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.
The consensus on the prevention and correction of hyperglycemia in patients with HR+ HER2- metastatic breast cancer treated with alpelisib was developed by the experts of the Russian Association of Endocrinologists and the Russian Society of Clinical Oncology. The consensus contains recommendation on risk assessment, prophylaxis and correction of hyperglycemia regarding the baseline metabolic status of the patients.
Aim. The aim of the study is to examine the efficacy and safety of eribulin in HER2-negative metastatic breast cancer (BC) in Russian clinical practice. Materials and methods. The analysis included 459 patients with advanced BC from 44 federal and municipal medical clinics in Russia and received at least 2 courses of treatment with eribulin in accordance with the registered indications for drug. The average age of women was 56 years (between 29 and 81 years), 83% of patients had HER2-negative tumor subtype (49.9% - luminal BC and 33.1% - triple-negative BC) HER2-positive biological tumor subtype was registered in 17% of patients. Visceral metastases were diagnosed in 73% of patients and three-zone and multiple zone metastases were diagnosed in 41.6% of cases. The median number of prior lines of therapy in patients with disseminated disease was 2; anthracycline and taxane chemotherapy was applied in 94.3% of patients, and 38.1% of patients were recived CT plus capecitabine. Standard treatment regimen with eribulin was cotinuing (1.4 mg/m² as a 2-5-minute intravenous infusion administrated on days 1, 8 of a 21-day cycle) until disease progression, unacceptable toxic effects, or impossibility of the drug administration for any other reason. We estimated the efficacy and safety of treatment with eribulin in Russian patients with HER2-negative BC. Results. Objective response rate was achieved in 20.5% of cases, complete response rate was in 3.2%, partial - 17.3%, and the stable disease rate was marked in 52.7% of women, and in 19.7% of these cases was prolonged more than 6 months. The frequency of objective response was higher in luminal BC group compared with triple-negative BC: 23.5% vs 15.8%; tumor growth control 76.9% vs. 67.8%, respectively; p
Locally advanced gastric cancer (GC) is often managed by neoadjuvant chemotherapy and surgery; however, pathological complete responses to preoperative systemic treatment are rare. Some GCs are characterised by high-level microsatellite instability (MSI-H) and therefore are potentially sensitive to anti-PD1 (the programmed death 1) therapy. Neoadjuvant immune checkpoint blockade demonstrated promising results in a number of trials involving various categories of patients with cancer; therefore, we considered feasible to offer preoperative nivolumab to a patient with T3N1M0 MSI-H GC. The patient experienced a reduction of the tumour size and the analysis of surgical material revealed complete elimination of tumour cells. MSI-H status deserves to be considered in future trials on patients with GC.
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