Anticancer research最新文献

{"title":"Management of Chemotherapy-induced Oral Mucositis in Gastrointestinal Malignancies: Evidence From Randomized Controlled Trails.","authors":"Toru Aoyama, Haruhiko Cho, Hideaki Suematsu","doi":"10.21873/anticanres.17680","DOIUrl":"https://doi.org/10.21873/anticanres.17680","url":null,"abstract":"<p><p>Chemotherapy is a key treatment modality for resectable and unresectable gastrointestinal malignancies. Although systemic chemotherapy has clinical benefits, patients with gastrointestinal malignancies experience chemotherapy-related hematological and nonhematological adverse events. Among the various adverse events, chemotherapy-induced oral mucositis (COM) is a common adverse event associated with chemotherapy used for gastrointestinal malignancies. Previous pivotal phase III studies reported that 20%-80% of patients with gastrointestinal malignancies had COM during chemotherapy treatment periods. Once patients have COM, they experience severe discomfort and an impaired ability to eat, swallow, and talk. In addition, the patients with COM need to suspension of chemotherapy or a dose reduction of chemotherapy. Therefore, it is necessary to manage COM to improve both the short- and long-term oncological outcomes. Recently, promising treatments for COM have been reported in randomized trials of gastrointestinal malignancies. This review summarizes the background, current status, and future perspectives of COM treatment in patients with gastrointestinal malignancies.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 8","pages":"3175-3181"},"PeriodicalIF":1.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short- and Long-term Outcomes of Laparoscopic <i>Versus</i> Open Repeat Hepatectomy for Hepatocellular Carcinoma.","authors":"Shogo Fukutomi, Hisamune Sakai, Yuichi Goto, Kazuaki Hashimoto, Ryuta Midorikawa, Shoichiro Arai, Masanori Akashi, Taro Isobe, Takehumi Yoshida, Naoki Mori, Nobuya Ishibashi, Fumihiko Fujita, Toru Hisaka","doi":"10.21873/anticanres.17713","DOIUrl":"https://doi.org/10.21873/anticanres.17713","url":null,"abstract":"<p><strong>Background/aim: </strong>Repeat hepatectomy for recurrent hepatocellular carcinoma (rHCC) can, sometimes, be difficult due to postoperative adhesions and altered liver anatomy. This study aimed to examine the advantages of laparoscopic repeat hepatectomy (LRH) compared to open repeat hepatectomy (ORH).</p><p><strong>Patients and methods: </strong>One hundred and forty-six patients who underwent repeat hepatectomy for rHCC between April 2016 and December 2023 at Kurume University School of Medicine were enrolled. Of these, 105 patients underwent ORH, and 41 underwent LRH. The clinical characteristics and perioperative outcomes of the groups were compared using propensity score-matched (PSM) analysis.</p><p><strong>Results: </strong>In the PSM analysis, there were 13 patients in each group (ORH-PSM group <i>versus</i> LRH-PSM group). There were no significant differences in clinical characteristics between the groups. Intraoperative blood loss (390 ml <i>vs.</i> 30 ml, <i>p</i>=0.004) was lower and the operation time (335 min <i>vs.</i> 208 min, <i>p</i>=0.009) and postoperative hospital stay (15 days <i>vs.</i> 8 days, <i>p</i>=0.0006) were shorter in the LRH-PSM group than in the ORH-PSM group. Although there was no significant difference in the frequency of postoperative complications with a Clavien-Dindo classification grade of IIIa or higher, such problems were only observed in the ORH-PSM group. There was no significant difference in the early recurrence rate (within 6 months) between the ORH-PSM and LRH-PSM groups. Similarly, no significant differences were observed in overall survival (OS) or recurrence-free survival (RFS) between the two groups.</p><p><strong>Conclusion: </strong>LRH showed better short-term outcomes than ORH, while long-term outcomes were comparable.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 8","pages":"3523-3530"},"PeriodicalIF":1.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Standardized Technique for Minimally Invasive Right Posterior Sectionectomy for Hepatocellular Carcinoma: A Propensity Score-matched Study.","authors":"Hisamune Sakai, Yuichi Goto, Shogo Fukutomi, Shoichirou Arai, Ryuta Midorikawa, Kazuaki Hashimoto, Daiki Miyazaki, Masanori Akashi, Nobuya Ishibashi, Koji Okuda, Fumihiko Fujita, Toru Hisaka","doi":"10.21873/anticanres.17711","DOIUrl":"https://doi.org/10.21873/anticanres.17711","url":null,"abstract":"<p><strong>Background/aim: </strong>Minimally invasive right posterior sectionectomy (MIRPS) for hepatocellular carcinoma (HCC) is a technically demanding anatomical liver resection procedure, characterized by restricted visibility and complex hemostatic control. Its effectiveness, compared to that of open surgery, is uncertain. Therefore, this study aimed to compare the perioperative and long-term oncological outcomes of MIRPS and open right posterior sectionectomy (ORPS) for HCC.</p><p><strong>Patients and methods: </strong>Data of 122 consecutive patients, who underwent right posterior sectionectomy as initial treatment for primary HCC from January 2010 to February 2025, were retrospectively analyzed. Patients were allocated to MIRPS and ORPS groups, and surgical outcomes were compared using 1:1 propensity score matching (PSM).</p><p><strong>Results: </strong>After PSM, the MIRPS and ORPS groups comprised 35 patients each. No procedures in the MIRPS group required conversion to open surgery. The MIRPS group demonstrated significantly lower blood loss (119 <i>vs.</i> 548 ml; <i>p</i><0.0001), reduced transfusion rates (0% <i>vs.</i> 11.4%; <i>p</i>=0.0394), shorter operative durations (356 <i>vs.</i> 396 min; <i>p</i>=0.0376), lower postoperative morbidity rates (0% <i>vs.</i> 28.6%; <i>p</i>=0.0006), and shorter postoperative hospital stays (9 <i>vs.</i> 15 days; <i>p</i><0.0001) compared to the ORPS group. The 1-, 3-, and 5-year overall survival rates were 100%, 96.3%, and 96.3% in the MIRPS group and 100%, 91.2%, and 87.9%, in the ORPS group (<i>p</i>=0.3026), respectively. The 1-, 3-, and 5-year recurrence-free survival rates were 88.5%, 77.1%, and 71.6% in the MIRPS group and 85.7%, 65.4%, and 65.4%, in the ORPS group (<i>p</i>=0.5631), respectively.</p><p><strong>Conclusion: </strong>MIRPS reduced perioperative complications, shortened postoperative hospital stay, and achieved recurrence-free and overall survival rates comparable to those of ORPS. Our standardized MIRPS procedure for HCC is considered safe, feasible, and oncologically acceptable for use in selected patients.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 8","pages":"3497-3510"},"PeriodicalIF":1.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Characterization and Therapeutic Implications of MYD88 and CDKN2A in Primary CNS Lymphoma.","authors":"Ryouta Taomoto, Mikiko Aoki, Toshiyuki Enomoto, Tooru Inoue, Kazuki Nabeshima, Makoto Hamasaki, Hiroshi Abe","doi":"10.21873/anticanres.17705","DOIUrl":"https://doi.org/10.21873/anticanres.17705","url":null,"abstract":"<p><strong>Background/aim: </strong>MYD88L265P mutation and CDKN2A loss are among the earliest reported aberrations identified during clonal evolution in primary central nervous system lymphoma (PCNSL), suggesting their role as driver gene mutations critical to the tumorigenesis of this disease. There is no consensus on the relationship between these mutations and prognosis. This study analyzed the incidence of MYD88L265P mutation and CDKN2A homozygous deletion (HD) in PCNSL in relation to prognosis, and whether they could be potential therapeutic targets.</p><p><strong>Materials and methods: </strong>Forty-one patients with intracranially localized diffuse large B-cell lymphomas (DLBCL) with known prognosis were included; MYD88L265P mutation was determined using i-densy, MYD88 protein expression using immunostaining, and CDKN2A HD using fluorescence <i>in situ</i> hybridization (FISH). Overall survival (OS) was calculated using the Kaplan-Meier method.</p><p><strong>Results: </strong>MYD88L265P mutation was found in 35% (7/20) of patients, with a median OS of 14 and 29 months in the mutation-positive and mutation-negative groups, respectively; this was shorter in the mutation-positive group (<i>p</i>= 0.6). Immunostaining was positive in 85% (34/40); median OS was 22 and 28.5 months in the immunostaining-positive and immunostaining-negative groups, respectively; this was shorter in the positive group (<i>p</i>=0.4). CDKN2A HD was found in 73% (27/37) of patients, with median OS of 15 and 35 months, in the HD-positive and HD-negative groups, respectively; shorter in the HD -positive group (<i>p</i>=0.3). When the MYD88L265P mutation and CDKN2A HD were analyzed together, there was a trend toward shorter survival in the group with both mutations (<i>p</i>=0.8).</p><p><strong>Conclusion: </strong>The MYD88L265P mutation was present in 35% of patients, and CDKN2A HD was present in 73%. The MYD88L265 mutation and CDKN2A HD, when considered separately, did not individually demonstrate a clear prognostic correlation; however, prognosis varied notably between patients presenting with both mutations compared to those without. The presence or absence of these mutations may be helpful in future treatment selection when the disease becomes relapsed/refractory after initial therapy.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 8","pages":"3441-3450"},"PeriodicalIF":1.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of Nucleic Acid Medicine Using Autologous Serum-derived Small Extracellular Vesicles for Cancer Metastasis.","authors":"Mai Hazekawa, Takuya Nishinakagawa, Daisuke Ishibashi","doi":"10.21873/anticanres.17720","DOIUrl":"https://doi.org/10.21873/anticanres.17720","url":null,"abstract":"<p><p>Nucleic acids are highly unstable <i>in vivo</i> due to their physicochemical properties, presenting a major obstacle to their clinical application as therapeutics. Consequently, the development of drug delivery systems (DDS) is essential to enable stable transport of nucleic acids within the body and to promote efficient cellular uptake. In cancer therapy in particular, selective delivery technologies capable of targeting diseased organs or tumor cells are critical for minimizing off-target effects and reducing adverse events.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 8","pages":"3577-3586"},"PeriodicalIF":1.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol Derivatives Inhibit Pro-survival Akt Signaling Pathway in Lung Cancer.","authors":"Bhurichaya Innets, Satapat Racha, Zin Zin Ei, Nicharat Sriratanasak, Pithi Chanvorachote","doi":"10.21873/anticanres.17667","DOIUrl":"10.21873/anticanres.17667","url":null,"abstract":"<p><strong>Background/aim: </strong>Akt signaling promotes cancer survival and therapy resistance. This study aimed to modify and improve resveratrol's efficacy by enhancing apoptosis induction in non-small cell lung cancer.</p><p><strong>Materials and methods: </strong>Molecular docking analysis was used to investigate the binding between resveratrol derivatives and the Akt protein. Western blot analysis evaluated the levels of apoptosis markers and signaling proteins.</p><p><strong>Results: </strong>Resveratrol derivative, RD4 (4-(3-hydroxy-4-methoxyphenethyl)-2,6-dimethoxyphenol), shows binding potential to the allosteric site of Akt. After treatment of H460 cells with RD4 for 24 h, increased apoptosis and decreased levels of phosphorylated-Akt (p-Akt) protein were observed. Moreover, the levels of pro-apoptotic protein Bax and cleaved PARP were elevated, while those of the anti-apoptotic protein Bcl-2 were decreased. However, RD2 exhibited moderate effects at high concentrations and RD3 elevated p-Akt expression while exhibiting no apoptotic activity.</p><p><strong>Conclusion: </strong>RD4 suppresses Akt pathways by binding at the allosteric site of Akt. These findings provide a rationale for the design and optimization of novel Akt targeting agents for non-small cell lung cancer treatment.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 7","pages":"3021-3029"},"PeriodicalIF":1.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of Breakthrough Cancer Pain Among Female Patients With Cancer: Knowledge, Management and Characterization in the IOPS-MS Study.","authors":"Anna Crispo, Assunta Luongo, Davide Nocerino, Marco Cascella, Marco Crisci, Francesca Bifulco, Daniela Schiavo, Maurizio Marchesini, Sergio Coluccia, Melania Prete, Alfonso Amore, Egidio Celentano, Sabrina Bimonte, Arturo Cuomo","doi":"10.21873/anticanres.17678","DOIUrl":"10.21873/anticanres.17678","url":null,"abstract":"<p><strong>Background/aim: </strong>Chronic secondary pain from cancer may flare into unexpected acute phases, called breakthrough cancer pain (BTcP). This phenomenon has a moderate-to-severe intensity and short latency between onset and peak of intensity, so clinical and therapeutic implications may be necessary. The Italian Oncologic Pain Multisetting-Multicentric Survey (IOPS-MS) aimed to characterize BTcP in a large number of patients from different settings and assess possible factors influencing its development. Previously, we observed differences according to sex in site, onset and level of BTcP. In this analysis, we assessed differences in non-predictable BTcP between female patients with female-specific cancer (FSC) (including breast and gynecological cancer) and those with non-FSC.</p><p><strong>Patients and methods: </strong>A univariate analysis compared patients with FSC (overall and separately for breast and gynecological cancer) and non-FSC. A multivariate analysis stratified by BTcP phenotype was performed to estimate the main determinants of the risk groups in patients with FSC (overall and separately for breast and gynecological cancer) and non-FSC. Odds ratios and 95% confidence intervals were reported.</p><p><strong>Results: </strong>The FSC group was younger, more often treated in clinics or day hospitals, and had an increased risk of locoregional/metastatic disease than the non-FSC group. Patients with breast cancer were at higher risk of locoregional/metastatic disease, less frequently treated by a palliative specialist and had later BTcP onset compared to the non-FSC group. Significant differences concerning age, care setting and BTcP onset were also found in the group of patients with FSC (overall and separately for breast and gynecological cancer) according to tumor extension.</p><p><strong>Conclusion: </strong>Non-predictable BTcP in patients with FSC presents unique characteristics, particularly regarding pain onset, care settings, and metastasis. Differences between breast and gynecological cancer emphasize the need for tailored pain-management approaches.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 7","pages":"3149-3164"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Benzoxazine-derived Inhibitor Targeting Epithelial-to-Mesenchymal Transition in Lung Cancer.","authors":"Naphatson Phansom, Zin Zin Ei, Bhurichaya Innets, Worawat Wattanathana, Theera Rittirod, Acharawan Thongmee, Keerati Joyjamras, Pithi Chanvorachote","doi":"10.21873/anticanres.17649","DOIUrl":"10.21873/anticanres.17649","url":null,"abstract":"<p><strong>Background/aim: </strong>The epithelial-to-mesenchymal transition (EMT) plays an essential role in lung cancer metastasis. This study aimed to explore the EMT inhibitory effect of the new compound 6,6'-(butylazanediyl) bis (methylene) bis (2,4-dimethylphenol) (2,4-diMBD).</p><p><strong>Materials and methods: </strong>Cell survival and proliferation were determined using cell viability and colony formation assays. Migration was analyzed using a wound-healing assay. The expression of proteins and mRNAs was examined using immunofluorescence assay and real-time quantitative PCR.</p><p><strong>Results: </strong>2,4-diMBD significantly suppressed colony formation and cell migration. In relation to its anti-migratory activity, we found that 2,4-diMBD decreased Snail, Slug, and zinc finger E-box binding homeobox (ZEB) levels at both the mRNA and protein levels, indicating EMT suppression in human lung cancer cells.</p><p><strong>Conclusion: </strong>2,4-diMBD exerts anti-metastatic properties in lung cancer cells <i>via</i> EMT inhibition, and is a promising compound for the treatment of lung cancer.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 7","pages":"2807-2815"},"PeriodicalIF":1.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy and Chemotherapy for Advanced or Recurrent Endometrial Carcinoma.","authors":"John P Micha, Randy D Bohart, Joshua P Gorman, Bram H Goldstein","doi":"10.21873/anticanres.17641","DOIUrl":"10.21873/anticanres.17641","url":null,"abstract":"<p><p>Patients with early-stage endometrial cancer are frequently treated with surgery and radiotherapy or chemotherapy, for which 5-year survival rates approach 95%; conversely, the outcomes for patients with advanced or recurrent endometrial cancer are more inauspicious. Fortunately, the advent of immunotherapy, combined with chemotherapy, has conferred improved survival, especially in endometrial cancer patients with a mismatch repair deficiency (dMMR). We conducted an extensive PubMed search on the topics of endometrial cancer and immunotherapy treatment. The combination of dostarlimab and chemotherapy reportedly coincides with a 2-year progression-free survival (PFS) of 61% compared to a 12-month PFS of 74% for pembrolizumab. Moreover, the follow-up data for dostarlimab extended beyond 44 months and the median overall survival (OS) has not been reached compared to more limited OS data for both pembrolizumab and durvalumab; additionally, dostarlimab's pronounced risk of disease progression or death in both dMMR (70%) and mismatch repair-proficient (pMMR) (46%) patients is considerable. While pembrolizumab, dostarlimab and durvalumab with chemotherapy are associated with beneficial outcomes in advanced-stage or recurrent endometrial cancer, dostarlimab has distinguished itself with unsurpassed survival data compared to pembrolizumab and durvalumab.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 7","pages":"2711-2717"},"PeriodicalIF":1.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone Toxicity Case Report Combining Encorafenib, Cetuximab and WNT974 in a Phase I Trial.","authors":"Mark T J VAN Bussel, Nathalie Bravenboer, Huib VAN Essen, Petur Snaebjornsson, Natasha M Appelman-Dijkstra, Jan Hm Schellens, Frans L Opdam","doi":"10.21873/anticanres.17677","DOIUrl":"10.21873/anticanres.17677","url":null,"abstract":"<p><strong>Background/aim: </strong>More than 90% of colorectal cancers (CRC) have alterations in WNT signaling. Eight to ten percent of patients with metastatic Kirsten rat sarcoma virus - wild type (KRAS-WT) CRC have B-Raf Proto-Oncogene, Serine/Threonine Kinase (BRAF) mutations and do not benefit from epidermal growth factor receptor (EGFR) antibodies. The addition of a porcupine inhibitor could increase the response rate in patients with BRAFV600E-mutated KRAS-WT metastatic CRC (mCRC) with WNT pathway alterations.</p><p><strong>Patients and methods: </strong>We report two cases of severe bone toxicities during treatment with the BRAF inhibitor encorafenib, the EGFR-targeting monoclonal antibody cetuximab, and the porcupine inhibitor WNT974 in the phase 1B study NCT02278133.</p><p><strong>Results: </strong>Patient 1, a 66-year-old man with BRAFV600E-mutated KRAS-WT mCRC and an RNF43 mutation, developed multiple rib fractures and collapse of thoracic vertebrae 10 and 11. Autopsy revealed no metastases at fracture sites; histology demonstrated a thin, porous cortex and poor trabecular bone structure. Immunohistochemistry assessed key WNT pathway components. Patient 2, a 70-year-old man with similar mutations, experienced a toe fracture, multiple rib fractures, osteopenia, and altered bone biomarkers indicative of disrupted bone turnover.</p><p><strong>Conclusion: </strong>The two patients described developed severe bone toxicities including rib fractures, a toe fracture, osteoporotic thoracic collapses, hypercalcemia, and alternated bone biomarkers. These cases highlight the potential skeletal risks associated with dual MAPK and WNT pathway inhibition.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 7","pages":"3137-3147"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}