Interleukin-2 (IL-2) and its receptor (IL-2R) are essential in orchestrating immune responses. Their function and expression in the tumor microenvironment make them attractive targets for immunotherapy, leading to the development of IL-2/IL-2R-targeted therapeutic strategies. However, the dynamic interplay between IL-2/IL-2R and various immune cells and their dual roles in promoting immune activation and tolerance presents a complex landscape for clinical exploitation. This review discusses the pivotal roles of IL-2 and IL-2R in tumorigenesis, shedding light on their potential as diagnostic and prognostic markers and their therapeutic manipulation in cancer. It underlines the necessity to balance the anti-tumor activity with regulatory T-cell expansion and evaluates strategies such as dose optimization and selective targeting for enhanced therapeutic effectiveness. The article explores recent advancements in the field, including developing genetically engineered IL-2 variants, combining IL-2/IL-2R-targeted therapies with other cancer treatments, and the potential benefits of a multidimensional approach integrating molecular profiling, immunological analyses, and clinical data. The review concludes that a deeper understanding of IL-2/IL-2R interactions within the tumor microenvironment is crucial for realizing the full potential of IL-2-based therapies, heralding the promise of improved outcomes for cancer patients.

UNASSIGNED: Patients with inoperable extrabronchial or endobronchial tumors who are not candidates for curative radiotherapy have dire prognoses with no effective long-term treatment options. To reveal that our computer-optimized interstitial photodynamic therapy (I-PDT) is safe and potentially effective in the treatment of patients with inoperable extra or endobronchial malignancies inducing central airway obstructions.
UNASSIGNED: High-spatial resolution computer simulations were used to personalize the light dose rate and dose for each tumor. Endobronchial ultrasound with a transbronchial needle was used to place the optical fibers within the tumor according to an individualized plan. The primary and secondary end points were safety and overall survival, respectively. An exploratory end point evaluated changes in immune markers.
UNASSIGNED: Eight patients received I-PDT with planning, and five of these received additional external beam PDT. Two additional patients received external beam PDT. The treatment was declared safe. Three of 10 patients are alive at 26.3, 12, and 8.3 months, respectively, after I-PDT. The treatments were able to deliver a prescribed light dose rate and dose to 87% to 100% and 18% to 92% of the tumor volumes, respectively. A marked increase in the proportion of monocytic myeloid-derived suppressor cells expressing programmed death-ligand 1 was measured in four of seven patients.
UNASSIGNED: Image-guided light dosimetry for I-PDT with linear endobronchial ultrasound transbronchial needle is safe and potentially beneficial in increasing overall survival of patients. I-PDT has a positive effect on the immune response including an increase in the proportion of programmed death-ligand 1-expressing monocytic myeloid-derived suppressor cells.

The presentation of neoantigens on the cell membrane is the foundation for most cancer immunotherapies. Due to their extremely low abundance, analyzing neoantigens in clinical samples is technically difficult, hindering the development of neoantigen-based therapeutics for more general use in the treatment of diverse cancers worldwide. Here, we describe an integrated system, \"Valid-NEO\", which reveals patient-specific cancer neoantigen therapeutic targets from minute amounts of clinical samples through direct observation, without computer-based prediction, in a sensitive, rapid, and reproducible manner. The overall four-hour procedure involves mass spectrometry analysis of neoantigens purified from tumor samples through recovery of HLA molecules with HLA antibodies. Valid-NEO could be applicable to the identification and quantification of presented neoantigens in cancer patients, particularly when only limited amounts of sample are available.

Angiogenesis inhibitors (AGI) are not presently used for the treatment of gastric cancers. This report demonstrates that angiogenesis inhibitor can be safely and effectively used in combination with cytotoxic anti-cancer agents for treatment of Gastric cancers.

Bacteriophage-eukaryotic cell interaction provides the biological foundation of Phage Display technology, which has been widely adopted in studies involving protein-protein and protein-peptide interactions, and it provides a direct link between the proteins and the DNA encoding them. Phage display has also facilitated the development of new therapeutic agents targeting personalized cancer mutations. Proteins encoded by mutant genes in cancers can be processed and presented on the tumor cell surface by human leukocyte antigen (HLA) molecules, and such mutant peptides are called Neoantigens. Neoantigens are naturally existing tumor markers presented on the cell surface. In clinical settings, the T-cell recognition of neoantigens is the foundation of cancer immunotherapeutics. This year, we utilized phage display to successfully develop the 1st antibody-based neoantigen targeting approach for next-generation personalized cancer therapeutics. In this article, we discussed the strategies for identifying neoantigens, followed by using phage display to create personalized cancer therapeutics-a complete pipeline for personalized cancer treatment.

To systematically review literature exploring experiences of cancer patients regarding their understanding of treatment-focused genomic testing as well as their information needs and related themes.
Six databases were searched for the original studies published in English language that explored patients\' understanding of the information related to the genomic testing and its implications for treatment of cancer. The Mixed-Method Assessement Tool was used to examine the methodological quality of selected articles.
There were 14 studies (5 qualitative and 9 quantitative) that met inclusion and exclusion criteria. The majority of studies revealed that a considerable proportion of cancer patients lacked good undertstanding of treatment-focused genomic testing and wanted to be better informed. Some of the factors associated with poor knowledge about genomic testing were low education, older age, low income, and unemployment. The majority of people with cancer preferred face-to-face communication with their oncologists to discuss and ask questions about genomic testing and treatment. Most also wanted to receive simple, easy to understand written information about treatment-focused genomic testing.
Genomic testing and its implications for treatment emerge as an important aspect of health care across different types of cancer. The evidence indicates that cancer patients want to understand and be well informed about treatment-focused genomic testing in order to be part of decision-making process. Further studies addressing ways to improve cancer patients\' understanding and knowledge of genomic testing are needed.

RESILIENT (CTRI/2018/02/011808) was a single arm, open label, phase II/III study to test if label agnostic therapy regimens guided by Encyclopedic Tumor Analysis (ETA) can offer meaningful clinical benefit for patients with relapsed refractory metastatic (r/r-m) malignancies. Patients with advanced refractory solid organ malignancies where disease had progressed following ≥2 lines of systemic treatments were enrolled in the trial. Patients received personalized treatment recommendations based on integrational comprehensive analysis of freshly biopsied tumor tissue and blood. The primary end points were Objective Response Rate (ORR), Progression Free Survival (PFS) and Quality of Life (QoL). Objective Response (Complete Response + Partial Response) was observed in 54 of 126 patients evaluable per protocol (ORR = 42.9%; 95% CI: 34.3%-51.4%, p < 0.0001). At study completion, Disease Control (Complete Response + Partial Response + Stable Disease) was observed in 114 out of 126 patients evaluable per protocol (CBR = 90.5%; 95% CI: 83.9% - 95.0%, p < 0.00001) and Disease Progression in 12 patients. Median duration of follow-up was 138 days (range 31 to 379). Median PFS at study termination was 134 days (range 31 to 379). PFS rate at 90 days and 180 days were 93.9% and 82.5% respectively. The study demonstrated that tumors have latent vulnerabilities that can be identified via integrational multi-analyte investigations such as ETA. This approach identified viable treatment options that could yield meaningful clinical benefit in this cohort of patients with advanced refractory cancers.

This paper reports the process by which a personalized cancer treatment system was built, following a user-centered approach. We give some background on personalized cancer treatment, the particular tumor chemosensitivity assay supported by the system, as well as some quality and legal issues related to such health systems. We describe how Contextual Design was applied when building the system. Contextual design is a user-centered design technique involving seven steps. We also provide some details about the system implementation. Finally, we explain how the Think-Aloud protocol and Heuristic Evaluation methods were used to evaluate the system and report its results. A qualitative assessment from the users perspective is also provided. Results from the heuristic evaluation indicate that only one of ten heuristics was missing from the system, while five were partially covered and four were fully covered.

The discovery of novel biomarkers that predict treatment response in advanced cancer patients requires acquisition of high-quality tumor samples. As cancer evolves over time, tissue is ideally obtained before the start of each treatment. Preferably, samples are freshly frozen to allow analysis by next-generation DNA/RNA sequencing (NGS) but also for making other emerging systematic techniques such as proteomics and metabolomics possible. Here, we describe the first 469 image-guided biopsies collected in a large collaboration in The Netherlands (Center for Personalized Cancer Treatment) and show the utility of these specimens for NGS analysis.
Image-guided tumor biopsies were performed in advanced cancer patients. Samples were fresh frozen, vital tumor cellularity was estimated, and DNA was isolated after macrodissection of tumor-rich areas. Safety of the image-guided biopsy procedures was assessed by reporting of serious adverse events within 14 days after the biopsy procedure.
Biopsy procedures were generally well tolerated. Major complications occurred in 2.1%, most frequently consisting of pain. In 7.3% of the percutaneous lung biopsies, pneumothorax requiring drainage occurred. The majority of samples (81%) contained a vital tumor percentage of at least 30%, from which at least 500 ng DNA could be isolated in 91%. Given our preset criteria, 74% of samples were of sufficient quality for biomarker discovery. The NGS results in this cohort were in line with those in other groups.
Image-guided biopsy procedures for biomarker discovery to enable personalized cancer treatment are safe and feasible and yield a highly valuable biobank. The Oncologist 2017;22:33-40Implications for Practice: This study shows that it is safe to perform image-guided biopsy procedures to obtain fresh frozen tumor samples and that it is feasible to use these biopsies for biomarker discovery purposes in a Dutch multicenter collaboration. From the majority of the samples, sufficient DNA could be yielded to perform next-generation sequencing. These results indicate that the way is paved for consortia to prospectively collect fresh frozen tumor tissue.

Preclinical research in gynecologic malignancies has largely relied upon cloned cancer-derived cell lines and tumor xenografts derived from these cell lines. Unfortunately, the use of cell lines for translational research has disadvantages because genetic and phenotypic alterations from serial passaging have resulted in expression profiles that are different from the original patient tumors. The patient-derived xenograft (PDX) model derived from human tumor not previously cultured has shown better representation of the heterogeneity of gynecologic malignancies and the human tumor microenvironment with preservation of cytogenetics, cellular complexity, and vascular and stromal tumor architecture. Studies have shown promise with these models to analyze tumor development and adaptation, test drug efficacy, and predict clinical outcomes. Their ultimate value may be seen with preclinical drug screening including novel targeted therapies, biomarker identification, and the development of individualized treatment plans. This article reviews PDX model development, current studies testing chemotherapeutics and targeted therapies, and limitations of the PDX model in gynecologic malignancies.