Frontiers in Pharmacology

Anti-tumor mechanism of artesunate

Artesunate (ART) is a classic antimalarial drug with high efficiency, low toxicity and tolerance. It has been shown to be safe and has good anti-tumor effect. Existing clinical studies have shown that the anti-tumor mechanisms of ART mainly include inducing apoptosis and autophagy of tumor cells, affecting tumor microenvironment, regulating immune response, overcoming drug resistance, as well as inhibiting tumor cell proliferation, migration, invasion, and angiogenesis. ART has been proven to fight against lung cancer, hepatocarcinoma, lymphoma, multiple myeloma, leukemia, colorectal cancer, ovarian cancer, cervical cancer, malignant melanoma, oral squamous cell carcinoma, bladder cancer, prostate cancer and other neoplasms. In this review, we highlight the effects of ART on various tumors with an emphasis on its anti-tumor mechanism, which is helpful to propose the potential research directions of ART and expand its clinical application.

Naringenin as potent anticancer phytocompound in breast carcinoma: from mechanistic approach to nanoformulations based therapeutics

The bioactive compounds present in citrus fruits are gaining broader acceptance in oncology. Numerous studies have deciphered naringenin’s antioxidant and anticancer potential in human and animal studies. Naringenin (NGE) potentially suppresses cancer progression, thereby improving the health of cancer patients. The pleiotropic anticancer properties of naringenin include inhibition of the synthesis of growth factors and cytokines, inhibition of the cell cycle, and modification of several cellular signaling pathways. As an herbal remedy, naringenin has significant pharmacological properties, such as anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. The inactivation of carcinogens following treatment with pure naringenin, naringenin-loaded nanoparticles, and naringenin combined with anti-cancer agents was demonstrated by data in vitro and in vivo studies. These studies included colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancers, bladder neoplasms, gastric cancer, and osteosarcoma. The effects of naringenin on processes related to inflammation, apoptosis, proliferation, angiogenesis, metastasis, and invasion in breast cancer are covered in this narrative review, along with its potential to develop novel and secure anticancer medications.

Efficacy and safety analyses of bevacizumab in neoadjuvant chemotherapy for ovarian cancer: a systematic review and meta-analysis

ObjectiveTo assess the efficacy and safety of bevacizumab in neoadjuvant chemotherapy for ovarian cancer through systematic evaluation and meta-analysis.MethodsOnline databases, such as PubMed, Embase, and the Cochrane Library, were searched for relevant articles on the treatment of ovarian cancer patients with interval debulking surgery after neoadjuvant chemotherapy in combination with the bevacizumab regimen using the keywords “Ovarian Neoplasms,” “Bevacizumab,” “Monoclonal antibodies against vascular endothelial growth factor,” “Avastin,” and “Neoadjuvant Therapy.” A meta-analysis of the screened literature, which included randomized controlled trials and cohort studies, was then performed using Stata 15.0 software.ResultsThe meta-analysis included five eligible papers. The test group consisted of 160 patients who received paclitaxel + carboplatin + bevacizumab prior chemotherapy (TCB), whereas the control group consisted 211 patients who received paclitaxel + carboplatin (TC). The results indicate that there was no significant difference between the two groups in terms of the rate of optimal cytoreduction (RR = 1.124, 95% CI: 0.947-1.335, P = 0.182; Heterogeneity: I2 = 40.3%, p = 0.152) and progression-free survival (PFS) (HR = 0.74, 95% CI: 0.48-1.14, p = 0.173; Heterogeneity: I2 = 86%, p = 0.007). Neoadjuvant chemotherapy with bevacizumab did not increase the incidence of adverse events in chemotherapy (RR = 0.88, 95% CI: 0.713-1.088, p = 0.238; Heterogeneity: I2 = 49.5%, p = 0.095). The rate of postoperative complications in the TCB group was comparable to that in the TC group (RR = 0.955, 95% CI:0.672-1.359, p = 0.799; Heterogeneity: I2 = 6.8%, p = 0.368).ConclusionThe use of bevacizumab in neoadjuvant chemotherapy for advanced ovarian cancer was safe and feasible but did not significantly improve the satisfactory tumor reduction rate of interval debulking surgery and had no effect on the prolongation of postoperative PFS. Hence, the use of bevacizumab in preemptive chemotherapy for ovarian cancer should be carefully considered.Systematic Review Registrationhttps://inplasy.com/inplasy-2024-12-0065/, INPLASY2024120065.

Exploratory analysis of the association between body composition albumin-bound paclitaxel induced peripheral neuropathy

Objective This study aimed to examine the relationship between L3 Skeletal Muscle Index (L3SMI) and the incidence and severity of chemotherapy-induced peripheral neuropathy (CIPN) in patients with malignant tumors treated with nab-PTX (albumin-bound paclitaxel) monotherapy or in combination with cisplatin or carboplatin. Methods This study included 52 patients with complete clinical data. The patients’ baseline demographics, disease characteristics, body composition, PG-SGA scale and chemotherapy regimens,was evaluated prior to chemotherapy initiation. Blood samples were collected within 1 hour following the final nab-PTX dose. CIPN was assessed before the third chemotherapy cycle. Patients receiving nab-PTX doses on day 1 were categorized into Group A (n = 36), while those receiving doses on days 1 and 8 were assigned to Group B (n = 16). Group A was further divided into the sarcopenia subgroup (A1) and the non-sarcopenia group (A2), while Group B was divided into the sarcopenia subgroup (B1) and the non-sarcopenia subgroup (B2). The relationship between L3SMI, CIPN incidence and severity were analyzed, and the impact of L3SMI on blood drug concentrations was also investigated. Results The pathological types of enrolled patients included: lung cancer, esophageal carcinoma, cervical cancer, and ovarian cancer. The incidence of CIPN ≥ B grade was significantly higher in sarcopenia subgroups compare with non-sarcopenia in Group A (A1 vs. A2, P = 0.042). Severe CIPN (defined as ≥ grade C) showed a numerically higher occurrence in the sarcopenia subgroups compared to their non-sarcopenia counterparts across groups, although these comparisons did not reach statistical significance. Furthermore, the incidence of CIPN was significantly higher in Group A than in Group B. Among patients receiving nab-PTX doses on day 1, the average dose per kilogram of lean body mass (LBM) was significantly greater in the sarcopenia subgroup compared to the non-sarcopenia subgroup ( P < 0.001). Conclusion Sarcopenia significantly increases the incidence and severity of CIPN in patients undergoing nab-PTX-based chemotherapy. This association may be attributed to the effectively higher dose of nab-PTX per kilogram of lean body mass in patients with sarcopenia, despite the absence of a direct correlation between L3SMI and measured blood drug concentrations. These findings highlight the importance of body composition assessment prior to chemotherapy, as patients with sarcopenia may require enhanced monitoring for CIPN or individualized dosing considerations.