TMB-H

Key mutational alterations in PSCC, including high TMB and TP53 mutations, have significant implications for early diagnosis and personalized therapies. These findings support the potential use of specific genetic markers to guide targeted therapeutic approaches.

Subsequently, differential gene expression was validated in multiple LUAD cell lines using RT-qPCR. In conclusion, the risk assessment model based on nine PCIGs may be used to predict the prognosis and drug selection in patients with LUAD.

Western blotting assay revealed that inhibiting LINC01011 induced apoptosis and simultaneously inhibited epithelial-mesenchymal transition. These findings confirm the validity of the prognostic model and indicate that LINC01011 could serve as a potential research target.

A longer median overall survival (OS) was observed in mUM patients with higher expression of LAG3, HLA class I, or HLA class II; which may represent a small proportion of immune hot tumors. Expression patterns of G2M checkpoint and E2F targets suggest a possible contribution to immunotherapy response.

This aids in the detection of high-risk lesions that need a more detailed work-up and more stringent follow-up, and those that will follow a benign course. Larger studies are needed to validate the clinical utility and broader applicability.

Patients with low WT1 expression had an overall survival (OS) that was superimposable to the OS expected in MR AML. Low WT1 expression in AML is associated with a distinct and complex mutational profile, marked by frequent CHIP and MR mutations.

Monitoring these circulating peripheral blood markers in wider population of patients receiving ICI therapy, during its course, may provide a perspective in the development of new biomarkers for predicting response and may serve as a basis for personalized treatment. This case report describes valuable insights into evolution of immune markers predicting and monitoring response to Nivolumab in a patient with cancer.

This study provides new insights into prognostic prediction and immunotherapy for STAD from the perspective of the inflammatory response.

SCC of the vulva and vagina is expected to have high TMB, and gene alteration status differed between TMB-high and non-TMB-high groups.

These findings reveal promising biomarkers and mechanistic insights, offering a new perspective on predicting ICI response and opening up exciting possibilities for more personalized immunotherapy strategies in NSCLC and MIBC.

Biomarkers for ICI response/resistance include microsatellite instability, high tumor mutational burden, and PD-L1 immunohistochemistry positivity; but they are imperfect, perhaps because of immune system complexity. Herein, we explore the good, the bad, and the ugly of ICIs in cancer treatment.

Furthermore, SKCM-P8 demonstrated super-predictive accuracy compared to six published models. Overall, SKCM-P8 offers a promising tool for predicting prognosis and guiding therapeutic decisions in SKCM.

The initial treatment regimen included carboplatin, etoposide, and durvalumab. After four courses of cisplatin and irinotecan therapy, pembrolizumab was introduced, and a complete response (CR) was maintained for 18 months. We report a rare case of a long-term response to pembrolizumab in ED-SCLC with TMB-high, highlighting the potential for targeted immunotherapy in such cases.

Here, we present a systems framework for identifying immuno-oncotargets, based on analysis of gene regulatory networks, and validating the effect of these targets in transforming immune-desert into immune-inflamed tumors. In particular, we identify DEAD-box helicases 54 (DDX54) as a master regulator of immune escape in immune-desert lung cancer with TMB-H and show that knockdown of DDX54 can increase immune cell infiltration and lead to improved sensitivity to anti-PD1 therapy.

Based on our preliminary results, TMB and PD-L1 can serve as potential early screening clinical biomarkers and molecular targets for immune treatment in ESCC. However, there is no apparent statistical association between TMB and PD-L1 expression levels. Furthermore, PD-L1 and TMB may independently influence the efficacy of immunotherapy, highlighting the inadequacy of single-marker detection in effectively predicting treatment outcomes.

Following surgery, she demonstrated a partial response to six cycles of conventional paclitaxel and carboplatin. She then received maintenance treatment with niraparib; however, disease progression subsequently occurred. The patient was treated with pembrolizumab and is currently receiving treatment with a partial response. Previous reports have demonstrated the efficacy of immune checkpoint inhibitors in 5 out of 6 cases of malignant transformation of mature teratomas, and this treatment appears to be a promising strategy. The online version contains supplementary material available at 10.1007/s13691-024-00740-z.

Overall, the study developed a unique IRS for LUAD that may serve as a predictor of the clinical outcome and immunotherapy advantages for individuals with LAUD.

PINK1 knockdown significantly inhibited the proliferation of BRCA cells. Our study developed a novel IRS for BRCA, which could predict the clinical outcome and immunotherapy benefits of BRCA patients.

Notable differences are present in the genomic landscape of CDX2-induced gastric cancer depending on the level of expression of SOX2 mRNA. Despite this, SOX2 mRNA expression levels were not prognostic.

In three cases, there was refinement or reassignment of the diagnosis, based on the CGP findings. Our results demonstrate that CGP can provide useful additional information and can be beneficial in the clinical management of patients with mesenchymal tumours.

In the second case, a 50-year-old woman with metastatic melanoma exhibited resistance to multiple systemic therapies, including nivolumab, ipilimumab, and targeted therapy with encorafenib and binimetinib. These cases highlight the variable therapeutic responses in melanoma with the BRAF L597 mutation, suggesting that immune checkpoint inhibitors may be a viable first-line treatment, particularly for patients with a high tumor mutational burden. Further studies are needed to establish optimal treatment strategies for this rare mutation.

The high tumor mutational burden and aggressive molecular profile align with the reported poor prognosis of dedifferentiated melanomas. Recognizing this rare variant is critical for accurate diagnosis, effective patient management, and prognosis assessment.

We have found that for women with pMBC, the disease is driven by several targetable genetic mutations across subtypes, however our results suggest a reduced prognostic value of TMB for this complex patient group. Taken together, our findings substantiate the value of early genomic profiling to actively identify women that may be eligible for a more individualized treatment scheme.

Genetic alterations with therapeutic relevance primarily include high TMB and high GIS. Previously unknown mutations suitable for targeted therapy were rarely identified, as almost all cases had previously undergone small targeted panel testing.

Preclinical testing of ObsERV demonstrates induction of sustained poly-functional CD4+ and CD8+ T-cell responses as well as long-term tumor protection. As such, EVEs may facilitate and improve PCVs, especially for low-TMB patients.

The advent of modern molecular profiling methods applied in the clinic, namely, next-generation sequencing and advanced positron emission tomography (PET) imaging, has allowed for the development of biomarker-driven therapeutics including anti-PD-L1 therapy for microsatellite instability-high or tumor mutation burden-high disease, poly(ADP-ribose) polymerase (PARP) inhibitors for patients with DNA damage repair mutations, and lutetium 177 vipivotide tetraxetan (177Lu-PSMA-617) for patients with prostate-specific membrane antigen (PSMA) PET-avid disease...The clinical management of NEPC typically follows the treatment paradigm for small cell lung cancer and increasingly relies on genomic and phenotypic characterization of disease, including loss of tumor suppressors and expression of cell surface markers such as DLL3. Therefore, both genomic subtyping and phenotypic subtyping are important to consider and can guide the clinical management of patients with advanced prostate cancer.

Our analysis reveals poor uptake of targeted therapies for rare NTRK fusions, significant differences in pembrolizumab-associated outcomes across tumor types for TMB-High and MSI-High/MMRd, as well as clinical benefits in tumor types and drugs of the same class not investigated in the pivotal clinical trials. These results demonstrate that treatment effects are not necessarily tissue-agnostic, and suggest possible expansion of therapeutic avenues for a given tissue-agnostic indication.

High-risk patients exhibit higher TMB and lower TIDE scores, and they are more likely to benefit from immunotherapy. The analysis of GEO verified that risk model has a high prediction accuracy.ConclusionThe risk model based on 17 FAM-related DEGs is of great value in predicting the prognosis of LUAD, and these prognostic signatures may be potential therapeutic targets for LUAD.

In addition, the patient developed an immune-related pneumonitis with a fatal outcome 3 months later. NGS with subsequent targeted treatment possibilities might present a helpful step toward precision medicine in GCT patients who have exhausted all other conventional treatment options, and genetic testing should therefore be offered to patients prior to progression.

After discussion at the interdisciplinary tumor board, a diagnosis of TMM was considered most likely, and the patient was initiated on pembrolizumab. Morphologic features more typical of MM than cutaneous sarcomas, such as tumor-infiltrating lymphocytes, junctional epidermal tumor nests, and satellitosis, may provide further clues to the accurate diagnosis of TMM, which has important prognostic and therapeutic implications for the patient.

Immune checkpoint inhibitor (ICI) therapy, particularly with PD-1 inhibitors like nivolumab, has become a critical treatment option for advanced NSCLC...These findings highlight the importance of TMB as a predictive biomarker, emphasizing the need for optimal treatment sequencing and personalized therapeutic strategies to overcome chemotherapy-induced immune resistance and maximize ICI treatment efficacy. These results suggest that ICI therapy may be more beneficial as a first-line treatment, particularly for patients with low TMB.

Despite the current therapeutic pipeline, research trying to develop new tailored drugs considering individual patient characteristics has evolved over the years. This article aims to outline the current therapeutic approach for each type of lung cancer and present the latest insights into emerging therapies, highlighting the role of personalized medicine in enhancing treatment outcomes and improving patients' quality of life.

Eight months after ten cycles of pembrolizumab treatment, multiple new nodules were observed in both lungs, indicating disease progression. This case highlights the utility of CGP testing in rare cancers, demonstrating the first evidence of TMB-high malignant phyllodes tumours of the breast responding to pembrolizumab and underscoring the value of expanding CGP testing to improve therapeutic strategies for rare cancers.

EGFR mutation subtypes and co-mutations differ by race. KMT2C may influence TMB and immunotherapy response, while GLI1 is linked to TKI resistance. TP53 alterations were more commen in smokers, and patients with high PDL-1 and TMB, highlighting additional factors that drive tumors with these alterations.

Neither MSI-H nor TMB-H, however, was sufficient for response. These results support biomarker testing for all patients with mPC and use of immunotherapy in select populations.

P1, N=12, Active, not recruiting, The Methodist Hospital Research Institute | Trial completion date: Dec 2024 --> Dec 2025

Cell lines without mutations in WNT/β-catenin/APC pathway components displayed numerically greater sensitivity to inhibitors of the pathway in vitro. Groups of colorectal cancers differing in WNT/β-catenin/APC pathway alterations present diverse genomic landscapes that could have therapeutic implications for the rational development of inhibitors of the pathway.

This approach is reflected in the growing list of FDA-approved tumor-agnostic therapies including pembrolizumab in the setting of microsatellite instability and high tumor mutational burden, larotrectinib and entrectinib for solid tumors with NTRK fusions, and combined dabrafenib-trametinib for BRAF V600E-mutated neoplasms. Several other biomarkers are currently under investigation including FGFR, RET, and ROS1 fusions; ERBB2 amplification; and mutations in the AKT1/2/3, NF1, RAS pathway, and MAPK pathway. As molecular assays are increasingly incorporated into routine tumor workup, the emergence of additional pan-cancer biomarkers is likely to be a matter more of "when" than "if." In this review, we first explore some of the conceptual and technical considerations at the intersection of surgical and molecular pathology, followed by a brief overview of both established and emerging molecular pan-cancer biomarkers and their diagnostic and clinical applications.

Following a tumor board recommendation, systemic immunotherapy with cemiplimab was initiated...Incidence and nature of adverse events in XP patients were comparable to those observed in the general population. In line with the previously reported ICI-treated XP children, the present case confirms that anti-PD-1 inhibitors are highly effective in children with XP and advanced cSCC.

This perspective discusses a novel approach of analysing spatial TILs at a single-cell level using tumor whole slide images (WSIs) that accounts for the distinct TME of LS-CRC. By emphasizing the necessity of personalized medicine in hereditary cancer syndromes, the future research and clinical practices that enhance patient outcomes through precision oncology is inspired.

This study is the first to reveal the SCPC genomic landscape in Japanese patients. Although genomic mutations, including DDR mutations, were not predictive of platinum-based chemotherapy efficacy, active genomic testing may improve access to targeted therapies for this challenging malignancy, especially where treatment options are limited.

Our findings relate specific molecular alterations of GC tumors from Europe and LATAM to actionable biomarkers for precision cancer therapies. The proposed GC stratification can be implemented in routine care and guide drug development strategies.