Greater Appeal and Greater Harm? Young Adults' Preference for Menthol Versus Nonmenthol Very-Low-Nicotine Cigarettes in a Cross-Over Trial.

Cancer is a major public health concern that threatens human health. According to the International Agency for Research on Cancer (IARC), there were 19.976 million new cancer cases and 9.7 million cancer-related deaths worldwide in 2022. Cancer pain, particularly in the advanced stages, is characterized by prolonged, persistent, and often intractable pain, which severely affects the survival quality of patients., According to the World Health Organization’s (WHO) three-step approach to analgesia, the management of cancer pain is typically categorized into three stages, progressively increasing the intensity of treatment from non-opioids (eg, NSAIDs) to weak opioids (eg, tramadol) to strong opioids (eg, morphine) Clinical studies have shown that 92% of patients receiving the full WHO three-step therapy eventually required conversion to strong opioids due to inadequate pain relief Current clinical pain management for patients with advanced cancer, primarily relying on opioids, can alleviate pain but is associated with adverse effects, such as nausea, vomiting, dizziness, and respiratory depression. The long-term or excessive use of opioids may lead to dependency and addiction, limiting their clinical utility., Experimental and observational studies suggest that opioids may promote tumor growth and increase infection risk via the hypothalamic–pituitary–adrenal axis, potentially reduce the efficacy of immunotherapy, and even shorten patient survival. Moreover, the severity of cancer-related pain and the corresponding opioid requirements have been associated with lower survival rates in patients with advanced cancer., Therefore, there is an urgent need for novel therapeutic approaches to alleviate cancer pain, without the adverse effects of traditional analgesics. The Warburg effect hypothesis, proposed by Nobel laureate Otto Warburg in 1927, which posits that tumor cells preferentially utilize glycolysis for energy production, even in the presence of oxygen, and that the proliferation of cancer cells can be effectively inhibited by restricting or modifying the uptake of glucose. A metabolism-based anticancer strategy has been developed to regulate glucose metabolism through insulin-induced hypoglycemia combined with low-dose anticancer treatment. Because this therapeutic regimen was designed based on principles related to tumor metabolic vulnerability and the Warburg effect hypothesis, the term “Warburg therapy” is used throughout this manuscript for descriptive convenience rather than as a standardized therapeutic category. During the administration of Warburg therapy, insulin will be utilized to induce short-term hypoglycemic states in patients and combined with low-dose chemotherapeutic agents to inhibit tumor proliferation. Over the past decade, this therapeutic approach has demonstrated its safety and clinical feasibility across multiple clinical centers within China through studies and applications involving a substantial number of patients. Clincially, cancer pain is usually caused by tumor growth and associated treatments. As tumors increase in size, they may exert compressive forces on surrounding tissues and nerves. Additionally, chemotherapeutic agents, while targeting tumor cells, can inadvertently damage healthy cells, resulting in inflammatory responses and pain.,, Therefore, therapeutic strategies capable of influencing tumor-associated metabolic processes or reducing treatment-related burden may contribute to symptom improvement. Although Warburg therapy has been suggested to influence tumor metabolism, its specific analgesic effects have not been widely investigated. Therefore, the primary objective of this study was to evaluate the analgesic potential of Warburg therapy through a retrospective analysis of 71 patients with advanced cancer, thereby providing exploratory clinical insights into cancer pain management.