Sarcomatoid carcinoma of the pancreas (SCP) is a rare and aggressive subtype of undifferentiated pancreatic ductal adenocarcinoma, with a generally poor prognosis and only sporadic cases reported worldwide. Histologically, the most notable feature of SCP is the presence of abundant of mesenchymatoid spindle tumor cells in the tumor, which lack glandular differentiation. Immunohistochemically, SCP is characterized by the expression of both mesenchymal and epithelial markers. With only a few reported cases, there is limited knowledge about its molecular and clinicopathological characteristics. Therefore, the present study performed a literature search to identify all relevant published studies. The present review provides an overview of the histogenesis, diagnosis, genetic features, prognosis and treatment of SCP, specifically focusing on the molecular alterations. Furthermore, a single-center experience is reported, which adds to the limited evidence available in the literature.

Precision oncology promises individually tailored drugs and clinical care for patients with cancer: That is, \"the right drug, for the right patient, at the right dose, and at the right time.\" Although stratification of the risk for treatment resistance and toxicity is key to precision oncology, there are multiple ways in which such stratification can be achieved, for example, genetic, functional pathway based, among others. Moving toward precision oncology is sorely needed in the case of acute lymphoblastic leukemia (ALL) wherein adult patients display survival rates ranging from 30% to 70%. The present study reports on the pathway activity signature of adult B-ALL, with an eye to precision oncology. Transcriptome profiles from three different expression datasets, comprising 346 patients who were adolescents or adults with B-ALL, were harnessed to determine the activity of signaling pathways commonly disrupted in B-ALL. Pathway activity analyses revealed that Ph-like ALL closely resembles Ph-positive ALL. Although this was the case at the average pathway activity level, the pathway activity patterns in B-ALL differ from genetic subtypes. Importantly, clustering analysis revealed that five distinct clusters exist in B-ALL patients based on pathway activity, with each cluster displaying a unique pattern of pathway activation. Identifying pathway-based subtypes thus appears to be crucial, considering the inherent heterogeneity among patients with the same genetic subtype. In conclusion, a pathway-based stratification of the B-ALL could potentially allow for simultaneously targeting highly active pathways within each ALL subtype, and thus might open up new avenues of innovation for personalized/precision medicine in this cancer that continues to have poor prognosis in adult patients compared with the children.

BACKGROUND: High-throughput sequencing techniques have revolutionized oncology. Paired germline-tumor DNA analysis has emerged as a comprehensive strategy to uncover actionable alterations in advanced cancer patients (ACP) enrolled in precision oncology trials. However, challenges persist in variant interpretation and managing incidental germline findings.
METHODS: We conducted a study involving 288 ACP from MOSCATO (NCT01566019) and MATCHR (NCT02517892) trials to assess germline variants impacting cancer-related genes. Germline DNA sequencing was performed using a panel of 250 cancer-related genes, and the results were discussed during tumor molecular board sessions.
RESULTS: Germline pathogenic variants (PV) were classified according to the ESCAT classification. Lung cancer (36.8 %), followed by prostate (18.4 %) and breast cancer (17.7 %), comprised the most prevalent tumor types. PVs were found in 12.5 % of patients. Most PVs were classified as ESCAT X (63.9 %), highlighting limited therapeutic actionability. Notably,2 % of patients had actionable variants (ESCAT I-A/II-A). Incidental findings included 7.3 % of patients with PVs in cancer-predisposition genes, with 2.4 % having very high-risk potential, necessitating mandatory oncogenetic counseling. Nearly one in five patients (21.9 %) had at least one VUS.
CONCLUSIONS: Our study underscores the significance of germline sequencing in identifying actionable alterations and the need for improved variant interpretation as well as pretest counseling plans in precision oncology trials.

Cancer continues to present a substantial global health challenge, with its incidence and mortality rates persistently reflecting its significant impact. The emergence of precision oncology has provided a breakthrough in targeting oncogenic drivers previously deemed \"undruggable\" by conventional therapeutics and by limiting off-target cytotoxicity. Two groundbreaking technologies that have revolutionized the field of precision oncology are primarily CRISPR-Cas9 gene editing and more recently PROTAC (PROteolysis TArgeting Chimeras) targeted protein degradation technology. CRISPR-Cas9, in particular, has gained widespread recognition and acclaim due to its remarkable ability to modify DNA sequences precisely. Rather than editing the genetic code, PROTACs harness the ubiquitin proteasome degradation machinery to degrade proteins of interest selectively. Even though CRISPR-Cas9 and PROTAC technologies operate on different principles, they share a common goal of advancing precision oncology whereby both approaches have demonstrated remarkable potential in preclinical and promising data in clinical trials. CRISPR-Cas9 has demonstrated its clinical potential in this field due to its ability to modify genes directly and indirectly in a precise, efficient, reversible, adaptable, and tissue-specific manner, and its potential as a diagnostic tool. On the other hand, the ability to administer in low doses orally, broad targeting, tissue specificity, and controllability have reinforced the clinical potential of PROTAC. Thus, in the field of precision oncology, gene editing using CRISPR technology has revolutionized targeted interventions, while the emergence of PROTACs has further expanded the therapeutic landscape by enabling selective protein degradation. Rather than viewing them as mutually exclusive or competing methods in the field of precision oncology, their use is context-dependent (i.e., based on the molecular mechanisms of the disease) and they potentially could be used synergistically complementing the strengths of CRISPR and vice versa. Herein, we review the current status of CRISPR and PROTAC designs and their implications in the field of precision oncology in terms of clinical potential, clinical trial data, limitations, and compare their implications in precision clinical oncology.

Skin cancer comprises one-third of all diagnosed cancer cases and remains a major health concern. Genetic and environmental parameters serve as the two main risk factors associated with the development of skin cancer, with ultraviolet radiation being the most common environmental risk factor. Studies have also found fair complexion, arsenic toxicity, indoor tanning, and family history among the prevailing causes of skin cancer. Prevention and early diagnosis play a crucial role in reducing the frequency and ensuring effective management of skin cancer. Recent studies have focused on exploring minimally invasive or non-invasive diagnostic technologies along with artificial intelligence to facilitate rapid and accurate diagnosis. The treatment of skin cancer ranges from traditional surgical excision to various advanced methods such as phototherapy, radiotherapy, immunotherapy, targeted therapy, and combination therapy. Recent studies have focused on immunotherapy, with the introduction of new checkpoint inhibitors and personalized immunotherapy enhancing treatment efficacy. Advancements in multi-omics, nanotechnology, and artificial intelligence have further deepened the understanding of the mechanisms underlying tumoral growth and their interaction with therapeutic effects, which has paved the way for precision oncology. This review aims to highlight the recent advancements in the understanding and management of skin cancer, and provide an overview of existing and emerging diagnostic, prognostic, and therapeutic modalities, while highlighting areas that require further research to bridge the existing knowledge gaps.

(1) Background: Pancreatic ductal adenocarcinoma (PDAC) has low survival rates despite treatment advancements. Aim: This study aims to show how molecular profiling could possibly guide personalized treatment strategies, which may help improve survival outcomes in patients with PDAC. (2) Materials and Methods: A retrospective analysis of 142 PDAC patients from a single academic center was conducted. Patients underwent chemotherapy and next-generation sequencing for molecular profiling. Key oncogenic pathways were identified using the Reactome pathway database. Survival analysis was performed using Kaplan-Meier curves and Cox Proportional Hazards Regression. (3) Results: Patients mainly received FOLFIRINOX (n = 62) or gemcitabine nab-paclitaxel (n = 62) as initial chemotherapy. The median OS was 13.6 months. Longer median OS was noted in patients with NOTCH (15 vs. 12.3 months, p = 0.007) and KIT pathway mutations (21.3 vs. 12.12 months, p = 0.04). Combinatorial pathway analysis indicated potential synergistic effects on survival. In the PFS, PI3K pathway (6.6 vs. 5.7 months, p = 0.03) and KIT pathway (10.3 vs. 6.2 months, p = 0.03) mutations correlated with improved PFS within the gemcitabine nab-paclitaxel subgroup. (4) Conclusions: Molecular profiling could play a role in PDAC for predicting outcomes and responses to therapies like FOLFIRINOX and gemcitabine nab-paclitaxel. Integrating genomic data into clinical decision-making can benefit PDAC treatment, though further validation is needed to fully utilize precision oncology in PDAC management.

The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 system, a groundbreaking innovation in genetic engineering, has revolutionized our approach to surmounting complex diseases, culminating in CASGEVY™ approved for sickle cell anemia. Derived from a microbial immune defense mechanism, CRISPR/Cas9, characterized as precision, maneuverability and universality in gene editing, has been harnessed as a versatile tool for precisely manipulating DNA in mammals. In the process of applying it to practice, the consecutive exploitation of novel orthologs and variants never ceases. It\'s conducive to understanding the essentialities of diseases, particularly cancer, which is crucial for diagnosis, prevention, and treatment. CRISPR/Cas9 is used not only to investigate tumorous genes functioning but also to model disparate cancers, providing valuable insights into tumor biology, resistance, and immune evasion. Upon cancer therapy, CRISPR/Cas9 is instrumental in developing individual and precise cancer therapies that can selectively activate or deactivate genes within tumor cells, aiming to cripple tumor growth and invasion and sensitize cancer cells to treatments. Furthermore, it facilitates the development of innovative treatments, enhancing the targeting efficiency of reprogrammed immune cells, exemplified by advancements in CAR-T regimen. Beyond therapy, it is a potent tool for screening susceptible genes, offering the possibility of intervening before the tumor initiative or progresses. However, despite its vast potential, the application of CRISPR/Cas9 in cancer research and therapy is accompanied by significant efficacy, efficiency, technical, and safety considerations. Escalating technology innovations are warranted to address these issues. The CRISPR/Cas9 system is revolutionizing cancer research and treatment, opening up new avenues for advancements in our understanding and management of cancers. The integration of this evolving technology into clinical practice promises a new era of precision oncology, with targeted, personalized, and potentially curative therapies for cancer patients.

The liver is a frequent site of metastasis in advanced gastric cancer (GC). Despite significant advancements in diagnostic and therapeutic techniques, the overall survival rate for patients afflicted with gastric cancer liver metastasis (GCLM) remains dismally low. Precision oncology has made significant progress in identifying therapeutic targets and enhancing our understanding of metastasis mechanisms through genome sequencing and molecular characterization. Therefore, it is crucial to have a comprehensive understanding of the various molecular processes involved in GCLM and the fundamental principles of systemic therapy to develop new treatment approaches. This paper aims to review recent findings on the diagnosis, potential biomarkers, and therapies targeting the multiple molecular processes of GCLM, with the goal of improving treatment strategies for patients with GCLM.

UNASSIGNED: Next-generation sequencing (NGS) identifies genetic variants to inform personalized treatment plans. Insufficient evidence of cost-effectiveness impedes the integration of NGS into routine cancer care. The complexity of personalized treatment challenges conventional economic evaluation. Clearly delineating challenges informs future cost-effectiveness analyses to better value and contextualize health, preference-, and equity-based outcomes.
UNASSIGNED: We conducted a scoping review to characterize the applied methods and outcomes of economic evaluations of NGS in oncology and identify existing challenges. We included 27 articles published since 2016 from a search of PubMed, Embase, and Web of Science. Identified challenges included defining the evaluative scope, managing evidentiary limitations including lack of causal evidence, incorporating preference-based utility, and assessing distributional and equity-based impacts. These challenges reflect the difficulty of generating high-quality clinical effectiveness and real-world evidence (RWE) for NGS-guided interventions.
UNASSIGNED: Adapting methodological approaches and developing life-cycle health technology assessment (HTA) guidance using RWE is crucial for implementing NGS in oncology. Healthcare systems, decision-makers, and HTA organizations are facing a pivotal opportunity to adapt to an evolving clinical paradigm and create innovative regulatory and reimbursement processes that will enable more sustainable, equitable, and patient-oriented healthcare.

UNASSIGNED: Despite several therapeutic advancements, the proportion of patients with advanced biliary tract cancers (BTC) surviving 5 years from diagnosis remains dismal. The increasing recognition of targetable genetic alterations in BTCs has ushered in a new era in the treatment of these patients. Newer therapeutic agents targeting mutations such as isocitrate dehydrogenase (IDH), fibroblastic growth factor receptor (FGFR), human epidermal growth factor receptor (HER), and so on have established a new standard of care for treatment upon progression on frontline therapy in patients with disease harboring these mutations.
UNASSIGNED: The current review aims to concisely summarize progress with various targeted therapy options for BTC. We also briefly discuss future directions in clinical and translational research for the adoption of a personalized approach for the treatment of unresectable or advanced BTC.
UNASSIGNED: Several new agents continue to emerge as feasible treatment options for patients with advanced BTC harboring targetable mutations. There is a growing need to identify mechanisms to conquer primary and acquired resistance to these agents. The identification of potential biomarkers that predict response to targeted therapy may be helpful in adopting a more tailored approach. All patients receiving treatment for advanced BTC should undergo tissue genomic profiling at diagnosis.