Sodium Dichloroacetate (DCA) can reverse the Warburg phenotype in cancer cells both in laboratory tests and human beings, leading to natural cancer cell death and tumor shrinkage. Previously, it was believed that this was impossible, as the mitochondria in malignant cells were thought to be permanently altered and unable to trigger apoptosis. (ref.)
The anti-cancer mechanisms of DCA include inhibiting angiogenesis, increasing apoptosis, decreasing mitosis, activating the immune system, and targeting cancer stem cells. Seyfried (USA), whose work on this drug was published in 2011, highlighted the importance of inhibiting these cancer-promoting processes and suggested that a multi-energetic, targeted approach is superior to traditional treatment methods alone. (ref.)
Establishing the Safety of DCA
In 2006, researchers sought to establish the safety profile of DCA use in humans, examining both adults and children. (ref.1, ref.2) To our surprise it was found to be a comparatively safe drug, with no hematologic, cardiac, pulmonary, or renal toxicity. The main side effects that have been established are those exhibiting in our nervous system (peripheral neuropathy), and the good news: they are reversible upon discontinuation and entirely preventable by adhering to the protocol and taking neuroprotective supplements. (ref.)
DCA’s Cancer-Fighting Potential Unveiled
In January 2007, based on a landmark paper, it was established that DCA is highly efficacious in treating human breast, lung, and brain cancers in vitro and in vivo (experimental rodents).
DCA research has continued, and it has been shown to have in vitro efficacy against multiple human cancer cell lines, including ovarian (ref.), neuroblastoma (ref.), and colon.
In 2008, Cao et al established symbiotic relationship with radiotherapy in prostate cancer cell lines. The increased levels of BCL-2-associated X protein led to a higher rate of cancer cell death. (ref.)
Medicor Study Reveals Positive DCA Outcomes in Diverse Cancer Patients
In 2009 an observational data analysis of therapy with DCA was done at Medicor Cancer Centres on 347 patients. Patients’ ages ranging from 2 years to 90 years were considered under this trial. Variety of primary cancers were treated with DCA. The researchers were able to evaluate 179 of the total patients. The rest of the patient data could not be evaluated because of various reasons.
106 (60%) patients showed a positive response to DCA. Out of which 21 patients (12%) showed complete remission/decrease in tumor size. 2 patients (1%) had complete remission of metastatic cancer. The other 19 patients (11%) had measurable tumor reduction. Rest of the patients showed decreased tumour marker levels/Hematologic profile improvement/Absence of progression of disease. (ref.)
DCA: A Versatile Tool in Cancer Treatment
A research study published in 2010 by Michelakis et al. gave us an insight into the reversibility of cancer-specific metabolic and mitochondrial remodelling in glioblastoma. 49 patients showed mitochondrial hyperpolarization, which was rapidly reversed by DCA.
The study confirmed that DCA works for cancer by reactivating the mitochondria in cancer cells, shifting their metabolism from glycolysis to oxidative phosphorylation, which promotes natural programmed cancer cell suicide and inhibits tumor growth. (ref.)
DCA works by depolarizing mitochondria, increasing reactive oxygen species, and inducing apoptosis in cancer fast-dividing and stem cells. It also inhibits hypoxia-inducible factor-1α, activates p53, and suppresses angiogenesis both in lab and animal studies. (ref.)
Investigation into DCA efficacy in treating various cancer lines continued since then. DCA showed efficacy in treating multiple human cancer lines. Various researchers proved the efficacy of DCA in vivo in various cancer lines ovarian (ref.), neuroblastoma (ref.), colon (ref.), lung carcinoid (ref.), cervical (ref.) and endometrial (ref.), bile duct/ cholangiocarcinoma (ref.), bladder (ref.), gastric (ref.), head and neck squamous cell carcinoma (ref.), B-chronic lymphocytic leukaemia (ref.), hepatocellular carcinoma (ref.), Non-Hodgkin’s follicular lymphoma (NHL) (ref.), radioresistant medulloblastoma (ref.), melanoma (ref.), multiple myeloma (ref.), pancreatic adenocarcinoma (ref.), pancreatic neuroendocrine carcinoma (ref.), prostate carcinoma (ref.), renal cell carcinoma (ref.), osteosarcoma (ref.), angiosarcoma (ref.), rhabdomyosarcoma (ref.), fibrosarcoma (ref.), thyroid carcinoma (ref.), uterine (endometrial carcinoma) (ref.), cervical carcinoma (ref.) and Wilm’s tumor. (ref.)
DCA: Effective Alone or Combined in Cancer Treatment
A study illustrating the symbiotic relationship between DCA and radiotherapy (in vitro) was published in 2012 in patients with a metastatic renal squamous cell carcinoma. (ref.) In 2012 a case of cholangiocarcinoma was successfully treated with a combination of drugs like omeprazole and tamoxifen. (ref.)
Still DCA is not a prescribed drug by NCCN or any other prominent oncology forums; it has been used as an off-label drug by doctors for patients who have exhausted nearly all methods of conventional therapies.
The vast ongoing research and clinical experience show that DCA can be used by itself, with alternative medicines, or along with conventional treatments such as chemotherapy, radiotherapy, targeted therapy, immunotherapy or surgery.
Case Report: Transformative Cancer Healing Journey with DCA for Terminal Thyroid Cancer
The ill-fated story of this 50-year-old gentleman began in 2001, when he was diagnosed with medullary carcinoma thyroid with lymph node involvement. It was a sporadic form of cancer with no genetic factors. His twin brother was cancer-free. His elevated calcitonin levels were successfully treated with a chemotherapy regimen that included dimethyl triazenoimidazole carboximide (DTIC) and 5-fluorouracil.
In 2004, he was again diagnosed with a recurrent disease and was treated with an alternative chemotherapy consisting of a combination of drugs, including carboplatin and daunoxome. However, calcitonin levels were still elevated. He started treatment with Sandostatin (a somatostatin analogue) and a combination of etoposide and carboplatin to lower his calcitonin levels, which were initially 13,280 pg/ml. However, instead of decreasing, his calcitonin levels rose to 20,074 pg/ml.
In 2005, he was treated with a different chemotherapeutic drug protocol (carboplatin, Iressa, Sandostatin, and Zometa), but no success was achieved, and he continued to have elevated calcitonin levels. Additionally, he developed bone metastasis and was prescribed Samarium-153 to help manage his bone pain.
In 2006, chemotherapy of mitomycin C and cisplatin was administered, while he continued Tarceva and Sandostatin. The calcitonin levels remained elevated.
The 2008 year brought more bad news for this patient in the form of multiple metastases in the thoracic area and mediastinum, as confirmed in PET studies. The calcitonin levels kept on increasing, manifesting as diarrhea.
The patient was ineligible for any newer therapies, like the new tyrosine kinase inhibitor under a clinical trial and was confirmed to have a very poor prognosis.
In December 2008, out of despair, he started a protocol of 10 mg/kg of DCA with 750 mg of thiamine supplement. Thiamine was added to prevent reversible peripheral neuropathy, which is one of the possible side effects. Changes in right lumbar metastases and in pelvic area were remarkable compared to PET/CT in October 2008. A small shadow indicating a remaining tumor was observed at the T4 level, which is consistent with the primary tumor metastasis seen on the initial 2008 PET scan.
Table – Milestones of the treatment and follow up
| Date | Treatment | Calcitonin level (<20pg/ml) | PET Scan finding |
| 2001 | Surgery/ DTIC & 5-fluorouracil | Elevated | MTC with lymph node metastasis |
| Early 2004 | Carboplatin and Daunoxome | 13,280 | |
| Later 2004 | Sandostatin (carbo-Iressasomatostatin) & etoposide plus carboplatin | 20,074 | |
| 2005 | Carboplatin, Iressa, Sandostatin and Zometa, samarian-153 for pain | Remain elevated | |
| 2006 | Mitomycin C and cisplatin were administered, while he continued on Tarceva and Sandostatin. | Remain elevated | |
| October 2008 | 25,843 | Multiple new metastatic sites in the bones and other regions – thoracic area, mediastinum, thoracic T4, lumbar 3, 4, & 5, os ilium, dorsal para-iliosacral region, os acetabulum, ascending ischium, retroclavicular areas, behind sternocleidomastoid. | |
| December 1, 2008 | 10 mg/kg dichloroacetate (DCA) + 750 mg capsule of Thiamin | 38,611 | |
| February 2009 | Continued the DCA protocol | 8,655 | |
| May 2009 | Continued the DCA protocol | 2,000 | Overall reduction in tumor numbers and sizes in the lumbar, and pelvic areas followed by the thoracic area. The lymph node metastases were very small compared to the previous PET. Central necrosis had increased in the mediastinal tumor. |
In February 2009, a decrease in the thyroid tumor marker calcitonin to 8,655 pg/ml was first noted (norm is less than 20 pg/ml). A further reduction in calcitonin to 2,000 pg/ml was observed two months later.
In May 2009, after 5 months of DCA administration, the PET scan showed a noteworthy reduction in tumor numbers and sizes.
This above-mentioned success story in treating MTC with DCA gives a new silver line for these patients. DCA has shown a significant impact in treating metastatic medullary thyroid cancer, highlighting its promise for future cases. More studies on other MTC patients are needed to reveal valuable insights on how to incorporate DCA in similar situations, especially for those who have exhausted conventional chemotherapy options.
In other words, despite being a generic compound, DCA has all the hallmarks of a wonder drug for those uncommon and often treatment-resistant cancers. It is less toxic, much cheaper, and readily available.
Could this be the next big breakthrough in a disease that has so far resisted all our best efforts?
Medullary thyroid carcinoma relapse reversed with dichloroacetate: A case report
References
1. Flavin, D. (2010 Sep; 1(5)). Medullary thyroid carcinoma relapse reversed with dichloroacetate: A case report. Oncol Lett, 889–891
2. Michelakis, E. D., Webster, L., & Mackey, J. R. (2013 Aug). Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. British Journal of Cancer, 108(3): 490–495
3. Stockwin, L. H., Yu, S. X., Borgel, S., Hancock, C., Wolfe, T. L., Phillips, L. R., et al. (2010). Sodium dichloroacetate (DCA) selectively targets cells with defects in the mitochondrial ETC. British Journal of Cancer, 102: 1251–1258
4. Maia AL, Siqueira DR, Kulcsar MA, Tincani AJ, Mazeto GM, Maciel LM. (2014 Oct). Diagnosis, treatment, and follow-up of medullary thyroid carcinoma: recommendations by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism. Arq Bras Endocrinol Metabol, 58(7):667-700