Cancer research communications最新文献

{"title":"Phase 1b study of immunocytokine simlukafusp alfa (FAP-IL2v) combined with pembrolizumab for treatment of advanced and/or metastatic melanoma.","authors":"Eva Munoz-Couselo, Ainara Soria Rivas, Shahneen Sandhu, Georgina V Long, Miguel F Sanmamed, Anna Spreafico, Elizabeth Buchbinder, Mario Sznol, Hans Prenen, Alexander Fedenko, Mohammed Milhem, Ana Maria Arance Fernandez, Jean-Jacques Grob, Lev Demidov, Caroline Robert, Christin Habigt, Stefan Evers, Nassim Sleiman, David Dejardin, Caroline Ardeshir, Nicole Martin, Christophe Boetsch, Jehad Charo, Volker Teichgraeber, Anton Kraxner, Nino Keshelava, Oliver Bechter","doi":"10.1158/2767-9764.CRC-24-0601","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-24-0601","url":null,"abstract":"<p><strong>Purpose: </strong>This study explored the combination of FAP-IL2v, a novel immune-cytokine, with pembrolizumab in patients with advanced and/or metastatic melanoma.</p><p><strong>Patients and methods: </strong>This open-label, multicenter, phase 1b clinical study (NCT03875079) evaluated the safety, tolerability, pharmacodynamics, pharmacokinetics (PK), and antitumor activity of FAP-IL2v (simlukafusp alfa, RO6874281) in combination with pembrolizumab. Patients with advanced and/or metastatic melanoma were either checkpoint inhibitor (CPI)-naïve or -experienced. Patients received 10 mg FAP-IL2v either continuously once every three weeks (Q3W) or in an induction/maintenance setting consisting of a 3-week induction phase with weekly (QW) dosing followed by continuous Q3W dosing. Pembrolizumab was dosed Q3W at 200 mg.</p><p><strong>Results: </strong>Eighty-three patients were treated, 16 patients in two safety run-in cohorts, and 67 patients in two extension cohorts; 75 (90.4%) patients were CPI-experienced. The PK of FAP-IL2v in combination with pembrolizumab was similar to that after administration as monotherapy. Consistent with the proposed mode-of-action, FAP-IL2v preferentially expanded NK and CD8 T cells. The most common FAP-IL2v-related grade 3/4 AEs were lymphopenia (23%), elevated γ‑glutamyltransferase (8%), elevated alanine aminotransferase (6%), and infusion-related reaction (6%). A response was observed in 5 of 75 (6.7%) CPI-experienced patients (all partial responses) and in 2 of 8 CPI-naïve patients (one complete, one partial response). The median progression-free survival was 3.1 months.</p><p><strong>Conclusions: </strong>The safety profile of FAP-IL2v in combination with pembrolizumab was manageable and consistent with the known safety profile. However, further exploration of FAP-IL2v and pembrolizumab was precluded in melanoma patients with prior CPI due to the lack of clinical activity.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ternary Complex Components Responsible for Rapid LDL Internalization as Biomarkers for Breast Cancer Associated with Proliferation and Early Recurrence.","authors":"Elizabeth S McDonald, Tien-Chi Pan, Dhruv K Pant, Melissa A Troester, Andrew V Kossenkov, David A Mankoff, Robert H Mach, Lewis A Chodosh","doi":"10.1158/2767-9764.CRC-23-0562","DOIUrl":"10.1158/2767-9764.CRC-23-0562","url":null,"abstract":"<p><strong>Significance: </strong>This first large-scale analysis of the putative ternary complex responsible for rapid low-density lipoprotein internalization in breast cancer reveals a link between component expression and recurrence, with prognostic implications for identifying patients needing supplemental posttreatment surveillance and/or additional therapeutic approaches.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"226-239"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of NF1 Accelerates Uveal and Intradermal Melanoma Tumorigenesis, and Oncogenic GNAQ Transforms Schwann Cells.","authors":"Anne Nathalie Longakit, Oscar Urtatiz, Amy Luty, Christina Zhang, Chloe Hess, Alyssa Yoo, Hannah Bourget, Catherine D Van Raamsdonk","doi":"10.1158/2767-9764.CRC-24-0386","DOIUrl":"10.1158/2767-9764.CRC-24-0386","url":null,"abstract":"<p><strong>Significance: </strong>These results indicate that NF1 loss in intradermal and uveal melanomas is a potentially significant finding. They emphasize the importance of neurofibromin in cAMP signaling. They show for the first time that oncogenic GNAQ can transform Schwann cells in mice. The Plp1-creERT transgene with tamoxifen given at 5 weeks may be a particularly good strategy for modeling cutaneous neurofibroma and plexiform neurofibroma.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"209-225"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic tracking of tumor microenvironment modulation using Kaede photoconvertible transgenic mice unveils new biological properties of viral immunotherapy.","authors":"Anne R Diers, Qiuchen Guo, Zhi Li, Erin Richardson, Suaad Idris, Claire Willis, Paul P Tak, David R Withers, Francesca Barone","doi":"10.1158/2767-9764.CRC-24-0434","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-24-0434","url":null,"abstract":"<p><p>CAN-2409 is a replication-defective adenovirus that delivers the herpes simplex virus (HSV)-thymidine kinase gene to infected cells. Intratumoral administration of CAN-2409 followed by prodrug results in the formation of a toxic metabolite able to induce immunogenic cell death, exposure of tumor-associated antigens, and activation of local and systemic immune responses. We used a dynamic labeling model with MC38 tumor cells implanted in photoconvertible Kaede mice. Violet light was used to label the tumor microenvironment, distinguishing retained versus newly entering cells and allowing real-time monitoring of immune compartment changes within tumors. Administration of CAN-2409 + prodrug led to control of tumor growth and a significantly increased effector CD8+ T cell responses. Photolabeling of the tumor microenvironment (TME) revealed that rather than enhancing recruitment of T cells to the tumor, CAN-2409 altered the TME whereby newly entering and retained CD8+ T cells were significantly more proliferative. CAN-2409 supported reinvigoration of tumor associated antigen-specific CD8+ T cells and expansion of Tregs of an altered phenotype. Moreover, the combination of CAN-2409 + prodrug and anti-CTLA-4 antibody treatment further improved control of tumor growth, in part by the enhanced CD8+ T cell-mediated effector function and diminished Treg-mediated immunosuppression. Collectively, these data defined at least two temporally distinct pathways underpinning the mechanism of action of CAN-2409 action that overcome cell exhaustion and decreases immune suppression. The results also support the rationale for future clinical trials of CAN-2409 treatment combined with anti-CTLA-4 antibody therapy.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression Patterns of DLL3 Across Neuroendocrine and Non-Neuroendocrine Neoplasms Reveal Broad Opportunities for Therapeutic Targeting.","authors":"John R Lozada, Andrew Elliott, Mark G Evans, James Wacker, Kathleen M Storey, Emily A Egusa, Nicholas A Zorko, Akhilesh Kumar, Anthony Crymes, Elisabeth I Heath, Benedito A Carneiro, Heloisa P Soares, Frank Cichocki, Jeffrey S Miller, Emil Lou, Himisha Beltran, Emmanuel S Antonarakis, Charles J Ryan, Justin H Hwang","doi":"10.1158/2767-9764.CRC-24-0501","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-24-0501","url":null,"abstract":"<p><p>Neuroendocrine neoplasms (NENs) encompass a diverse set of malignancies with limited precision therapy options. Recently, therapies targeting DLL3 have shown clinical efficacy in aggressive NENs, including small cell lung cancers and neuroendocrine prostate cancers. Given the continued development and expansion of DLL3-targeted therapies, we sought to characterize the expression of DLL3 and identify its clinical and molecular correlates across diverse neuroendocrine and non-neuroendocrine cancers. Here, we interrogated paired DNA and RNA-sequencing from 1,589 NENs across 29 sites, as well as 203,252 tumors across 47 cancer types. We found that high transcriptomic levels of DLL3 correlated with more aggressive histologic and mutational patterns in NENs, with adverse survival outcomes being reflected in NENs originating from the lung, pancreas, stomach, and small bowel. The heterogeneity in DLL3 expression across NENs was largely explained by site of origin, with lung, prostate, and bladder NENs exhibiting relatively high levels of DLL3 whereas gastroenteropancreatic (GEP) NENs displayed relatively low expression levels. Although the therapeutic targeting of DLL3 may be less applicable for GEP-NENs, we did find an upregulation of alternative targets such as SEZ6, CELSR3, and SSTR2 in these settings. Lastly, expanding our investigation into non-neuroendocrine cancers, we detected an enrichment of DLL3 in both low-grade and high-grade gliomas, Merkel cell carcinomas, medulloblastomas, and melanomas, with such enrichment being associated with prolonged overall survival in gliomas, but worse overall survival in melanomas. Altogether, we demonstrate that DLL3 represents an attractive target for subsets of neuroendocrine and non-neuroendocrine cancers and uncover opportunities for future therapeutic strategies.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PARP inhibitors differentially regulate immune responses in distinct genetic backgrounds of high-grade serous tubo-ovarian carcinoma models.","authors":"Luiza Doro Pereira, Monica Wielgos-Bonvallet, Selim Misirlioglu, Alireza Khodadadi-Jamayran, Petar Jelinic, Douglas A Levine","doi":"10.1158/2767-9764.CRC-24-0515","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-24-0515","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have revolutionized treatment for several tumor indications without demonstrated benefit for ovarian cancer patients. To improve the therapeutic ratio of ICIs in ovarian cancer patients, several different clinical trials are testing combinations with poly (ADP-ribose) polymerase (PARP) inhibitors. Comparing the immunomodulatory effects of clinically advanced PARP inhibitors may help to identify the best partner to combine with ICIs. We examined the treatment effect of talazoparib (a PARP trapper) and veliparib (a solely PARP enzymatic inhibitor) in homologous recombination deficient (HRD) and homologous recombination proficient (HRP) high-grade serous tubo-ovarian carcinoma (HGSC) cell lines on immune-related gene expression. We discovered and validated that CXCL8, IL-6, and TNF gene expression were upregulated after talazoparib treatment in both OVCAR3 (HRD) and CAOV3 (HRP) HGSC cell lines. In contrast, veliparib treatment slightly elevated similar genes exclusively in a HRD HGSC cell line model. We expanded these studies to include olaparib, a PARP trapper less potent than talazoparib, and found effects specific to COV361 (BRCA1 mutant) and OVCAR8 (BRCA1 methylated) HGSC cells but not all HRD HGSC cell lines. Our studies also identified differences among PARP trappers versus veliparib on augmenting CXCL10 expression. Finally, we show that talazoparib modulates the CXCL10 response in cGAS-defective cell lines, independent of the cGAS-STING pathway. These mechanistic studies advance our understanding of how different PARP inhibitors affect the immune system in various genetic backgrounds.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a microvessel density gene signature and its application in precision medicine.","authors":"Megumi Kuronishi, Yoichi Ozawa, Takayuki Kimura, Shuyu Dan Li, Yu Kato","doi":"10.1158/2767-9764.CRC-24-0403","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-24-0403","url":null,"abstract":"<p><p>Combination therapy with anti-angiogenic drugs and immune checkpoint inhibitors has shown enhanced clinical activity and has been approved for the treatment of multiple tumor types. Despite extensive research, predictive biomarkers for combination therapy remain poorly understood. Microvessel density (MVD), a surrogate marker for aberrant angiogenesis measured by immunohistochemistry (IHC), has been associated with response to monotherapy with anti-angiogenesis inhibitors. However, obtaining tumor tissue with a sufficient mass for IHC analysis is not always practical, and IHC-based MVD measurements are unavailable in large public datasets. In this study, we developed an MVD gene score based on RNA-sequencing data that reflects MVD by using RNA-seq and MVD measured by IHC in 12 mouse syngeneic tumor models. We explored the relationship between the MVD gene score and a gene signature predicting the response to anti-PD-1 therapy in mouse and human tumor datasets. The MVD gene score correlated with the antitumor activity of lenvatinib, a multiple tyrosine kinase inhibitor mainly targeting VEGFRs and FGFRs, in mouse tumor models and MVD measured by IHC in commercially available human formalin-fixed, paraffin-embedded tumor samples. Tumor types in The Cancer Genome Atlas were classified into four subgroups based on the MVD gene score and T-cell inflamed gene expression profile (TcellinfGEP), which were correlated with clinical indications for treatment. In conclusion, the newly developed MVD gene score enables the estimation of MVD in large public datasets where IHC data are unavailable and has potential clinical utility together with the TcellinfGEP to characterize patients' tumors for precision medicine.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age at first full-term pregnancy and other reproductive factors are associated with mammographic breast density in postmenopausal women: a study in Flanders, Belgium.","authors":"Magda J Vandeloo, Eliane Kellen, Carolyn Y Fang, Eric A Ross, Liesbeth Vancoillie, Liesbeth M Bruckers, Kristof Y Neven, Esmée M Bijnens, Tim S Nawrot, Chantal Van Ongeval","doi":"10.1158/2767-9764.CRC-24-0561","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-24-0561","url":null,"abstract":"<p><p>This study evaluated the association between age at first full-term pregnancy (FFTP) and mammographic breast density (MBD) in postmenopausal women. 1,034 women, age 50-69y, were recruited from the Flemish (Belgium) population-based breast cancer screening program. Participants completed a questionnaire on lifestyle and reproductive factors. From mammography we assessed the percentage glandular tissue of the total breast volume (GLAND), the Volumetric Breast Density (VBD), and the BI-RADS density classification. For statistical analysis we used the piecewise linear regression (PLR) model. Average age at FFTP was 26.1 years. Among women with a FFTP >25.7 years, each year increase in FFTP was associated with 1.17% increase in GLAND (95%CI: 0.20% to 2.46%, p = 0.041) and 1.45% increase in VBD (95%CI: 0.18% to 2.75%, p = 0.026). Similarly, the odds of a higher BI-RADS classification increased by 5.0% (95%CI: 0.0% to 11.0%, p = 0.059) for each year increase in FFTP age after 25.7 years. For every year delay in age at menarche, there was a 2.48% higher GLAND (95%CI: 0.43 % to 4.57%, p = 0.017) and 2.45% higher VBD (95%CI: 0.38 % to 4.56%, p = <0.020). Ever use of oral contraceptive resulted in 12.24% lower in GLAND (95%CI: -20.90% to -2.63%, p = 0.014) and 13.48% lower in VBD (95%CI:-22.1% to -3.91%, p = 0.007). MBD is significantly higher when FFTP takes place after 25.7 years. Later age at menarche is associated with higher MBD, while ever use of oral contraceptive was associated with lower MBD at postmenopause.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A melanoma brain metastasis CTC signature and CTC:B cell clusters associate with secondary liver metastasis: a melanoma brain-liver metastasis axis.","authors":"Tetiana Y Bowley, Mireya C Ortiz, Irina V Lagutina, Mara P Steinkamp, Bridget N Fahy, Bernard Tawfik, Moises Harari-Turquie, Dario Marchetti","doi":"10.1158/2767-9764.CRC-24-0498","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-24-0498","url":null,"abstract":"<p><p>Melanoma brain metastasis (MBM) is linked to dismal prognosis, low overall survival, and is detected in up to 80% of patients at autopsy. Circulating tumor cells (CTCs) are the smallest functional units of cancer and precursors of fatal metastasis. We previously employed an unbiased multilevel approach to discover a unique ribosomal protein large/small subunits (RPL/RPS) CTC gene signature associated with MBM. Here, we hypothesized that CTC-driven MBM secondary metastasis (\"metastasis of metastasis\" per clinical scenarios), has targeted organ specificity for liver. We injected parallel cohorts of immunodeficient and newly-developed humanized NBSGW (HuNBSGW) mice with cells from CTC-derived MBM to identify secondary metastatic patterns. We found the presence of a melanoma brain-liver metastasis axis in humanized NBSGW mice. Further, RNA-Seq analyses of tissues showed a significant upregulation of the RPL/RPS CTC gene signature linked to metastatic spread to liver. Additional RNA-Seq of CTCs from HuNBSGW blood revealed extensive CTC clustering with human B cells in these mice. CTC:B cell clusters were also upregulated in blood of primary melanoma patients, and maintained either in CTC-driven MBM or MBM CTC-derived cells promoting liver metastasis. CTC-generated tumor tissues were interrogated at single-cell gene and protein expression levels (10x Genomics Xenium and HALO spatial biology platforms, respectively). Collectively, our findings suggest that heterotypic CTC:B cell interactions can be critical at multiple stages of metastasis.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MYC and HSF1 Cooperate to Drive Sensitivity to Polo-like Kinase 1 Inhibitor Volasertib in High Grade Serous Ovarian Cancer.","authors":"Imade Williams, Matthew O'Malley, Haddie DeHart, Bobby Walker, Vrushabh Ulhaskumar, Pranav Jothirajah, Haimanti Ray, Lisa M Landrum, Joe R Delaney, Kenneth P Nephew, Richard L Carpenter","doi":"10.1158/2767-9764.CRC-24-0400","DOIUrl":"10.1158/2767-9764.CRC-24-0400","url":null,"abstract":"<p><p>Ovarian cancer is a deadly gynecological disease with frequent recurrence. Current treatments for patients include platinum-based therapy regimens with PARP inhibitors specific for HR-deficient high-grade serous ovarian cancers (HGSOCs). Despite initial effectiveness, patients inevitably develop disease progression as tumor cells acquire resistance. Toward the development of new therapeutic avenues, we describe a gene amplification involving both HSF1 and MYC, wherein these two genes are co-amplified in over 30% of HGSCO patients. We further found that HSF1 and MYC transcriptional activity was highly correlated in human HGSOC tumors and cell lines, suggesting they may cooperate in the disease. CUT&RUN for HSF1 and MYC revealed overlapping HSF1 and MYC binding throughout the genome. Moreover, binding peaks of both transcription factors in HGSOC cells were nearly identical, and a protein-protein interaction between HSF1 and MYC was detected, supporting molecular cooperation. Supporting a functional cooperation of these two transcription factors, growth of HGSOC cells with the co-amplification was dependent on both HSF1 and MYC. To identify a therapeutic target that could take advantage of this unique HSF1 and MYC dependency, polo-like kinase 1 (PLK1) was correlated with HSF1 and MYC in HGSOC specimens. Targeting PLK1 with volasertib revealed a greater than 200-fold increased potency in HSF1-MYC co-amplified HGSOC cells compared to those with wild-type HSF1 and MYC copy number. Although the success of volasertib and other PLK1 inhibitors in clinical trials has been modest, the current study suggests that targeting PLK1 in a precision medicine approach using HSF1-MYC co-amplification as a biomarker in HGSOC.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}