Current Problems in Cancer最新文献

{"title":"Menin signaling and therapeutic targeting in breast cancer","authors":"Peng Liu ,&nbsp;Chaowen Shi ,&nbsp;Lipeng Qiu ,&nbsp;Dongsheng Shang ,&nbsp;Ziwen Lu ,&nbsp;Zhigang Tu ,&nbsp;Hanqing Liu","doi":"10.1016/j.currproblcancer.2024.101118","DOIUrl":"10.1016/j.currproblcancer.2024.101118","url":null,"abstract":"<div><p>To date, mounting evidence have shown that patients with multiple endocrine neoplasia type 1 (MEN1) may face an increased risk for breast carcinogenesis. The product of the <em>MEN</em>1 gene, menin, was also indicated to be an important regulator in breast cancer signaling network. Menin directly interacts with MLL, EZH2, JunD, NF-κB, PPARγ, VDR, Smad3, β-catenin and ERα to modulate gene transcriptions leading to cell proliferation inhibition. Moreover, interaction of menin-FANCD2 contributes to the enhancement of BRCA1-mediated DNA repair mechanism. Ectopic expression of menin causes Bax-, Bak- and Caspase-8-dependent apoptosis. However, despite numbers of menin inhibitors were exploited in other cancers, data on the usage of menin inhibitors in breast cancer treatment remain limited. In this review, we focused on the menin associated signaling pathways and gene transcription regulations, with the aim of elucidating its molecular mechanisms and of guiding the development of novel menin targeted drugs in breast cancer therapy.</p></div>","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":"51 ","pages":"Article 101118"},"PeriodicalIF":2.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538970","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":"The predictive value of hematological inflammatory markers for severe oral mucositis in patients with nasopharyngeal carcinoma during intensity-modulated radiation therapy: A retrospective cohort study","authors":"Xiaoxian Huang ,&nbsp;Xinling Qin ,&nbsp;Weimei Huang ,&nbsp;Ben Huang","doi":"10.1016/j.currproblcancer.2024.101117","DOIUrl":"10.1016/j.currproblcancer.2024.101117","url":null,"abstract":"<div><h3>Background</h3><p>This study aims to investigate the predictive value of the circulating blood cell count, including neutro-philto-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR), and thesystemic inflammation index (SII) for the development of severe oral mucositis (SOM) induced by radiation in patients undergoing radiotherapy for nasopharyngeal carcinoma (NPC).</p></div><div><h3>Methods</h3><p>In this retrospective study, 142 NPC patients were screened, and based on mucositis toxicity grade, they were categorized into two groups: SOM and nonSOM. Peripheral blood cell counts were conducted prior to Intensity-Modulated Radiation Therapy (IMRT). Associations between blood cell count, NLR, PLR, SII, and SOM occurrence were examined.</p></div><div><h3>Results</h3><p>Revealed elevated NLR and SII levels, along with reduced lymphocyte (LYM), eosinophil (EOS), and basophil (BAS) in patients with SOM. LYM, EOS, BAS, NLR, and SII were effective predictors of the severity of radiation-induced oral mucositis (RIOM) in NPC patients.</p></div><div><h3>Conclusions</h3><p>The occurrence of SOM was strongly linked to the hematological status at the start of Radiation Therapy (RT). Integrating BAS count and NLR into comprehensive risk prediction models could prove valuable for predicting SOM in NPC patients.</p></div>","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":"51 ","pages":"Article 101117"},"PeriodicalIF":2.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0147027224000588/pdfft?md5=8326ff79369479e0a1f515805be17da2&pid=1-s2.0-S0147027224000588-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141472821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current perspectives of KRAS in non-small cell lung cancer","authors":"Ethan Harris ,&nbsp;Rajat Thawani","doi":"10.1016/j.currproblcancer.2024.101106","DOIUrl":"https://doi.org/10.1016/j.currproblcancer.2024.101106","url":null,"abstract":"<div><p>NSCLC has a diverse genomic background with mutations in key proto-oncogenic drivers including Kirsten rat sarcoma (KRAS) and epidermal growth factor receptor (EGFR). Roughly 40% of adenocarcinoma harbor Kras activating mutations regardless of smoking history. Most KRAS mutations are located at G12, which include G12C (roughly 40%), G12V (roughly 20%), and G12D (roughly 15%). KRAS mutated NSCLC have higher tumor mutational burden and some have increased PD-1 expression, which has resulted in better responses to immunotherapy than other oncogenes. While initial treatment for metastatic NSCLC still relies on chemo-immunotherapy, directly targeting KRAS has proven to be efficacious in treating patients with KRAS mutated metastatic NSCLC. To date, two G12C inhibitors have been FDA-approved, namely sotorasib and adagrasib. In this review, we summarize the different drug combinations used to target KRAS G12c, upcoming G12D inhibitors and novel therapies targeting KRAS.</p></div>","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":"51 ","pages":"Article 101106"},"PeriodicalIF":2.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141328663","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":"Title Page","authors":"","doi":"10.1016/S0147-0272(24)00062-X","DOIUrl":"10.1016/S0147-0272(24)00062-X","url":null,"abstract":"","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":"51 ","pages":"Article 101121"},"PeriodicalIF":2.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141979410","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":"High-grade neuroendocrine head and neck cancer: Case series and review of the literature","authors":"Javier David Benitez Fuentes ,&nbsp;Sally Fouda ,&nbsp;Elin Evans ,&nbsp;Nachi Palaniappan ,&nbsp;Thomas Rackley ,&nbsp;Po Chan ,&nbsp;Mererid Evans ,&nbsp;Richard Webster","doi":"10.1016/j.currproblcancer.2024.101105","DOIUrl":"10.1016/j.currproblcancer.2024.101105","url":null,"abstract":"<div><h3>Background</h3><p>High-grade neuroendocrine cancers (NEC) of the head and neck (HN) are rare and aggressive, accounting for ≤1 % of all HN cancers, with a 5-year overall survival (OS) of ≤20 %. This case series examines clinical characteristics, treatments, and outcomes of patients diagnosed at a regional UK HN cancer centre over the last 23 years.</p></div><div><h3>Methods</h3><p>A retrospective review of medical records was conducted for all patients diagnosed with NEC HN from 1st January 2000 until 1st March 2023 at Velindre Cancer Centre.</p></div><div><h3>Results</h3><p>During the study period, 19 cases of NEC HN were identified, primarily affecting males (<em>n</em> = 15, 79 %). Median age of 67 years (range: 44–86). At diagnosis, 32 % of patients (<em>n</em> = 6) were smokers. The most common primary tumour sites were larynx (<em>n</em> = 5, 26.3 %) and sinonasal (<em>n</em> = 5, 26.3 %). Most patients presented with advanced loco-regional disease or distant metastasis, with stage IVA (<em>n</em> = 6, 32 %) and stage IVC (<em>n</em> = 6, 32 %) being the most common. The key pathology marker was synaptophysin, present in 100 % of the tested patients (<em>n</em> = 15). In the study, of the 12 patients with non-metastatic disease, 10 received a combination of treatments that included radiotherapy (RT). Some of these patients also received chemotherapy (CT) at the same time as their radiotherapy. Surgery alone was used in two patients with stage II disease. Seven subjects had complete responses, and one achieved a partial response. Among the seven metastatic patients, three received CT, and one underwent palliative RT, all achieving a partial response. In all cases, the CT used was carboplatin and etoposide. After a median follow-up of 11 months (range: 1–96), the median OS was 27 months for the overall population, 51 months for those treated radically, and three months for metastatic patients with palliative treatment. The 1-year OS for all patients was 54.3 %, the 2-year OS was 46.5 %, and the 5-year OS was 23.3 %. Among patients treated radically, these rates were 65.3 %, 52.2 %, and 26.1 %, respectively. For patients treated palliatively, the 1-year OS was 33.3 %.</p></div><div><h3>Conclusion</h3><p>This case series contributes preliminary observations on the characteristics and management of non-metastatic NEC HN, suggesting potential benefits from multimodality treatment strategies. Given the small cohort size, these observations should be interpreted cautiously and seen as a foundation for further research.</p></div>","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":"51 ","pages":"Article 101105"},"PeriodicalIF":2.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141187239","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":"Information for Readers","authors":"","doi":"10.1016/S0147-0272(24)00063-1","DOIUrl":"10.1016/S0147-0272(24)00063-1","url":null,"abstract":"","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":"51 ","pages":"Article 101122"},"PeriodicalIF":2.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141979411","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":"Efficacy and safety of selinexor for patients with relapsed and refractory multiple myeloma: A meta-analysis","authors":"Laila Shafei ,&nbsp;Shaima Bashir ,&nbsp;Esther W. Chan ,&nbsp;Dina Abushanab ,&nbsp;Anas Hamad ,&nbsp;Daoud Al-Badriyeh","doi":"10.1016/j.currproblcancer.2024.101076","DOIUrl":"https://doi.org/10.1016/j.currproblcancer.2024.101076","url":null,"abstract":"<div><h3>Purpose</h3><p>Selinexor is a first-in-class, oral selective-inhibitor-of-nuclear-export, granted accelerated approval by FDA (2019) for relapsed and refractory multiple myeloma (RRMM). We sought to quantitatively summarize the selinexor efficacy and safety in RRMM.</p></div><div><h3>Methods</h3><p>We searched PubMed, EMBASE, CENTRAL, clinicaltrial.gov, and google scholar, until May 2023, studies about selinexor use in RRMM. The outcome measures of interest were primarily efficacy outcomes, in addition to safety outcomes. Random-effect model analyses were performed, at statistical significance of P&lt;0.05, using the RevMan software.</p></div><div><h3>Results</h3><p>Meta-analyses of eleven included clinical trials yielded a significant 56.21% overall clinical benefit, 46.91% overall response, 4.89% complete response, 23.41% very good partial response, 24.68% partial response, and 28.06% stable disease rates with selinexor. Due to safety reasons, selinexor caused significant increase in discontinuation rate, 16.80%. Subgroup analyses demonstrated higher efficacy with selinexor plus dexamethasone and proteasome inhibitor combinations than with selinexor alone. The multiple myeloma type, high cytogenetic risk, refractory state, and advanced disease state did not affect performance. Risk of selection, performance, and detection biases were unclear in the included trials.</p></div><div><h3>Conclusion</h3><p>Selinexor led to significant positive responses with an acceptable safety profile in RRMM patients, despite higher rates of safety-related discontinuations. Selinexor-based combinations further enhanced response.</p></div>","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":"50 ","pages":"Article 101076"},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140296641","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":"Comparative effectiveness of lenalidomide/dexamethasone-based triplet regimens for treatment of relapsed and/or refractory multiple myeloma in the United States: An analysis of real-world electronic health records data","authors":"Sikander Ailawadhi ,&nbsp;Mu Cheng ,&nbsp;Dasha Cherepanov ,&nbsp;Maral DerSarkissian ,&nbsp;Dawn Marie Stull ,&nbsp;Annalise Hilts ,&nbsp;Justin Chun ,&nbsp;Mei Sheng Duh ,&nbsp;Larysa Sanchez","doi":"10.1016/j.currproblcancer.2024.101078","DOIUrl":"https://doi.org/10.1016/j.currproblcancer.2024.101078","url":null,"abstract":"<div><h3>Background</h3><p>This retrospective longitudinal study compared the effectiveness of dexamethasone+lenalidomide (Rd)-based triplet regimens containing proteasome inhibitors (PIs) ixazomib (IRd), carfilzomib (KRd), and bortezomib (VRd) or monoclonal antibodies (MABs) elotuzumab (ERd) and daratumumab (DRd) in patients with relapsed/refractory multiple myeloma (RRMM)—including those with high cytogenetic risk—primarily treated at community oncology clinics in the United States.</p></div><div><h3>Methods</h3><p>Electronic health records of adult RRMM patients in a deidentified real-world database (01/01/2014–09/30/2020) who initiated IRd, KRd, VRd, ERd, or DRd in the second or later line of therapy (LOT) were analyzed. The index date was the date of initiation of each LOT and baseline was the 6-month pre-index period. Duration of therapy (DOT), time to next therapy (TTNT), progression-free survival (PFS), and overall survival (OS) were compared across regimens with multivariable Cox proportional hazards models.</p></div><div><h3>Results</h3><p>Of the 1,185 patients contributing 1,332 LOTs, 985 had standard cytogenetic risk (median age, 71 years) and 180 had high risk (median age, 69 years). Compared with other regimens, DRd was associated with longer DOT overall (adjusted hazard ratio [95 % confidence interval]: 1.84 [1.42, 2.38] vs. KRd, 1.65 [1.20, 2.28] vs. ERd, 1.58 [1.23, 2.04] vs. IRd, and 1.54 [1.18, 2.00] vs. VRd), and longer TTNT and PFS. KRd was associated with shorter OS compared with DRd (1.45 [1.01, 2.08]) and VRd (1.32 [1.01, 1.73]). High-risk patients had similar outcomes with all triplet regimens.</p></div><div><h3>Conclusion</h3><p>Although DRd improved clinical outcomes overall, Rd-based triplet regimens containing a PI or MAB are similarly effective in high-risk RRMM.</p></div>","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":"50 ","pages":"Article 101078"},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308720","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":"Primary and secondary prevention of cervical cancer among Italian AFAB transgender people","authors":"Alessandra Lami ,&nbsp;Stefania Alvisi ,&nbsp;Arianna Siconolfi ,&nbsp;Renato Seracchioli ,&nbsp;Maria Cristina Meriggiola","doi":"10.1016/j.currproblcancer.2024.101103","DOIUrl":"https://doi.org/10.1016/j.currproblcancer.2024.101103","url":null,"abstract":"<div><h3>Objective</h3><p>Currently, available data on preventive measures for Human Papillomavirus (HPV) infection and cervical cancer in the transgender assigned female at birth (AFAB) community are extremely limited. Our aim was to analyze adherence to primary and secondary cervical cancer prevention screening programs among transgender AFAB people attending our gender clinic.</p></div><div><h3>Methods</h3><p>Transgender AFAB people attending our center were recruited. Anamnestic data were collected for each person through completion of a medical history form and medical records. Variables recorded included previous HPV vaccination, adherence to regional screening programs (Pap smear or HPV DNA test), subject age, duration of current or prior gender-affirming hormone therapy (GAHT) and whether gender affirmation surgery (GAS) with hysterectomy had been performed. Open questions regarding reasons for not undergoing screening tests were also included.</p></div><div><h3>Results</h3><p>In this cross-sectional study, 263 AFAB transgender people were included, with a mean age of 30.6 ± 10.5 years. GAS with hysterectomy had been performed on 37.6 % of these people. Of our participants, 71.7 % who were born after 1998 (the first cohort to receive HPV vaccination invitations in Italy) had been vaccinated for HPV. Seventy-four-point-nine percent of participants who were still eligible for cervical screening had never undergone Pap smear or HPV DNA testing, whereas those who had undergone at least one cervical screening had done so on average 4.2 ± 4.5 years ago.</p></div><div><h3>Conclusion</h3><p>HPV vaccination prevalence in the AFAB transgender population born after 1998 is in line with the Italian AFAB general population. However, adherence to cervical cancer screening programs in the transgender AFAB population appears to be lower in comparison to the cisgender population. Further efforts are required from the medical community to enhance AFAB transgender people's adherence to HPV vaccination and to cervical screening.</p></div>","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":"50 ","pages":"Article 101103"},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140913943","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":"Borderline tumours of ovary and fertility preservation–Outcomes from a tertiary care center in India","authors":"Sarita Kumari ,&nbsp;Neerja Bhatla ,&nbsp;Chandrima Ray ,&nbsp;Bhawna Arora ,&nbsp;Sandeep Mathur ,&nbsp;Sunesh Kumar ,&nbsp;Lalit Kumar","doi":"10.1016/j.currproblcancer.2024.101097","DOIUrl":"https://doi.org/10.1016/j.currproblcancer.2024.101097","url":null,"abstract":"<div><h3>Objective</h3><p>Borderline ovarian tumors (BOT) are characterized by atypical epithelial proliferation without stromal invasion and majority are diagnosed in women of reproductive age group desirous of fertility preservation.</p></div><div><h3>Methods</h3><p>A retrospective review of medical records of patients diagnosed with BOT and on regular follow up at the All India Institute of Medical Sciences New Delhi, during a nine-year study period from March 2014 to March 2023 was performed. Surgical treatment was classified as radical or fertility sparing surgery (FSS). Surgical staging was defined as complete, partial or un-staged.</p></div><div><h3>Results</h3><p>Median age of 91 women was 34 years. Follow up period ranged from 4 to 222 months (median 77 months). Among 68 premenopausal women, 31 (46 %) underwent radical surgery and FSS in 37 (54 %) cases. Median time to conception in 29 women with future fertility wishes was 13 months (range, 4 to38 m). Seven of 29 cases (29 %) required ovulation induction. The pregnancy rate was 82.7 % and live birth rate was 80 %. Eight cases (8.7 %) had a recurrence (7- un-staged, 1- partially staged) and median time to recur was 36 months. There was no significant difference in recurrence between cystectomy/oophorectomy. Ovary was the site of recurrence in all surgically salvaged cases except peritoneal cavity in 1 case with mortality. Relapse free survival at 5 and 10 years in FSS and radical surgery group were similar.</p></div><div><h3>Conclusion</h3><p>FSS is a safe procedure and should be considered in young patients desirous of future fertility along with a comprehensive peritoneal staging. Reproductive outcomes are excellent.</p></div>","PeriodicalId":55193,"journal":{"name":"Current Problems in Cancer","volume":"50 ","pages":"Article 101097"},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140535546","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}