PD-1 inhibition is effective in patients with mismatch repair deficient (dMMR) solid tumors in a tumor-agnostic fashion. However, dMMR testing by immunohistochemistry (IHC) is not routinely performed across tumor types. By contrast, next-generation sequencing (NGS) for somatic genomic alterations is frequently performed across tumor types. We hypothesized that NGS would identify patients with alterations in mismatch repair (MMR) genes and that these patients would have higher rates of MMR protein loss by IHC. This would support the utility of IHC reflex testing after NGS and potential matching to approved therapeutic options.

BRAF and MEK inhibitors are standard treatments in histiocytic disorders, such as Erdheim-Chester disease (ECD). Some patients lack MAPK-pathway alterations, making these treatments less effective.

Alterations in DNA damage response (DDR) genes, including , have been correlated with response to neoadjuvant cisplatin-based chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC). The SWOG 1314 (S1314) trial enrolled patients with MIBC who received one of two NAC regimens followed by radical cystectomy. We examined the prevalence of DDR alterations in NAC responders versus nonresponders and correlated DDR alteration status with response.

Patients with stage II and III cutaneous primary melanoma vary considerably in their risk of melanoma-related death. We explore the ability of methylation profiling to distinguish primary melanoma methylation classes and their associations with clinicopathologic characteristics and survival.

KRASG12D mutation (mut) occurs in about 10%-12% of metastatic colorectal cancer (mCRC). Recently, novel KRASG12D inhibitors have been developed and are currently under investigation in phase I/II clinical trials in solid tumors including mCRC. We aimed at performing a comprehensive characterization of clinical, molecular, immunologic, and prognostic features of KRASG12D-mutated mCRC to inform the design and the interpretation of future trials.

The activity of osimertinib is not fully characterized in non-small-cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor () mutations. Therefore, we conducted a systematic review and meta-analysis to assess the safety and efficacy of osimertinib in patients with NSCLC harboring uncommon somatic mutations.

Histone deacetylase (HDAC) inhibition downregulates hypoxia-inducible factor-1α and modulates multiple metabolomic pathways relevant in cancer. Here we report a potential novel biomarker to predict exceptional responders (>3 years) in patients receiving HDAC and vascular endothelial growth factor (VEGF) inhibition.

In lung squamous cell carcinoma (LUSC), Black patients show significantly higher incidence and lower overall survival than White patients. Although socioeconomic factors likely contribute to this survival disparity, genomic factors have yet to be elucidated in LUSC.

Clinical utility of comprehensive genomic profiling (CGP) for precision medicine has become evident. Although there are several reports on the genomic landscape of GI stromal tumors (GISTs), large-scale data specific to GIST are limited, especially in Asia. Additionally, the applicability of molecular-targeted agents identified using CGP has not been extensively examined. We investigated the status of genomic alterations in Japanese patients with advanced GISTs using the National Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database to identify novel treatment strategies and drug development.

Precision oncology relies on accurate and interpretable reporting of testing and mutation rates. Focusing on the mutations in advanced colorectal carcinoma, non-small-cell lung carcinoma, and cutaneous melanoma, we developed a platform displaying testing and mutation rates reported in the literature, which we annotated using an artificial intelligence (AI) and natural language processing (NLP) pipeline.

Rapidly expanding medical literature challenges oncologists seeking targeted cancer therapies. General-purpose large language models (LLMs) lack domain-specific knowledge, limiting their clinical utility. This study introduces the LLM system Medical Evidence Retrieval and Data Integration for Tailored Healthcare (MEREDITH), designed to support treatment recommendations in precision oncology. Built on LLM, MEREDITH uses and .

Antibody-drug conjugates (ADCs) are at the forefront of cancer therapy, combining targeted precision with potent cytotoxicity. Conceived by Paul Ehrlich in the early 1900s, the concept of a magic bullet selectively eliminating cancer cells has evolved alongside bioengineering and cancer biology advancements. ADCs consist of a monoclonal antibody, linker, and cytotoxic payload, designed to target specific antigens on tumor cells while minimizing collateral damage. Mechanistically, ADCs are internalized via endocytosis, releasing the cytotoxic payload within the lysosome, potentially affecting neighboring tumor cells. ADC development has progressed through multiple generations, each addressing limitations of its predecessors. From gemtuzumab ozogamicin to trastuzumab emtansine (T-DM1), and now to third-generation agents such as trastuzumab deruxtecan (DS-8201) and disitamab vedotin (RC48), improvements have been made in target selectivity, potency, linker stability, and reduced off-target effects. Significant success has been seen in ADCs targeting human epidermal growth factor receptor 2 and trophoblast cell-surface antigen 2 antigens, especially in patients with breast cancer, including those resistant to previous therapies. The future of ADCs includes exploring new surface antigens, bispecific antibodies, immune-activating antibodies, radiopharmaceutical-loaded ADCs, and masked ADCs for tissue-specific activation. Ongoing research aims to optimize treatment efficacy while minimizing toxicity, expanding the potential of combination therapy. ADCs represent a promising frontier in precision cancer treatment, with continued research enhancing their potential in breast cancer and beyond. This review provides a comprehensive exploration of ADCs' evolution in breast cancer therapy, offering a molecular perspective to inform clinical practice and update colleagues on this dynamic field.

Individuals with Lynch syndrome (LS) are at a high lifetime risk of colorectal cancer (CRC) and other cancers. Aspirin (ASA), a nonsteroidal anti-inflammatory drug (NSAID), has proven chemopreventive benefits in LS, with the CAPP2 randomized double-blind placebo-controlled trial demonstrating a 60% relative risk reduction for CRC among participants who adhered to ASA for 2 years or more. This study sought to characterize uptake of ASA/NSAIDs among individuals with LS and to understand factors associated with use.

Dynamics of carbohydrate antigen 19-9 (CA19-9) often inform treatment decisions during and after neoadjuvant chemotherapy (NAT) of patients with pancreatic ductal adenocarcinoma (PDAC). However, considerable dispute persists regarding the clinical relevance of specific CA19-9 thresholds and dynamics. Therefore, we aimed to define optimal thresholds for CA19-9 values and create a biochemically driven composite score to predict survival in CA19-9-producing patients with PDAC after NAT.

The new CAP guideline published in August 2022 recommends using immunohistochemistry (IHC) to test for mismatch repair defects in gastroesophageal (GE), small bowel (SB), or endometrial carcinoma (EC) cancers over next-generation sequencing assessment of microsatellite instability (NGS-MSI) for immune checkpoint inhibitor (ICI) therapy eligibility and states there is a preference to use IHC over NGS-MSI in colorectal carcinoma (CRC).

CD8 tumor-infiltrating lymphocytes (TILs) are increasingly used in oncology as a prognostic and predictive tool to guide patient management. This review summarizes current literature on CD8 TILs in head and neck squamous cell carcinoma (SCC). Published meta-analyses and clinical trials evaluating CD8 TILs were analyzed. Consistent positive associations between elevated CD8 TILs and overall survival have been observed across head and neck sites. CD8 TILs have been found to predict response to treatment, most commonly immunotherapy, but also chemoradiation. Numerous trials have shown that increased CD8 TIL frequencies in pretreatment biopsies could identify patients likely to respond to neoadjuvant therapies. CD8 TIL infiltration has also been elevated in responders both during and after treatment. However, wider adoption of CD8 TIL quantification as a biomarker has been limited by the need for clinical validation and universal measurement guidelines for head and neck SCC, as there are for other malignancies. Measurement variability includes which tumor compartment is sampled, how TILs are quantified, and which cutoffs are clinically relevant. For several head and neck SCC, measurement of CD8 TILs in the central or intratumoral compartment, followed by the stromal compartment, has been most consistently associated with survival. Future studies are needed to evaluate subpopulations of CD8 TILs and biomarker-based treatment selection.