Meaning and Significance of “Alkalization Therapy for Cancer”

Wada, Hiromi; Hamaguchi, Reo; Narui, Ryoko; Morikawa, Hiromasa

doi:10.3389/fonc.2022.920843

Cited by 13 publications

(16 citation statements)

References 77 publications

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“…More research is needed on the mechanisms of the effectiveness of sodium bicarbonate and other buffer solutions in cancer patients. Alkalization (buffering) therapy does not conflict with standard treatment methods but can be used in combination to increase effectiveness ( 154 ).…”

Section: Tumor Acidity As a Target Of Treatmentmentioning

confidence: 99%

Tumor acidity: From hallmark of cancer to target of treatment

et al. 2022

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Tumor acidity is one of the cancer hallmarks and is associated with metabolic reprogramming and the use of glycolysis, which results in a high intracellular lactic acid concentration. Cancer cells avoid acid stress major by the activation and expression of proton and lactate transporters and exchangers and have an inverted pH gradient (extracellular and intracellular pHs are acid and alkaline, respectively). The shift in the tumor acid–base balance promotes proliferation, apoptosis avoidance, invasiveness, metastatic potential, aggressiveness, immune evasion, and treatment resistance. For example, weak-base chemotherapeutic agents may have a substantially reduced cellular uptake capacity due to “ion trapping”. Lactic acid negatively affects the functions of activated effector T cells, stimulates regulatory T cells, and promotes them to express programmed cell death receptor 1. On the other hand, the inversion of pH gradient could be a cancer weakness that will allow the development of new promising therapies, such as tumor-targeted pH-sensitive antibodies and pH-responsible nanoparticle conjugates with anticancer drugs. The regulation of tumor pH levels by pharmacological inhibition of pH-responsible proteins (monocarboxylate transporters, H+-ATPase, etc.) and lactate dehydrogenase A is also a promising anticancer strategy. Another idea is the oral or parenteral use of buffer systems, such as sodium bicarbonate, to neutralize tumor acidity. Buffering therapy does not counteract standard treatment methods and can be used in combination to increase effectiveness. However, the mechanisms of the anticancer effect of buffering therapy are still unclear, and more research is needed. We have attempted to summarize the basic knowledge about tumor acidity.

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Section: Tumor Acidity As a Target Of Treatmentmentioning

confidence: 99%

Tumor acidity: From hallmark of cancer to target of treatment

et al. 2022

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“…In a comparison of chemotherapy plus alkalization therapy versus chemotherapy alone in the treatment of advanced pancreatic cancer, the median OS was 15.4 (combination treatment group) vs. 10.8 months (chemotherapy alone group) ( p < 0.005) ( 9 ). Moreover, we previously found that patients with renal cancer, malignant lymphoma, gastric cancer, and breast cancer who were treated with alkalization therapy had favorable outcomes ( 10 ). As it remained unclear whether the combination of alkalization therapy with standard treatments would be as effective for HCC as for the cancers described above, we conducted a retrospective study of the effects of alkalization therapy on patients with HCC.…”

Section: Introductionmentioning

confidence: 99%

Effects of alkalization therapy on hepatocellular carcinoma: a retrospective study

et al. 2023

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BackgroundIn hepatocellular carcinoma (HCC) patients, is difficult to prevent recurrence even when remission is achieved. In addition, even with the advent of drugs that are effective for the treatment of HCC, a satisfactory extension of patient survival has not been achieved. To overcome this situation, we hypothesized that the combination of alkalization therapy with standard treatments will improve the prognosis of HCC. We here report the clinical results of HCC patients treated with alkalization therapy at our clinic.Patients and methodsPatients with HCC treated at Karasuma Wada Clinic (in Kyoto, Japan), from January 1, 2013, to December 31, 2020 were analyzed. Overall survival (OS) from both the time of diagnosis and the start of alkalization therapy for each patient was compared. The mean urine pH was also calculated as a surrogate marker of tumor microenvironment pH, and OS from the start of alkalization therapy was compared between patients with a mean urine pH of ≥ 7.0 and those with a mean urine pH of < 7.0.ResultsTwenty-three men and six women were included in the analysis, with a mean age at diagnosis of 64.1 years (range: 37–87 years). Seven of the 29 patients had extrahepatic metastases. Patients were divided into two groups according to their mean urine pH after the initiation of alkalization therapy: 12 of the 29 patients had a mean urine pH of ≥ 7.0, and 17 had a mean urine pH of < 7.0. The median OS from diagnosis was 95.6 months (95% confidence interval [CI] = 24.7-not reached), and from the start of alkalization therapy was 42.3 months (95% CI = 8.93-not reached). The median OS from the start of alkalization therapy in patients with a urine pH of ≥ 7.0 was not reached (n = 12, 95% CI = 3.0-not reached), which was significantly longer than that in patients with a pH of < 7.0 (15.4 months, n = 17, 95% CI = 5.8-not reached, p < 0.05).ConclusionsThe addition of alkalization therapy to standard therapies may be associated with more favorable outcomes in HCC patients with increased urine pH after alkalization therapy.

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“…In addition, our group has encountered patients with renal cancer, malignant lymphoma, gastric cancer, and breast cancer in whom alkalization therapy increased their urine pH, which may have been associated with their favorable outcomes. However, these are only case reports and require further investigation ( 56 ).…”

Section: Clinical Reports Of Alkalization Therapy For Cancermentioning

confidence: 99%

Clinical review of alkalization therapy in cancer treatment

et al. 2022

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One of the most unique characteristics of cancer metabolism is activated aerobic glycolysis, which is called the “Warburg effect”, and is a hallmark of cancer. An acidic tumor microenvironment (TME) resulting from activated anaerobic glycolysis is associated with cancer progression, multi-drug resistance, and immune escape. Several in vitro and in vivo studies reported that neutralization of the acidic TME by alkalizing agents, such as bicarbonate, resulted in the suppression of cancer progression and a potential benefit for anti-cancer drug responses. In clinical settings, alkalizing effects were achieved not only by alkalizing agents, but also by a following a particular diet. An epidemiological study demonstrated that more fruits and vegetables and less meat and dairy products are associated with an increase in urine pH, which may reflect the alkalizing effect on the body. However, it remains unclear whether alkaline dietary intervention improves the effects of cancer treatment. Moreover, there are few clinical reports to date regarding cancer treatments being performed on patients together with alkalization therapy. In this review, we investigated whether alkalization therapy, which includes an alkaline diet and/or alkalizing agents, improves cancer treatment.

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Meaning and Significance of “Alkalization Therapy for Cancer”

Cited by 13 publications

References 77 publications

Tumor acidity: From hallmark of cancer to target of treatment

Tumor acidity: From hallmark of cancer to target of treatment

Effects of alkalization therapy on hepatocellular carcinoma: a retrospective study

Clinical review of alkalization therapy in cancer treatment

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