The article begins with the fundamentals of bile acid physiology. Roughly 95 percent of the bile acids secreted into the intestine are actively reabsorbed in the ileum and recycled back to the liver through the portal vein, a circuit known as the enterohepatic circulation. Primary bile acids, chiefly cholic acid and chenodeoxycholic acid, are synthesized from cholesterol in the liver through pathways driven by the enzymes CYP7A1 and CYP27A1. Once they reach the intestine, gut bacteria convert them by dehydroxylation into secondary bile acids such as deoxycholic acid and lithocholic acid. These microbial derivatives do not simply linger in the gut; they enter the systemic circulation and exert far-reaching effects on host metabolism, intestinal health and inflammatory tone.

The mechanistic heart of the commentary lies in the receptors through which bile acids act. The farnesoid X receptor, or FXR, is a nuclear receptor abundant in liver, intestine and kidney that functions as the body’s bile acid thermostat. When bile acid concentrations rise, FXR binds them and triggers a negative feedback loop that suppresses CYP7A1, curbing further synthesis and preventing toxic accumulation. But FXR’s portfolio extends well beyond metabolic housekeeping. The authors highlight evidence that FXR activation restrains tumor invasion by downregulating matrix metalloproteinases, enzymes that degrade the extracellular matrix, and by dampening pro-inflammatory signaling and cell-cycle progression. The FXR agonist obeticholic acid, already validated in a phase 3 trial for non-alcoholic steatohepatitis, is flagged as a candidate for cancer therapy, potentially in combination with conventional chemotherapy.

A second receptor, TGR5, operates through entirely different circuitry. As a G protein-coupled receptor expressed on immune cells, intestinal epithelial cells and adipose tissue, TGR5 mediates non-genomic, rapid signaling. Its activation raises intracellular cyclic AMP, promotes thermogenesis in brown fat, improves insulin sensitivity and, critically, can halt the runaway proliferation of cancer cells by interfering with cell-cycle progression. TGR5 also modulates macrophages and T cells within the tumor microenvironment, reducing the chronic inflammation that fuels tumor growth. Together, the authors contend, FXR and TGR5 represent a paired molecular handle for therapeutic intervention in bile acid signaling.

The commentary is equally candid about bile acids’ dark side. Secondary bile acids such as deoxycholic acid can be frankly carcinogenic at high concentrations, particularly when they persist in the intestine for extended periods. They induce the production of reactive oxygen species, generating oxidative stress that damages DNA, proteins and lipids and seeds the mutations from which cancers arise—a mechanism considered especially relevant to colorectal cancer. Deoxycholic acid can also activate the Wnt/beta-catenin pathway, driving proliferation while suppressing apoptosis, and both deoxycholic and lithocholic acid trigger the release of pro-inflammatory cytokines such as TNF-alpha and IL-6 through JAK/STAT and NF-kappaB signaling. Chronic inflammation of this kind is regarded as a major pathogenic mechanism in digestive tract cancers, including colorectal and esophageal malignancies.

Woven through the analysis is the bidirectional relationship between bile acids and the gut microbiome. Bile acids shape which microbes thrive: their amphipathic structure allows them to disrupt bacterial membranes, induce DNA damage and provoke oxidative stress in susceptible organisms, while bacteria that express bile acid-metabolizing enzymes gain a survival advantage. In turn, microbes chemically transform bile acids. Bacteria secreting bile salt hydrolases cleave the glycine or taurine groups from conjugated bile acids, converting them into free bile acids with altered solubility and biological activity. Recent work has even uncovered entirely novel microbial bile acid species, such as the succinylated bile acid 3-sucCA, which promotes the growth of the beneficial bacterium Akkermansia muciniphila by regulating its glucose-utilizing NagB enzyme. The authors note that much remains to be learned about how manipulating the bile acid pool reshapes host-microbe communication.

One of the most provocative threads in the commentary concerns taurine, the amino sulfonic acid conjugated to many bile acids. Long celebrated as an antioxidant that neutralizes reactive oxygen species, protects DNA integrity and restrains inflammation by inhibiting NF-kappaB and steering macrophages away from a pro-inflammatory M1 phenotype, taurine has generally been viewed as protective against cancer. Studies cited in the article show it can downregulate cyclins D1 and E and inhibit CDK4 and CDK6, blocking the G1-to-S transition and slowing tumor cell proliferation. Approximately 20 percent of the body’s taurine pool derives from the breakdown of taurine-conjugated bile acids, tying this amino acid intimately into bile acid metabolism.

Yet the picture is not so simple. The authors spotlight a 2024 Cell study identifying the taurine transporter SLC6A6 as a determinant of gastric cancer progression and recurrence. Tumor cells overexpress SLC6A6 and outcompete CD8-positive T cells for taurine, starving the immune cells and driving their exhaustion. Mechanistically, taurine depletion in T cells heightens endoplasmic reticulum stress, activating PERK-JAK1-STAT3 signaling and the transcription factor ATF4, which switches on multiple immune checkpoint genes. In gastric cancer, chemotherapy can upregulate the transcription factor SP1, further boosting SLC6A6 expression and intensifying this nutritional competition—a mechanism that may underlie both immune dysfunction and chemotherapy resistance. Taurine supplementation, the authors suggest, could serve as an adjunct therapy by protecting T cells and enhancing chemotherapy efficacy, but only in the right context.

That context-dependence is the commentary’s central message. Taurine’s function, like that of bile acids generally, is jointly determined by microenvironmental conditions, cell-type-specific metabolic capacity and host immune status—not by any single molecular property. This framing aligns with the integrative medicine philosophy articulated by Academician Daiming Fan, whose concepts of anti-cancer treatment, tumor control and life support emphasize restoring the body’s intrinsic regulatory forces rather than simply eliminating lesions. From this perspective, bile acid dysregulation is both a marker and a driver of the systemic imbalance that underlies cancer, and the liver-gut-immune axis becomes a concrete intervention point: modifying bile acid composition through diet, nutritional support or metabolic regulation may help rebuild an antitumor immune environment and ease treatment-related side effects.

The authors conclude that a multidimensional strategy centered on bile acid signaling offers a route from treating cancer as a local lesion toward managing it as a disorder of systemic homeostasis. By integrating molecular mechanisms with lifestyle and supportive therapies, and by individualizing approaches to taurine and bile acid pathways rather than applying blanket supplementation or inhibition, the framework points toward a more holistic, patient-centered integrative oncology—one in which the humble detergent molecules of digestion are recognized as key arbiters of life and disease.

Subject of Research: The roles of bile acids, their receptors and taurine metabolism in cancer biology and integrative oncology

Article Title: An integrative view of bile acids

Article References: Bai, X., Liu, B., Liu, L., Lu, Y., & Zhao, X. (2026). An integrative view of bile acids. Holistic Integrative Oncology, 5(1), Article 67. https://doi.org/10.1007/s44178-026-00290-9

Image Credits: AI Generated

DOI: 10.1007/s44178-026-00290-9

Keywords: bile acids, FXR, TGR5, gut microbiota, taurine, SLC6A6, tumor microenvironment, colorectal cancer, obeticholic acid, integrative oncology, bile salt hydrolase, immune evasion

The review places music intervention within a biopsychosocial model of medicine, which recognizes that cancer affects biological systems as well as emotions, behavior, relationships and daily functioning. A diagnosis can trigger fear and uncertainty, while repeated procedures, treatment toxicity, financial pressure and concerns about recurrence can intensify psychological distress. These experiences can influence sleep, pain perception, treatment participation and recovery. The authors distinguish among music therapy delivered by trained professionals, medical music listening in which healthcare staff provide recorded music, and recreational musical activities led by musicians or clinical personnel. The distinctions matter because the interventions differ in intensity, personalization, therapeutic goals and the expertise required to deliver them.

Evidence summarized in the review suggests that the most consistent benefits occur when music is integrated with clinical assessment and patient preference rather than imposed as a generic soundtrack. During chemotherapy, for example, patients may listen to selected music for about an hour while receiving routine care. In studies of procedures such as peripherally inserted central catheter placement, sessions lasting about 30 minutes were associated with lower anxiety and changes in vital signs, including diastolic blood pressure and heart rate. A randomized study involving 304 people with lung cancer reported benefits when music accompanied routine care during catheter placement and afterward. Research involving children with leukemia similarly linked music therapy during catheter treatment with improved mood, less pain and reduced sedative use, although the review emphasizes that intervention designs and outcomes vary.

Music may also help patients manage the cognitive and emotional burden that accompanies cancer treatment. Chemotherapy-associated cognitive difficulties can involve memory, attention, learning and executive function, and these changes may compound the distress of diagnosis. The review cites a randomized study of 27 breast cancer survivors in which eight weeks of either meditation or classical music listening improved cognitive function, memory and verbal fluency. It also discusses postoperative brain-tumor research in which cognitive training combined with music intervention was associated with better cognitive function, sleep and psychological status. The proposed value of music in these settings is partly communicative: singing, listening, guided imagery or improvisation can give patients a manageable way to express emotions, focus attention and participate actively in their care.

Symptom control is the largest area covered by the review. Anxiety and fear can rise before imaging, surgery, chemotherapy or other procedures, particularly when patients must remain still in an enclosed or noisy environment. Music-guided relaxation before or during a procedure may reduce arousal and help patients complete care. In one study of 750 outpatient chemotherapy patients, participants who selected their own music experienced improvements in negative emotions and pain measures compared with routine care. A separate pilot trial combining face-to-face music listening with progressive muscle relaxation for three weeks reported lower anxiety, depression and stress at the end of treatment, with benefits still evident at follow-up. However, the evidence is not uniform: a meta-analysis of six randomized trials found improvements in anxiety and quality of life before chemotherapy but no substantial effect on depression.

Studies of chemotherapy-induced nausea and vomiting point to a similarly promising but qualified role. Antiemetic drugs remain central to prevention and treatment, yet nausea is influenced by anticipation, anxiety, sensory cues and a patient’s interpretation of symptoms. The review describes a meta-analysis of 10 studies that found music reduced the incidence and severity of anticipated nausea and vomiting, while noting continuing uncertainty about acute symptoms during or immediately after chemotherapy. Other analyses reported lower nausea and vomiting scores and a reduced likelihood of at least grade-one symptoms when individualized music was added to standard nursing care, particularly in gastrointestinal cancer. The findings suggest that timing, musical preference, therapeutic guidance and the patient’s prior experience may all shape the response, making repeated assessment important.

Pain, sleep and fatigue are additional targets. In palliative care, music selected according to patient preference and combined with medication was associated with lower pain and greater comfort in a randomized study of 60 people. After lung-cancer surgery, music therapy alongside intravenous sufentanil analgesia was linked to lower pain scores and reduced dose and administration frequency over the first postoperative day. Music does not act as a substitute for analgesics, but relaxation and attentional engagement may alter how pain is perceived and help patients use other treatments more effectively. Sleep studies have reported benefits after sessions of roughly 30 minutes; a meta-analysis of hospitalized patients found improved sleep quality, and studies in breast and lung cancer suggested additional gains when music was combined with exercise or psychological support.

The review also describes music as a possible bridge between symptom management and physical rehabilitation. After breast-cancer surgery, programs combining music-guided relaxation with limb exercises were associated with improved shoulder movement, reduced swelling and fewer discomfort symptoms. In lung rehabilitation, music can provide rhythm or structure for breathing exercises, relaxation and vocal activities. Evidence from pulmonary rehabilitation, cardiothoracic surgery and postoperative non-small-cell lung cancer care suggests potential improvements in respiratory muscle performance, lung expansion, functional indices and quality of life. These interventions require clinical judgment: therapists must consider cardiovascular and pulmonary function, pain during breathing, the prescribed inhalation-to-exhalation ratio, fatigue and the patient’s preferences. Severe respiratory or cardiovascular problems require coordination with the treating physician.

Combining music with other supportive approaches may produce broader effects than music alone. The review cites studies pairing it with mindfulness-based stress reduction, progressive muscle relaxation, aromatherapy, acupressure and aerobic exercise. In patients with osteosarcoma, music combined with mindfulness practices was associated with improvements in pain, anxiety and sleep. Among women undergoing breast-cancer treatment, aromatherapy plus music relaxation performed better for perioperative pain and anxiety than either intervention alone. Yet the authors caution that many studies are small, use different musical formats and measure short-term outcomes, making direct comparison difficult. Music intervention should therefore be viewed as patient-centered supportive care, not an anticancer treatment or a guaranteed method of changing survival. Larger, rigorously designed trials are needed to establish which patients benefit, which delivery methods work best, how often sessions should occur and whether gains persist. For now, the review argues that music offers a relatively simple, safe and adaptable addition to multidisciplinary oncology care when integrated with medical treatment and individualized assessment.

The clinical rationale for these interventions extends beyond distraction. Within the biopsychosocial framework described by the review, music can engage emotional, cognitive and social dimensions of illness at the same time. It may provide a familiar structure during periods in which diagnosis and treatment feel unpredictable, while also creating an avenue for communication when patients find direct discussion difficult. In a therapeutic setting, a patient’s responses to a song, rhythm or musical activity can help reveal distress, preferences and changing needs. This makes music potentially relevant not only to symptom relief but also to the human relationship at the center of supportive oncology.

Delivery should be matched to the purpose of care. Passive listening may be practical in an infusion unit, before a procedure or during rest, whereas music therapy involves a qualified practitioner who adapts the session and uses music within a defined treatment process. Active approaches, such as singing or other guided musical participation, may encourage agency and interaction, but they are not interchangeable with recorded music. The review’s comparison of studies found more consistently favorable findings for interventions provided by trained music therapists, while results for medical music listening were less uniform. This distinction is important when hospitals interpret evidence or plan services.

Patient choice is another clinically meaningful variable. Musical familiarity, cultural background, age, language, prior experiences and current mood can influence whether a session feels calming, irritating or emotionally overwhelming. The review therefore supports flexible strategies rather than a single preferred genre or universal protocol. Clinicians can ask what the patient normally listens to, whether music is welcome at that moment and whether listening should be uninterrupted or combined with conversation, breathing practice or rehabilitation. Patients should also be able to stop an intervention, particularly when music evokes unwanted memories or increases discomfort.

Implementation is best understood as part of coordinated supportive care rather than an isolated activity. Oncology nurses, physicians, rehabilitation professionals, palliative-care teams and music therapists may use different observations to determine whether a session is helping. Repeated assessment can include the patient’s reported anxiety, pain, nausea, sleep or fatigue, together with participation in treatment and functional recovery. Such monitoring can identify when music is useful and when another intervention is needed. It also helps separate immediate comfort from longer-term outcomes, a necessary distinction because the reviewed studies varied in intervention length, cancer type, setting and outcome measurement.

The review’s findings support continued clinical investigation, but they do not establish that music directly alters tumor biology or reliably extends survival. Most of the evidence concerns patient-reported symptoms, psychological states, physiological responses or rehabilitation measures. Future studies would benefit from clearer descriptions of therapist training, session content, timing, dose, patient selection and usual-care comparisons. Consistent outcome measures and longer follow-up could clarify whether short-term reductions in distress translate into sustained improvements in functioning, adherence or quality of life. Until then, music is most appropriately offered as an individualized, low-burden complement to evidence-based cancer treatment and palliative care.

Subject of Research: Clinical use of music interventions to support psychological, physical and rehabilitation outcomes in cancer patients

Article Title: The integrated application of music intervention in clinical practice for cancer patients

Article References: Zhang, F., Li, X., Wang, J., Ma, M., Xu, Y., & Hong, L. (2026). The integrated application of music intervention in clinical practice for cancer patients. Holistic Integrative Oncology, 5(1), Article 71. https://doi.org/10.1007/s44178-026-00271-y

Image Credits: AI Generated

DOI: 10.1007/s44178-026-00271-y

Keywords: music therapy, cancer care, integrative oncology, symptom management, anxiety, pain, sleep, chemotherapy, rehabilitation, quality of life, integrated, application

This exploratory, randomized pilot study, conducted across multiple centers, sought to assess the safety and immunomodulatory effects of BJIKT—a well-known herbal remedy used traditionally in East Asian medicine for its anti-inflammatory and fatigue-relieving properties. The study specifically targeted patients with advanced NSCLC receiving atezolizumab monotherapy, an anti-PD-L1 checkpoint inhibitor widely used in clinical oncology. By integrating this herbal medicine with modern immunotherapy, the researchers aimed to explore if BJIKT could mitigate some common treatment-related adverse events such as fatigue and muscle wasting, while potentially enhancing immune activation.

The trial enrolled 28 patients who were randomly assigned to receive either BJIKT or a placebo, with both groups continuing standard atezolizumab therapy. Throughout the study, the team meticulously monitored adverse events (AEs), immune-related adverse events (irAEs), fatigue levels, and the progression of muscle loss, aiming to uncover interactions between the herbal treatment and immune checkpoint blockade. Beyond clinical symptomatology, a subset of patients underwent detailed immune profiling to shed light on the cellular immune mechanisms potentially influenced by BJIKT.

Findings revealed that adverse events were prevalent in over half of participants, a not unexpected outcome given the aggressive nature of cancer immunotherapy. Intriguingly, the BJIKT group exhibited a higher incidence of AEs (64.29%) compared to the placebo group (42.86%), though the majority of these events were mild to moderate and resolved by the conclusion of the trial. This raises important safety considerations but also underscores the complex interplay between herbal compounds and immune modulation therapies, warranting further pharmacovigilance in larger cohorts.

From an efficacy standpoint, the objective response rate (ORR) and disease control rate (DCR) were numerically higher in the BJIKT-treated group—16.67% versus 8.33% for ORR and 41.67% versus 25% for DCR compared to placebo—though these differences did not reach statistical significance. These encouraging trends suggest that BJIKT might augment tumor growth control during ICI therapy, possibly by enhancing the host immune system’s anti-tumor prowess. Nonetheless, the lack of statistical significance tempers overenthusiasm and highlights the exploratory nature of this pilot trial.

One of the more compelling aspects of the study lies in its immunological analyses. The researchers detected a significant reduction in PD-1 positive CD8+ T cells in patients receiving BJIKT, implying a decrease in T cell exhaustion—a state where T cells become less functional due to chronic antigen exposure, commonly seen in cancer. This finding indicates that BJIKT may reinvigorate cytotoxic T cells, a pivotal cell population responsible for directly attacking tumor cells. Conversely, while PD-1+ CD4+ T cell numbers also declined with BJIKT, this change was not statistically significant, suggesting a selective modulation of T cell subsets.

Beyond T cells, a notable increase in natural killer (NK) cell counts was observed in the BJIKT group. NK cells constitute an essential arm of innate immunity, capable of recognizing and destroying cancer cells without prior sensitization. The elevation of these effector cells may reflect enhanced innate immune surveillance facilitated by BJIKT, potentially contributing to improved tumor control in NSCLC. Moreover, immune profiling revealed trends toward increased activation of CD4+ T cells and the overall proportion of CD3+CD4+ cells, indicating a broader stimulation of helper T cell-mediated immune orchestration during treatment.

BJIKT’s capacity to alleviate fatigue and muscle loss—common debilitating symptoms experienced by patients undergoing immunotherapy—was also examined. While the herbal treatment showed a trend toward mitigating these symptoms, the changes were not statistically significant. Still, these observations correlate with BJIKT’s traditional use in managing fatigue and chronic inflammation, suggesting it may hold supportive care value for NSCLC patients in future integrative oncology frameworks.

The study’s design as a randomized, placebo-controlled pilot trial provides valuable preliminary insights but naturally comes with limitations inherent to small sample sizes, which restrict the statistical power to detect definitive effects. However, the findings lay a foundation for subsequent larger-scale investigations to validate BJIKT’s immunomodulatory benefits and safety profile in combination with ICIs. Such follow-up trials could also dissect the molecular pathways involved, potentially revealing novel complementary mechanisms by which traditional herbal medicine synergizes with cutting-edge immunotherapies.

Notably, the interplay between BJIKT and the complex tumor-immune microenvironment highlights the exciting potential of combining phytochemicals with immuno-oncological agents. This fusion of ancient herbal wisdom with modern molecular oncology could pave the way for innovative, multi-modal cancer treatment regimens aimed at boosting efficacy while minimizing toxicities. Furthermore, the selective immune effects observed with BJIKT—specifically the reduction of immune exhaustion markers and augmentation of NK cells—underscore the importance of immune homeostasis in achieving sustained anti-tumor responses.

From a clinical perspective, this research advocates for integrating complementary therapies like BJIKT into the multidisciplinary care of NSCLC patients receiving ICIs. Positive modulation of immune function and alleviation of adverse symptom burden could improve patient adherence to therapy and quality of life. However, the necessity for rigorous validation studies, standardized herbal preparations, and mechanistic elucidations cannot be overstated before broad application.

Additionally, the trial was registered with the Clinical Research Information Service of Korea, ensuring adherence to ethical and methodological standards. Such transparency not only bolsters credibility but also facilitates collaboration, data sharing, and global efforts to refine cancer therapies. Future studies may build upon this pilot trial to design adaptive, biomarker-driven approaches targeting immune exhaustion and enhancing effector cell function in NSCLC and beyond.

In summary, this pioneering research sheds light on the prospective role of Bojungikki-Tang as an adjunctive agent capable of finely tuning the immune landscape in NSCLC patients undergoing atezolizumab therapy. While conclusive evidence remains forthcoming, the reported reductions in immune exhaustion markers and elevations in innate immune effectors inspire optimism for harnessing herbal pharmacology in the fight against lung cancer. This convergence of traditional medicine and immuno-oncology represents a fertile frontier warranting enthusiastic scientific pursuit.

As the oncology community continues to grapple with the challenges of maximizing immunotherapy benefit, findings like these energize the search for integrative strategies. Bojungikki-Tang’s ancient formula, reinterpreted through the lens of modern immune profiling, exemplifies how history may inform future breakthroughs. Clinical trials with larger cohorts, longer follow-up, and multi-omics analyses will be imperative to validate these preliminary signals and ultimately translate them into robust, patient-centered cancer care innovations.

Subject of Research: Effects of Bojungikki-Tang on immune response and clinical outcomes in NSCLC patients receiving immune checkpoint inhibitors

Article Title: Effects of Bojungikki-Tang on immune response and clinical outcomes in NSCLC patients receiving immune checkpoint inhibitors: a randomized pilot study

Article References:
Ko, M.M., Na, S.W., Yi, J.M. et al. Effects of Bojungikki-Tang on immune response and clinical outcomes in NSCLC patients receiving immune checkpoint inhibitors: a randomized pilot study. BMC Cancer 25, 1229 (2025). https://doi.org/10.1186/s12885-025-14629-4

Image Credits: Scienmag.com

DOI: https://doi.org/10.1186/s12885-025-14629-4