HER-2 (Human epidermal growth factor receptor 2)

The FGFR and IDH-1 pathways are the primary targets for therapy, with FGFR-2 and IDH-1 inhibitors, such as Pemigatinib and Ivosidenib respectively, already available on the market. This prospective study validates the prevalence of mutations documented in the literature and underscores the significance of NGS in presenting supplementary therapeutic avenues. Moreover, we demonstrated the role of other potential targets co-expressed with FGFR2 or IDH1 which could represent a crucial opportunity for novel combinations or sequences therapies.

Blood-based LB performed by NGS is a non-invasive viable alternative tool for molecular genotyping and identifiy tumor-derived somatic alterations to increase the number of pts elegible to target therapy and guide personalized medicine.

Our study provides an example of implementation of molecular profiling in an academic pre-screening program. Further analysis will investigate treatment matching rates, drug access schemes, and their impact on treatment efficacy and survival.

According to literature, and TailorX trial data, our study confirms the importance of ODX as a tool able to guide therapeutic choices and ensure patients the most appropriate adjuvant treatment.

Materials and The phase II CAPRI 2-GOIM trial investigates the efficacy and safety of biomarkerdriven, cetuximab-based, sequence of three treatment lines in mCRC... Baseline plasma-based comprehensive genomic profiling is feasible with high concordance with tissue-based analysis. Liquid biopsy allows identification of misdiagnosed RAS/BRAF alterations and the ultra-selection of pts, which could benefit from anti-EGFR therapies. Finally, potentially actionable gene alterations were found in half of the pts.

Longitudinal multimodal DL can be useful in predicting pCR. The stacking model can be used as a new tool for the early noninvasive prediction of the response to NAC, as evidenced by its excellent performance, and therefore aid the development of personalized treatment strategies for patients with breast cancer.

Our study revealed novel functions of DLL4 in cell stemness and immune infiltration, including NET formation and T cell exclusion, which collectively contributed to THP neoadjuvant therapy resistance in HER2+ BC. Furthermore, we provided a CAR-T-based therapy to sensitize the THP neoadjuvant therapy.

The MNAzyme biosensor exhibited a low detection limit of 0.02 ng mL-1 and excellent selectivity. Furthermore, the proposed biosensor can also change the recognition element by changing the aptamer sequence to detect various biomarkers, holding great potential for cancer diagnosis and other related biomedical applications.

Fourteen different articles showed that the use of cytokines and cancer vaccines revealed new possibilities to treat breast cancer with antibodies against PD-1/PD-L1 (pembrolizumab), PI3K/Akt/mTOR (alpelisib and everolimus), CAR T-cell (chimeric antigen receptor), PARP (poly ADP-ribose polymerase), and CTLA4 (cytotoxic T-lymphocyte-associated protein 4), and with representative relevance of changing in tumor microenvironment. Estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) targets show also a high effectivity. In recent years, the release of new strategies has become promising, for changing the microenvironment and de-escalation of therapy based on tumor biology, novel biomarkers, and tumor spread.

We achieved a remarkable response in the metastatic lesions with minor toxicity issues. This case highlights the importance of utilizing up-to-date therapeutic agents and reactive decision-making during personalized cancer treatment.

Our findings show that CEACAM5, EGFR and EpCAM are promising targets for molecular imaging of primary gastric cancer, as well as visualization of both lymph node and distant metastases. Further clinical evaluation of PET and FGS tracers targeting these antigens is warranted.

This INFLUENCE 3.0 models showed moderate performance in LRR and CBC prediction. The models have been made available as online tool to enable clinical decision support regarding personalised follow-up.

If patients with synchronous GCPM have stable disease following neoadjuvant therapy, surgical intervention can be considered. Patients with positive cytology or low-volume peritoneal disease (peritoneal carcinomatosis index &lsqb;PCI] < 7) may "convert" to negative cytology or resolution of peritoneal metastases following intraperitoneal therapy and may be candidates for subsequent gastrectomy.

Finally, sTIL levels were significantly higher in lung and axillary lymph node metastases compared to all metastases. While these analyses were conducted on multiple metastases obtained at the end of life after several lines of treatment, the data provides novel and valuable insights into the state of immune infiltration in patients with metastatic HR+/HER2- BC.

Physicians should make additional efforts to evaluate age-specific treatment efficacy and treatment-induced toxicities. Further efforts to enhance the representation of older patients in breast cancer trials are warranted.

Considering all these data, we can conclude that the expression of immunoregulatory genes depends on tumor phenotype and has potential clinical implications in BC patients.

HER2 and other tumor-associated antigens have served as valuable benchmarks for developing novel therapies, such as antibody engagers and CAR T-cells. However, further research is essential to identify and validate new target antigens that can enhance therapeutic efficacy and broaden the clinical applicability of these approaches.

There were significant differences between the CR and ML models in predicting LVI status. Our study demonstrated that the machine learning models exhibited superior performance in predicting LVI status based on pretreatment MRI compared to the CR model, which does not necessarily rely on a priori knowledge of visual morphology.

Collectively, these findings suggest that CCTR offers superior predictive information compared to KI and MI alone with respect to long-term outcomes from adjuvant chemotherapy in patients with TNBC that may guide treatment decision making.

In comparison with recommended diagnostic algorithms, NGS provides a more reliable classification of EC into particular molecular subgroups. Furthermore, NGS reveals the complex molecular genetic background in individual ECs, which is especially significant within ECs with no specific molecular profile. These data can serve as a springboard for the research of therapeutic programs committed to targeted therapy in this type of tumor.

Neoadjuvant cadonilimab plus FLOT chemotherapy treatment exhibits promising efficacy with manageable toxicities in locally advanced G/GEJ adenocarcinoma, providing preliminary evidence for further investigation.

This review focuses on the topic of tumor-on-a-chip, microfluidic chip manufacturing, and drug screening for triple-negative breast cancer. Particular emphasis is placed on cancer biomarker diagnostics, 3D preclinical model development, and treatment strategies for triple-negative breast cancer.

Endocrine therapy plus CDK 4/6i represents an effective treatment, regardless of HER2 status (low/zero). Second-line agents did not differ significantly in terms of TTD. Endocrine resistant cancers exhibit poor response to CDK 4/6i.

Broadly, our findings suggest that cancer often arrogates normal tissue transcriptomic characteristics as a component of both malignant progression and drug response. This quantitative framework provides a strategy for connecting the diversity of cancer phenotypes and could potentially help manage individual patients.

Moreover, we found that co-administration of pharmacological inhibitors of HER2 and TRPM7 elicited a synergistic antiproliferative effect on HER2-overexpressing SKBR3 cells but not on HER2-deficient MDA-MB-231 breast cancer cells. Hence, our study proposes a new combinatorial strategy for treating HER2-positive breast cancer cells.

PSS validates a previously developed ddPCR classifier: 100 copies/mL (2.5% VAF); and confirms progression, with negative predictive value (95% CI) of 83% (76%-88%) and positive predictive value (95% CI) of 91% (81%-96%) (weighted κ, 0.856; 95% CI, 0.797-0.915). PSS thus confirms robust clinical thresholds (10 to 100 copies/mL, 0.25% to 2.5% VAF) for metastatic breast cancer surveillance, using absolute molecular counting.

Less than one-third of BC patients completed treatment, and the majority faced financial catastrophe, especially those with HER2+/HR ​+ ​disease and patients who underwent multiple treatment modalities or immunotherapy. Targeted efforts are essential to ensure equitable access to quality cancer care while minimizing risk of financial catastrophe.

Measures of the spatial distributions of immune cells within the tumor microenvironment, in particular colocalization or close spatial proximity of PD-1+ T cells with PD-L1+ cells (immune and tumor cells), are significantly associated with response in the overall cohort as well as the in the triple negative (TN) and HR+HER2- subtypes. Our findings indicate that biomarkers associated with immune cell signaling, immune cell densities, and spatial metrics are predictive of neoadjuvant ICB efficacy in breast cancer.

Furthermore, 48 women with luminal/HER2-low (IHC 2+/FISH-negative) high-risk EBC are enrolled to receive neoadjuvant pyrotinib plus chemotherapy (epirubicin-cyclophosphamide followed by docetaxel). In conclusion, neoadjuvant pyrotinib plus chemotherapy has encouraging efficacy and manageable toxicity in women with luminal/HER2-low (IHC 2+/FISH-negative) high-risk EBC. This regimen warrants to be further validated.

Dose-dense chemotherapy regimens and the addition of carboplatin have been associated with an improvement in these response rates. Furthermore, immunotherapy, particularly pembrolizumab, has shown significant benefits in terms of recurrence-free survival...In conclusion, despite recent progress, TNBC remains a major clinical challenge. A better understanding of its biology and a personalized therapeutic approach are essential to improve clinical outcomes for patients with this aggressive form of breast cancer.

The economic viability of dual HER2-targeted therapy was most pronounced in patients with node-positive high-risk early breast cancer. This study highlights the potential of dual HER2-targeted therapy as a cost-effective addition for these cases.

These findings highlighted specific lipid features and interactions that may serve as potential biomarkers for breast cancer classification and target pathways for therapeutic intervention. Furthermore, advanced lipidomic analyses can be integrated to decipher complex biological data, offering a foundation for further research into the role of lipid metabolism in cancer progression.

This result was superior to the second-line treatment with nab-paclitaxel, which resulted in a PFS of 8 months and best overall response of stable disease with slight shrinkage. The present case indicates that a combination of utidelone with apatinib/anlotinib exhibited antitumor activity in a patient with HR+/HER2- mBC with BMs. Therefore, this combination offers a promising therapeutic option for the clinical treatment of patients with breast cancer and BMs.

Molecular docking studies supported the experimental findings, confirming the binding of the novel motifs to the target enzymes' active sites. This comprehensive evaluation highlights the potential of these triazolopyrimidine compounds, particularly 13c, as promising anticancer agents, warranting further investigation.

His resistance to trastuzumab was overcome after the addition of a PD-1 inhibitor, after which he received a durable response for more than 8 months. In HER2-positive, PD-L1-negative metastatic GC, the addition of PD-1 inhibitors after first-line chemotherapy and trastuzumab treatment resistance may be an option.

Drug sensitivity to the HER2 kinase inhibitor lapatinib was characterized under conditions of monoculture and exposure to breast fibroblast-conditioned medium...Combination therapies targeting HER2 kinase and these fibroblast-induced signaling adaptations eliminates fibroblast-protected HER2+ breast cancer cells. The online version contains supplementary material available at 10.1007/s12195-024-00823-0.

The incidence of adverse events (AEs) was generally consistent across all levels. There were slight differences in the mean Cmax, Cmin, AUCtau and Cav between the three-week dosing group and the single-week dosing group, and the mean steady-state concentrations of Cav were comparable; however, there were no differences in efficacy, safety or immunogenicity between the two groups.

The study firstly presents a non-invasive method for identifying and detecting HER2 expression in BCa CTU images. It might not only reduce the cost and subjectivity of traditional HER2 testing but also provide a new technical method for the precise treatment of BCa.

They can also differentiate individual cancer stages except those between Stage III and Stage IV. Due to the simplicity, high sensitivity, and high efficiency, the DISVT with the AI-assisted dual imaging analysis can be widely used for both basic research and clinical applications to quantitatively characterize molecularly targeted EV subtypes in biofluids.

Despite the rarity of NTRK fusions in pancreatic cancer, larotrectinib and entrectinib have exhibited effectiveness in NTRK fusion-positive pancreatic cancers. Additionally, repotrectinib, a next-generation NTRK inhibitor, has shown promising activity in NTRK positive pancreatic cancer patients who have developed acquired resistance to previous NTRK inhibitors. Immune checkpoint inhibitors, such as pembrolizumab and dostarlimab, have proven to be effective in dMMR/MSI-H pancreatic cancers...It is crucial to continue implementing comprehensive screening strategies that encompass the ability to detect all these tumor-agnostic biomarkers. This will be essential in identifying pancreatic cancer patients who may benefit from these therapies.

Patients with the HR+/HER2- subtype showed an increased risk of LRR after NACT, while those with other subtypes showed comparable LRR-free survival.

We also discuss the challenges and opportunities originating from recent clinical trials evaluating targeted treatments and our own institutional experience at UCLH that have aimed to address some of these biological complexities and have translated into improved patient outcomes via effective molecularly driven patient selection strategies. We also provide perspectives on emerging novel, next generation targeted inhibitors overcoming treatment resistance to previous targeted agents with demonstrated clinical value in a challenging patient population.