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Cancer is primarily a disease of the elderly, but there is a disproportionate lack of data from clinical trials in this population. Oncologists tend to underdiagnose and undertreat geriatric patients with cancer, leading to poor survival outcomes. New therapies or therapeutic combinations such as immunotherapy and stereotactic body radiation therapy (SBRT) can be used in the elderly for better tumor control and survival, with fewer toxicities. The aim of this review is to describe the synergistic effects of immunotherapy and radiation therapy (RT) and to discuss the use of these therapies concurrently and/or sequentially in the elderly. To gain a fuller picture of their elderly patients health, physicians may also consider incorporating a comprehensive geriatric assessment (CGA) to evaluate their functional capacity, cognition, physical and mental health, and social supports which we will discuss in this review. It is recommended that oncologists use geriatric assessments in their everyday practice to have better insight on their complex elderly patients, therefore providing them a higher quality of care. They should also be incorporated in clinical trials as a way to assess and include more elderly patients in the study. Ultimately, the elderly deserve to be treated with more than their chronological age in mind, and new combination therapies and use of a geriatric assessment can help achieve that.

Radiation therapy remains at the center of head and neck cancer treatment. With improvements in treatment delivery, radiation therapy has become an affective ablative modality for head and neck cancers. Immune checkpoint inhibitors are now also playing a more active role both in the locally advanced and metastatic setting. With improved systemic options, local noninvasive modalities including radiation therapy are playing a critical role in overcoming resistance in head and neck cancer. The aim of this review is to describe the role of radiation therapy in modulating the tumor microenvironment and how radiation dose, fractionation and treatment field can impact the immune system and potentially effect outcomes when combined with immunotherapy. The review will encompass several common scenarios where radiation is used to improve outcomes and overcome potential resistance that may develop with immunotherapy in head and neck squamous cell carcinoma (HNSCC), including upfront locally advanced disease receiving definitive radiation and recurrent disease undergoing re-irradiation. Lastly, we will review the potential toxicities of combined therapy and future directions of their role in the management of HNSCC.

Triple-negative breast cancer (TNBC) occurs in 10-15% of all breast cancer patients, yet it accounts for about half of all breast cancer deaths. There is an urgent need to identify new antitumor targets to provide additional treatment options for patients afflicted with this aggressive disease. Preclinical evidence suggests a critical role for insulin-like growth factor-2 (IGF2) and androgen receptor (AR) in regulating TNBC progression. To advance this work, a panel of TNBC cell lines was investigated with all cell lines showing significant expression of IGF2. Treatment with IGF2 stimulated cell proliferation in vitro (p < 0.05). Importantly, combination treatments with IGF1R inhibitors BMS-754807 and NVP-AEW541 elicited significant inhibition of TNBC cell proliferation (p < 0.001). Based on Annexin-V binding assays, BMS-754807, NVP-AEW541 and enzalutamide induced TNBC cell death (p < 0.005). Additionally, combination of enzalutamide with BMS-754807 or NVP-AEW541 exerted significant reductions in TNBC proliferation even in cells with low AR expression (p < 0.001). Notably, NVP-AEW541 and BMS-754807 reduced AR levels in BT549 TNBC cells. These results provide evidence that IGF2 promotes TNBC cell viability and proliferation, while inhibition of IGF1R/IR and AR pathways contribute to blockade of TNBC proliferation and promotion of apoptosis in vitro.

The time-consuming process of manual contouring of healthy tissue and organs in radiation therapy has prompted the development of computational systems to aid and automate this process, such as artificial intelligence (AI) segmentation and interpolation algorithms. These algorithms are useful in saving time, however, they are not always accurate. Fixing such inaccuracies by editing contours is a manual, time-consuming process as no 'undo' feature currently exists in the most commonly used treatment planning system (TPS). In this short technical report, we present our script for automated de-interpolation to enable faster editing of contours to streamline the adoption of AI-assisted methodologies to enhance clinical workflow., Competing Interests: Human subjects: All authors have confirmed that this study did not involve human participants or tissue. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: Colin Yeo was a fellow in the USC/CHLA Summer Oncology Research Fellowship (SORF) Program, supported in part by the National Cancer Institute of the National Institutes of Health under Award Number R25CA225513 and by the Norris Comprehensive Cancer Center in Los Angeles, Children’s Hospital Los Angeles, Concern Foundation for Cancer Research, Curing Kids Cancer, and Tri Delta. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health., (Copyright © 2024, Karnwal et al.)

Phage display is a powerful technique for rapid construction and screening of peptide libraries with over 10 9 sequence diversity. The M13 bacteriophage genome can be edited to incorporate randomized amino acids, which will be displayed on its minor coat protein (pIII). To enable screening of nonnatural cyclic peptides on phage, the minor coat protein can be modified with a chemical cross-linker. By taking advantage of the nucleophilicity and low abundance of free cysteines on phage, a variety of cysteine cross-linkers can be installed on the pIII protein. Here, we describe the construction of a chemically modified cyclic phage library through a cysteine cross-linking reagent, 1,3-dichloroacetone (DCA)., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)