Targeted Oncology最新文献

{"title":"PROteolysis TArgeting Chimera (PROTAC) Estrogen Receptor Degraders for Treatment of Estrogen Receptor-Positive Advanced Breast Cancer.","authors":"Erika P Hamilton, Rinath M Jeselsohn, Linda T Vahdat, Sara A Hurvitz","doi":"10.1007/s11523-025-01137-5","DOIUrl":"10.1007/s11523-025-01137-5","url":null,"abstract":"<p><p>The estrogen receptor (ER) signaling pathway is a key driver of breast cancer, primarily through the activation of genes that promote tumor cell survival and growth. The recommended first-line treatment for ER-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer is endocrine therapy plus a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. However, most patients experience disease progression, and there is no clear standard of care in the second-line setting. Thus, novel treatments in the advanced setting are needed. In this narrative review, we describe the unique mechanisms of action of a new class of drugs called PROteolysis TArgeting Chimera (PROTAC) ER degraders. Unlike other ER-targeted therapies, these small molecules harness the body's primary intracellular natural protein disposal machinery, the ubiquitin-proteasome system, to directly induce ER degradation. Vepdegestrant (ARV-471) is the furthest advanced PROTAC ER degrader currently in clinical development. Preclinical data demonstrate increased tumor growth inhibition with vepdegestrant alone or in combination with CDK4/6 inhibitors compared with the selective ER degrader fulvestrant. In a first-in-human phase 1/2 clinical study, vepdegestrant administered orally as monotherapy or in combination with palbociclib showed promising clinical activity and a favorable safety profile in patients with heavily pretreated ER+/HER2- advanced breast cancer. Several other PROTAC ER degraders (AC699, ERD-3111, ERD-4001, and HP568) are in early development and have demonstrated activity in preclinical breast cancer models, with some recently entering clinical trials. The data highlight the potential for PROTAC ER degraders to be a new backbone therapy in breast cancer.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"431-444"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Olaparib Monotherapy or in Combination with Abiraterone for the Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC) and a BRCA Mutation.","authors":"Fred Saad, Andrew J Armstrong, Neal Shore, Daniel J George, Mototsugu Oya, Mikio Sugimoto, Rana R McKay, Maha Hussain, Noel W Clarke","doi":"10.1007/s11523-025-01146-4","DOIUrl":"10.1007/s11523-025-01146-4","url":null,"abstract":"<p><p>Treatment strategies to improve outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) are evolving. Of particular interest are therapies that target DNA damage responses in tumor cells by inhibiting poly(ADP-ribose) polymerase (PARP) activity. Several PARP inhibitors have recently received regulatory approval for the treatment of patients with mCRPC, of which olaparib was the first for prostate cancer. Olaparib received approval as a monotherapy following the PROfound study (NCT02987543) and in combination with abiraterone following the PROpel study (NCT03732820) for mCRPC. Both PROfound (homologous recombination repair mutation biomarker-selected) and PROpel (biomarker unselected) patients demonstrated statistically significant longer radiographic progression-free survival (rPFS) with olaparib versus their respective control arms in the intention-to-treat population. In both studies, the greatest clinical benefit with olaparib was seen in patients with BRCA1 and/or BRCA2 mutations (BRCAm): PROfound rPFS hazard ratio (HR) 0.22 (95% confidence interval [CI] 0.15-0.32); PROpel rPFS HR 0.23 (95% CI 0.12-0.43). Clinical benefit was also observed in terms of overall survival: PROfound HR 0.63 (95% CI 0.42-0.95); PROpel HR 0.29 (95% CI 0.14-0.56). We provide a comprehensive overview of the utility of olaparib for patients with mCRPC harboring a BRCAm. Key clinical and safety data in BRCAm subgroup populations are discussed, predominantly based on findings from PROfound and PROpel, as well as investigator-initiated studies, to help inform treatment decision-making in this patient population. We also discuss the importance of genetic testing to identify patients who may optimally benefit from treatment with olaparib, either as a monotherapy or in combination with abiraterone.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"445-466"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating the Landscape of Resistance Mechanisms in Antibody-Drug Conjugates for Cancer Treatment.","authors":"Gloria Lalli, Ilaria Sabatucci, Mariachiara Paderno, Fabio Martinelli, Mauro Signorelli, Matteo Maruccio, Giampaolo Di Martino, Giovanni Fucà, Domenica Lorusso","doi":"10.1007/s11523-025-01140-w","DOIUrl":"10.1007/s11523-025-01140-w","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) are an innovative approach in cancer therapy, combining the specificity of monoclonal antibodies (mAb) with the cytotoxic effect of chemotherapy agents. Despite the remarkable efficacy demonstrated in clinical studies, primary and secondary resistance to ADCs represent a concern and a significant challenge. Known resistance mechanisms mainly involve the targeted tumor antigen; the internalization, trafficking, and cleavage processes; the cytotoxic payload; and the intrinsic tumor cell dynamics of cell death and cell signaling. Key strategies to overcome these resistance mechanisms include the use of antibodies targeting the same antigen but with different payloads, developing dual-payload ADCs that target multiple cellular pathways, switching from non-cleavable to cleavable linkers, and combining ADCs with other therapies such as immune checkpoint inhibitors and antiangiogenic agents. By improving our understanding of what underlies the mechanisms of resistance to ADCs and implementing and studying systems to overcome these mechanisms, as well as using innovative therapeutic combinations, ADCs have the potential to continue to play a fundamental role in the treatment of tumors, especially refractory ones, providing patients with more effective and long-lasting therapeutic options, as well as better outcomes.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"419-430"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of First-Line Treatments for Advanced Renal Cell Carcinoma: A Bayesian Network Meta-analysis of Objective Response, Progression-Free Survival, and Overall Survival.","authors":"Manuela Schmidinger, Pratik P Rane, Kevin Yan, Eric Druyts, Joseph Burgents, Murali Sundaram, Avivit Peer","doi":"10.1007/s11523-025-01147-3","DOIUrl":"10.1007/s11523-025-01147-3","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of this study was to indirectly compare pembrolizumab + lenvatinib to other treatments of interest for first-line advanced renal cell carcinoma (aRCC).</p><p><strong>Methods: </strong>A systematic literature review searched EMBASE, MEDLINE, and CENTRAL databases for relevant randomized controlled trials of interest up to 30 January 2024, with an updated search conducted on 17 March 2025. A fixed effect Bayesian network meta-analysis (NMA) was conducted to determine the relative treatment effects for overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).</p><p><strong>Results: </strong>When comparing against other immune checkpoint inhibitors (ICI), a statistically significant improvement in PFS was demonstrated between pembrolizumab + lenvatinib compared with nivolumab + ipilimumab (hazard ratio (HR) = 0.53; 95% credible interval (CrI): 0.40-0.71), avelumab + axitinib (HR = 0.71; 95% Crl: 0.53-0.94), atezolizumab + bevacizumab (HR = 0.54; 95% CrI: 0.40-0.73), and pembrolizumab + axitinib (HR = 0.69; 95% CrI: 0.51-0.91). Treatment with pembrolizumab + lenvatinib resulted in no statistically significant difference between pembrolizumab + lenvatinib and other combination ICI-based therapies for OS. A statistically significant higher ORR was shown for pembrolizumab + lenvatinib compared with nivolumab + ipilimumab (odd ratio (OR) = 3.29; 95% Crl: 2.21-4.93), pembrolizumab + axitinib (OR = 1.92; 95% CrI: 1.27-2.94), atezolizumab + bevacizumab (OR = 4.05; 95% Crl: 2.71-6.05), bempegaldesleukin + nivolumab (OR = 6.20; 95% CrI: 3.69-10.48), and nivolumab (OR = 5.92; 95% CrI: 2.70-13.24).</p><p><strong>Conclusions: </strong>The overall population analysis indicated that pembrolizumab + lenvatinib improves PFS and ORR compared with other approved ICI combination therapies in first-line aRCC. No significant differences in OS were observed between pembrolizumab + lenvatinib and other combination immune checkpoint inhibitor-based therapies.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"375-387"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CIBMTR Registry Data on Inotuzumab Ozogamicin Treatment in Patients with ALL Who Proceeded to Hematopoietic Stem Cell Transplant-A Podcast.","authors":"Marcos de Lima, David I Marks","doi":"10.1007/s11523-025-01129-5","DOIUrl":"10.1007/s11523-025-01129-5","url":null,"abstract":"<p><p>Inotuzumab ozogamicin (InO) was approved for the treatment of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) on the basis of the phase 3 INO-VATE trial, which found that treatment-related mortality (TRM), primarily due to hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), was higher among patients who received InO versus standard therapy and proceeded to allogeneic hematopoietic stem cell transplantation (HSCT). Here, we use real-world data obtained from the Center for International Blood and Marrow Transplant Research database to evaluate post-HSCT outcomes in adult patients with ALL who received InO from 18 August2017 to 18 August 2022. Post-HSCT follow-up data were available for 244 patients with ALL (including 156 with R/R ALL) who received InO. VOD incidence within 100 days of HSCT was 14% among all patients and 18% among patients with R/R ALL. These data are consistent with a pooled analysis of the phase 1/2 study 1010 and the phase 3 INO-VATE trial that reported VOD in 19% of patients who received InO and proceeded to HSCT (n = 101). The current study demonstrates VOD incidence among patients receiving InO prior to HSCT in the real world is similar to that reported in clinical trials. Supplementary file1 (MP4 165809 KB).</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"371-374"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of EGFR Mutation Subtypes on Response to Chemoimmunotherapy and Chemotherapy in Non-Small-Cell Lung Cancer After EGFR-TKI Failure.","authors":"Kenji Morimoto, Tadaaki Yamada, Naoki Furuya, Hisashi Tanaka, Akihiro Yoshimura, Tomohiro Oba, Makoto Hibino, Takahito Fukuda, Yasuhiro Goto, Akira Nakao, Shinsuke Ogusu, Yuta Okazaki, Taishi Harada, Takayo Ota, Ken Masubuchi, Koji Mikami, Tae Hata, Shoki Matsumoto, Ryoichi Honda, Koji Date, Yusuke Chihara, Hayato Kawachi, Koichi Takayama","doi":"10.1007/s11523-025-01144-6","DOIUrl":"10.1007/s11523-025-01144-6","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of immune checkpoint inhibitor (ICI) monotherapy on non-small-cell lung cancer (NSCLC) varies by epidermal growth factor receptor (EGFR) mutation subtypes. However, the impact of these subtypes on the clinical outcomes of chemoimmunotherapy (Chemo+ICI) or platinum-based chemotherapy (Chemo) in real-world practice remains unclear.</p><p><strong>Objective: </strong>This study evaluated the impact of EGFR mutation subtypes on NSCLC treatment outcomes of Chemo and Chemo+ICI.</p><p><strong>Patients and methods: </strong>We retrospectively analyzed patients with advanced or recurrent EGFR-mutant NSCLC from 20 institutions between January 2017 and July 2022. Patients received Chemo with or without ICI after failure of EGFR-tyrosine kinase inhibitors. Common EGFR mutations were categorized as exon 19 deletions and exon 21 L858R mutations.</p><p><strong>Results: </strong>Among the 403 patients, 205 (50.9%) had exon 19 deletions, and 198 (49.1%) had L858R mutations. For patients with L858R mutations, Chemo+ICI significantly improved progression-free survival (PFS) compared with Chemo (7.0 vs 5.3 months; p = 0.04). However, no significant difference in PFS was observed between treatments for patients with exon 19 deletions (6.7 vs 6.0 months; p = 0.96). Multivariate analysis identified Chemo+ICI as an independent predictor of PFS in patients with L858R mutations (hazard ratio 0.63; 95% confidence interval 0.43-0.92; p = 0.02).</p><p><strong>Conclusions: </strong>Among patients with common EGFR mutation subtypes, those with L858R mutations demonstrated significantly improved PFS with Chemo+ICI than with Chemo. These findings suggest that Chemo+ICI may offer a more effective treatment option for patients with L858R-mutant NSCLC, warranting further investigation in prospective studies.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"531-541"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Toxicity of Pemigatinib in Advanced Cholangiocarcinoma Harboring FGFR Fusions or Rearrangements: A Systematic Review and Meta-analysis.","authors":"Erman Akkus, Hatime Arzu Yasar, Lorenza Rimassa, Angela Lamarca","doi":"10.1007/s11523-025-01142-8","DOIUrl":"10.1007/s11523-025-01142-8","url":null,"abstract":"<p><strong>Background: </strong>The efficacy and safety of pemigatinib in advanced cholangiocarcinoma (aCCA) were presented in phase I-II trials and retrospective reports, with small sample sizes and variable results.</p><p><strong>Methods: </strong>A systematic literature search included studies investigating the efficacy/safety of pemigatinib in aCCA harboring FGFR fusions/rearrangements. Primary outcomes were objective response rate (ORR) and treatment-related adverse events (AEs). A pooled proportion meta-analysis was performed.</p><p><strong>Results: </strong>Three hundred and twenty-seven patients in eight studies were included (three phase-II, one phase-I/II, two phase-I, and two retrospective). In the pooled analyses, the median age was 58.9 years (95% confidence interval (CI): 51.9-65.8); 33.4% (95% CI: 28.1-39.0) were male. Pemigatinib was the second-line treatment in 58.5% (95% CI: 52.7-64.1) and was beyond second-line in the remaining. ORR was 42.2% (95% CI: 35.9-48.7) (I²:48.4%) and disease control rate (DCR) was 86.5% (95% CI: 81.6-90.5) (I²: 58.8%). Median progression-free survival (PFS) was 7.8 months (95% CI: 6.2-9.4) (I²: 11.6%). Two studies reported overall survival (OS) (median 17.5 and 17.1 months). The most common AEs (any grade) were hyperphosphatemia (46%), dysgeusia (33.2%), alopecia (31.4%), fatigue (30.9%), stomatitis (28.5%), and diarrhea (27.5%). Cumulative eye and nail toxicities were observed in 32.5% and 40.9%, and retinal detachment in 5.5%.</p><p><strong>Conclusion: </strong>This analysis emphasizes the FGFR alteration testing and pemigatinib use in the second-line and beyond treatment of aCCA.</p><p><strong>Registration id (prospero): </strong>CRD42024627459.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"389-403"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy for Renal Cell Carcinoma-What More is to Come?","authors":"Zachary A Yochum, David A Braun","doi":"10.1007/s11523-025-01143-7","DOIUrl":"10.1007/s11523-025-01143-7","url":null,"abstract":"<p><p>The treatment of renal cell carcinoma (RCC), a malignancy that is typically chemoresistant, has drastically evolved with the introduction of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) and immune checkpoint inhibitors (ICIs). The introduction of ICI-based regimens has significantly improved outcomes for patients with metastatic RCC. Currently, first-line therapy for patients with metastatic RCC involves multiple ICI-based regimens, either dual ICIs (with anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA- 4) and anti-programmed cell death- 1 (PD- 1) therapies) or anti-PD- 1 therapy in combination with VEGFR TKIs. Despite improving patient outcomes with ICI-based regimens, durable responses remain uncommon, highlighting the need for innovative treatment strategies. In this review, we highlight the current standard of care ICI-based regimens followed by ongoing clinical trials with novel combinations of existing FDA-approved agents and targets. We also discuss novel immunotherapies currently in clinical trials, which aim to improve antitumor T cell immunity either by improving T cell activation or T cell navigation to the tumor microenvironment. The incorporation of these novel therapies offers the potential to improve RCC patient outcomes, particularly by enhancing the durability of treatment responses.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"467-483"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 1b/2 Study of the Anti-CD47 Antibody Magrolimab with Cetuximab in Patients with Colorectal Cancer and Other Solid Tumors.","authors":"Cathy Eng, Nehal J Lakhani, Philip A Philip, Charles Schneider, Benny Johnson, Adel Kardosh, Mark P Chao, Amita Patnaik, Fadi Shihadeh, Yeonju Lee, Kai Song, Denise Jin, Yanan Huo, Michael Howland, George A Fisher, J Randolph Hecht","doi":"10.1007/s11523-025-01130-y","DOIUrl":"10.1007/s11523-025-01130-y","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy plus epidermal growth factor receptor (EGFR) inhibitors, such as cetuximab, is standard therapy for KRAS wild-type (KRASwt) colorectal cancer (CRC); however, responses are infrequent. Magrolimab is a monoclonal antibody targeting CD47, an antiphagocytic signal overexpressed in solid tumors (STs).</p><p><strong>Objective: </strong>This open-label, multicenter phase 1b/2 study (NCT02953782) aimed to determine the recommended phase 2 dose (RP2D) and evaluate the safety, tolerability, and efficacy of magrolimab + cetuximab in patients with advanced CRC or other STs.</p><p><strong>Patients and methods: </strong>A total of 78 patients were enrolled at eight study sites in the USA. In phase 1b, patients with advanced STs received weekly maintenance doses of magrolimab at 10-45 mg/kg and cetuximab at 200-250 mg/m² following 3 + 3 dose-escalation. In phase 2, patients with anti-EGFR-refractory CRC received magrolimab + cetuximab at RP2Ds. Primary endpoints were dose-limiting toxicities, adverse events, and objective response rate (ORR; phase 2).</p><p><strong>Results: </strong>The maximum tolerated dose was not reached in phase 1b. Two RP2Ds were explored in phase 2: magrolimab at 30 or 45 mg/kg plus cetuximab at 250 mg/m². Most common treatment-related adverse events (TRAEs) were dermatitis acneiform (35.9%), infusion-related reactions (33.3%), dry skin (32.1%), fatigue (32.1%), and headache (29.5%). Most common grade ≥ 3 TRAEs were anemia (11.5%), increased blood bilirubin (9.0%), and decreased lymphocyte count (9.0%). Discontinuation of any study treatment owing to TRAEs occurred in 3.8% of patients. No deaths occurred due to TRAEs. In phase 2, ORR was 6.3% and 0% in the KRASwt and KRASmt CRC cohorts, respectively; disease control rate was 50.0% and 38.1%, and median overall survival was 9.5 and 7.6 months, respectively.</p><p><strong>Conclusions: </strong>These results indicate tolerability and potential antitumor activity when combining anti-CD47 therapy and cetuximab in heavily pretreated patients with CRC.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"519-530"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Mechanisms for Immunotherapy Resistance in Adult Soft-Tissue Sarcoma.","authors":"Zaina S Kret, Ryan J Sweder, Raphael Pollock, Gabriel Tinoco","doi":"10.1007/s11523-025-01145-5","DOIUrl":"10.1007/s11523-025-01145-5","url":null,"abstract":"<p><p>Soft-tissue sarcomas represent a diverse group of rare malignancies originating from mesenchymal tissue, accounting for less than 1% of adult cancers in the USA. With over 13,000 new cases and around 5350 deaths annually, patients with metastatic soft-tissue sarcomas face limited therapeutic options and an estimated median overall survival of 18 months. While immunotherapy has demonstrated effectiveness in several cancers, its application in soft-tissue sarcomas remains challenging owing to the tumors' largely \"cold\" immunological environment, characterized by low levels of tumor-infiltrating lymphocytes and a lack of soft-tissue sarcoma-specific biomarkers. This review examines potential mechanisms underlying immunotherapy resistance in soft-tissue sarcomas, including the complex interplay between innate and adaptive immunity, the tumor microenvironment, and the role of immune-related genes. Despite preliminary findings suggesting correlations between immune profiles and histological subtypes, consistent biomarkers for predicting immunotherapeutic responses across soft-tissue sarcoma types are absent. Emerging strategies focus on converting \"cold\" tumors to \"hot\" tumors, enhancing their susceptibility to immunologic activation. While research is ongoing, personalized treatment approaches may offer hope for overcoming the inherent heterogeneity and resistance seen in soft-tissue sarcomas, ultimately aiming to improve outcomes for affected patients.</p>","PeriodicalId":22195,"journal":{"name":"Targeted Oncology","volume":" ","pages":"485-502"},"PeriodicalIF":4.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}