Current Problems in Cancer最新文献

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.

Head and Neck Squamous Cell Carcinoma (HNSCC) is a highly heterogeneous cancer that is characterized by distinct phenotypes based on anatomical site and etiological agents. Recently, the intratumor microbiome has been implicated in cancer pathogenesis and progression. Although it is well established that the gut microbiome varies with geographical location and is highly influenced by factors such as diet, environment, and genetics, the intratumor microbiome is not very well characterized. In this review, we aim to characterize the HNSCC intratumor microbiome by geographical location and anatomical site. We conducted a review of primary literature from PubMed and assessed studies based on relevancy and recency. To the best of our knowledge, we are the first to comprehensively examine the tumor microenvironment of HNSCC with respect to these two primary factors on a large scale. Our results suggest that there are unique bacterial and fungal biomarkers for HNSCC for each of the following geographical locations: North America, Asia, Europe, Australia, and Africa. We also identified a panel of microbial biomarkers that are unique to two primary HNSCC anatomic sites, as well as microbial biomarkers associated with various etiological agents of HNSCC. Future study of these microbes may improve HNSCC diagnostic and therapeutic modalities by accounting for differences based on geographic regions and anatomical sites.

Background

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.

Methods

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.

Results

During the study period, 19 cases of NEC HN were identified, primarily affecting males (n = 15, 79 %). Median age of 67 years (range: 44–86). At diagnosis, 32 % of patients (n = 6) were smokers. The most common primary tumour sites were larynx (n = 5, 26.3 %) and sinonasal (n = 5, 26.3 %). Most patients presented with advanced loco-regional disease or distant metastasis, with stage IVA (n = 6, 32 %) and stage IVC (n = 6, 32 %) being the most common. The key pathology marker was synaptophysin, present in 100 % of the tested patients (n = 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 %.

Conclusion

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.

Objective

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.

Methods

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.

Results

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.

Conclusion

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.

Loss of human epidermal growth factor receptor 2 (HER2) expression can be seen in almost 25–30 % patients after HER2 receptor directed neoadjuvant treatment. These patients have unclear clinical outcomes in previous studies. We aimed to investigate the importance of HER2 loss, additionally with predictive factors for the loss of HER2. This was a retrospective and multicenter study that included 272 HER2-positive BC patients with no pathological complete response who received neoadjuvant chemotherapy plus HER2-targeted treatments. The factors that may affect the loss of HER2 detected by immunohistochemistry(IHC) and the association with survival were analyzed.The rate of HER2 loss after neoadjuvant treatments(NAT) was 27.9 % (n = 76). Disease recurrence was observed in 18(23.7 %) patients with HER2 loss, while it was detected in 62 (31.7 %) patients without HER2 loss(p = 0.23). Pre and post-NAT ER status, and post-NAT ki-67 status had a significant impact on disease-free survival(DFS) (p = 0.0012, p = 0.004, and p = 0.04, respectively).There were no significant association between DFS and loss of HER2 (p = 0.64) and dual anti-HER2 blockade (p = 0.21). Pre-NAT clinical stage (HR:1.65 p = 0.013), post-NAT LN status (HR:3.18, p = 0.02) and pre-NAT ER status (HR:0.24, p = 0.041) were significant independent prognostic factors for DFS while post-NAT residual disease in axillar tissue was an independent prognostic factor for OS (HR:1.54 p = 0.019). Moreover, age (<40 years vs ≥40 years) (p = 0.031) and tumor grade (p = 0.004) were predictive factors for HER2 loss. Our results showed that HER2 loss did not affect survivals. However, young age and being high grade tumor may predict HER2 loss.

Objective

In this study, we examined the relationship between the Systemic Inflammatory Response Index (SIRI) and the overall prognosis of patients with late-stage lung adenocarcinoma who harbor epidermal growth factor receptor (EGFR) mutations and are undergoing first-line treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs).

Methods

A cohort comprising 52 patients with late-stage lung adenocarcinoma, who received treatment at Jinzhou Central Hospital between January 2018 and December 2022, were carefully selected. Patient data spanning from pre-treatment assessments through follow-up periods were meticulously collected from electronic medical records and subsequently subjected to a comprehensive retrospective analysis. The collected data was subjected to in-depth processing and analyzed using SPSS 27.0 statistical software. To determine the optimal cut-off value of the pre-treatment SIRI, a receiver operating characteristic (ROC) curve was employed. Survival analysis was performed using the Kaplan-Meier method, and both univariate and multivariate prognostic analyses were conducted using Cox regression.

Results

The optimal SIRI cut-off value was determined to be 1.659 (with a specificity of 0.964 and sensitivity of 0.652, P = 0.000). Based on this value, patients were categorized into high and low SIRI groups. Chi-squared tests demonstrated that SIRI exhibited statistically significant correlations with patient age and smoking history (P < 0.05). Survival analysis revealed that the group with a lower SIRI had a significantly extended progression-free survival (PFS) (P < 0.001). Cox univariate analysis identified hypertension, pleural metastasis, liver metastasis, and SIRI as factors associated with PFS (P < 0.05). In the subsequent multivariate analysis, liver metastasis and SIRI ≥ 1.659 (P < 0.001) were identified as independent risk factors for patients.

Conclusion

Pre-treatment SIRI holds predictive significance for the prognosis of patients with late-stage lung adenocarcinoma with EGFR mutations undergoing first-line treatment EGFR-TKI treatment.

Genetic testing is an integral part of the workup of metastatic prostate cancer, in part, because the results can have a profound impact on the subsequent management of this disease. There are now several Food & Drug Administration (FDA) approved therapeutics available for patients with prostate cancer and certain genetic abnormalities – most notably, mutations in DNA damage repair (DDR) pathways such mismatch repair (MMR) and homologous recombination repair (HRR). In this review of the current literature, we discuss the indications for somatic and germline testing, the genetic changes of particular clinical relevance, the associated therapeutic options, and the clinical data supporting their use. We also highlight select trials-in-progress and future directions for the field

Objective

DNA repair genes and their variants have been found to alter the risk of oral cancer.

Method

The level of expression of XRCC3, NBS1, and OGG1 genes among 20 cases of oral cancer, 6 pre-oral cancer, and 50 healthy control subjects was measured with RT-PCR. All the subjects were also genotyped for XRCC3 rs861539 C>T, NBS1 rs1805794 C>G, and OGG1 rs1052133 C>G polymorphisms by the PCR-RFLP method; their genotypes were correlated with their level of expression. Further, a localized fold structure analysis of the mRNA sequence surrounding the studied SNPs was performed with RNAfold.

Results

Results showed increased expression of XRCC3, NBS1, and OGG1 transcripts among oral cancer (4.49 fold, 3.45 fold, and 3.27 fold) as well as pre-oral cancer (3.04 fold, 5.32 fold, and 1.74 fold) as compared to control subjects. The transcript level of OGG1 was found to be significantly increased (6.68 fold, p-value 0.009) with the GG genotype compared to the CC genotype. The C>T polymorphism of XRCC3 and the C>G polymorphism of OGG1 result in an apparent change in its mRNA secondary structure. Folding energy with the C allele for XRCC3 C>T polymorphism was lower than that of the T allele (MFE C vs T: -50.20 kcal/mol vs -48.70 kcal/mol). In the case of OGG1 C>G polymorphism MFE for the C allele was higher (-23.30 kcal/mole) than with the G allele (-24.80 kcal/mol).

Conclusion

Our results showed elevated levels of XRCC3, NBS1, and OGG1 both in oral cancer and pre-oral cancer conditions, which indicates their role as prospective biomarkers of oral cancer and pre-cancerous lesions. SNPs in these genes alter their level of expression, possibly by altering the secondary structure of their transcript. However, due to the small sample size our study can only provide a suggestive conclusion and warned future study with large sample size to verify our findings.