Regulation of volume-regulated anion channels alters sensitivity to platinum chemotherapy.

Cisplatin-based chemotherapy is used across many common tumor types, but resistance reduces the likelihood of long-term survival. We previously found the puromycin-sensitive aminopeptidase, NPEPPS, as a druggable driver of cisplatin resistance in vitro and in vivo and in patient-derived organoids. Here, we present a general mechanism where NPEPPS interacts with the volume-regulated anion channels (VRACs) to control cisplatin import into cells and thus regulate cisplatin response across a range of cancer types.

Inauspicious Beginnings: Cancer and Financial Hardship among Children, Adolescents, and Young Adults in the United States.

With the release of the American Association of Cancer Research Cancer Progress Report 2024, we address two aspects of cancer and its treatment in younger age groups addressed in the progress report: first, the chronicity of financial hardship and second, inequities that burden the totality of society and hinder progress of scientific advances in cancer control and treatment. Financial hardship for younger age groups diagnosed with cancer causes lasting financial damage to both the patients and their families. Advancements in new technologies and treatments that improve survival may not be as effective if they are unaffordable or will cause lasting financial distress.

Financial Difficulty Over Time in Young Adults With Breast Cancer.

Importance: Young adults aged 18 to 39 years represent the minority of breast cancer diagnoses but are particularly vulnerable to financial hardship. Factors contributing to sustained financial hardship are unknown.

Objectives: To identify financial hardship patterns over time and characterize factors associated with discrete trajectories; it was hypothesized that treatment-related arm morbidity, a key source of expense, would be associated with long-term financial difficulty.

DNA-PK inhibition enhances neoantigen diversity and increases T cell responses to immunoresistant tumors.

Effective antitumor T cell activity relies on the expression and MHC presentation of tumor neoantigens. Tumor cells can evade T cell detection by silencing the transcription of antigens or by altering MHC machinery, resulting in inadequate neoantigen-specific T cell activation. We identified the DNA-protein kinase inhibitor (DNA-PKi) NU7441 as a promising immunomodulator that reduced immunosuppressive proteins, while increasing MHC-I expression in a panel of human melanoma cell lines.

A distinct metabolic and epigenetic state drives trained immunity in HSC-derived macrophages from autoimmune mice.

Here, we investigate the contribution of long-term hematopoietic stem cells (HSCs) to trained immunity (TI) in the setting of chronic autoimmune disease. Using a mouse model of systemic lupus erythematosus (SLE), we show that bone marrow-derived macrophages (BMDMs) from autoimmune mice exhibit hallmark features of TI, including increased Mycobacterium avium killing and inflammatory cytokine production, which are mechanistically linked to increased glycolytic metabolism. We show that HSCs from autoimmune mice constitute a transplantable, long-term reservoir for macrophages that exhibit the functional properties of TI.

Engaging Oncology and Occupational Medicine to Inform Design of a Total Worker Health® Intervention to Address Employment, Financial, and Well-being Outcomes in Cancer Survivors.

Objectives: Few Total Worker Health ® studies and fewer interventions examine well-being in the work context of cancer survivorship. We investigated the possibility of occupation and oncology professionals working together to address employed survivors' work-associated needs.

Methods: We employed a community-based participatory research approach to examine the educational, contextual, and workflow needs of oncology care team members to inform intervention design.

Long-term Musculoskeletal Consequences of Chemotherapy in Pediatric Mice.

Thanks to recent progress in cancer research, most children treated for cancer survive into adulthood. Nevertheless, the long-term consequences of anticancer agents are understudied, especially in the pediatric population. We and others have shown that routinely administered chemotherapeutics drive musculoskeletal alterations, which contribute to increased treatment-related toxicity and long-term morbidity.

Final outcomes analysis of the cell product SQZ-PBMC-HPV Phase 1 trial in incurable HPV16+ solid tumors shows improved overall survival in patients with increased CD8+ T cell tumor infiltration.

Cancer vaccines strive to induce robust, antigen-targeted, T-cell-mediated immune responses but have struggled to produce meaningful regression in solid tumors. An autologous cell vaccine, SQZ-PBMC-HPV, was developed by SQZ Biotechnologies using microfluidic squeezing technology to load PBMCs with HPV16 E6 and E7 antigens in HLA-A*02+ patients. The SQZ-PBMC-HPV-101 Phase 1 trial (NCT04084951) enrolled patients with incurable HPV16+ cancers.

Cancer diagnosis and treatment in working-age adults: Implications for employment, health insurance coverage, and financial hardship in the United States.

The rising costs of cancer care and subsequent medical financial hardship for cancer survivors and families are well documented in the United States. Less attention has been paid to employment disruptions and loss of household income after a cancer diagnosis and during treatment, potentially resulting in lasting financial hardship, particularly for working-age adults not yet age-eligible for Medicare coverage and their families. In this article, the authors use a composite patient case to illustrate the adverse consequences of cancer diagnosis and treatment for employment, health insurance coverage, household income, and other aspects of financial hardship.

A phase 1 study of triple-targeted therapy with BRAF, MEK, and AKT inhibitors for patients with BRAF-mutated cancers.

Background: Aberrant PI3K/AKT signaling in BRAF-mutant cancers contributes to resistance to BRAF inhibitors. The authors examined dual MAPK and PI3K pathway inhibition in patients who had BRAF-mutated solid tumors (ClinicalTrials.gov identifier NCT01902173).

Patient-Reported Outcomes in Patients With Advanced Urothelial Cancer Who Are Ineligible for Cisplatin and Treated With First-Line Enfortumab Vedotin Alone or With Pembrolizumab.

Purpose: Locally advanced/metastatic urothelial cancer (la/mUC) affects patients' quality of life (QOL) and functioning. We describe the impact of first-line (1L) enfortumab vedotin (EV) alone or with pembrolizumab (P) on QOL/functioning/symptoms in patients with la/mUC who were cisplatin-ineligible from EV-103 Cohort K.

Methods: In this phase Ib/II trial, patients were randomly assigned 1:1 to EV + P or EV monotherapy (mono).

Implementation science for cancer control: One center's experience addressing context, adaptation, equity, and sustainment.

Implementation science (IS) has great potential to enhance the frequency, speed, and quality of the translation of evidence-based programs, policies, products, and guidelines into practice. Progress has been made, but with some notable exceptions, this promise has not been achieved for cancer prevention and control. We discuss five interrelated but conceptually distinct, crosscutting issues important to accelerate IS for cancer prevention and control and how our Colorado Implementation Science Center in Cancer Control (COISC3) addressed these issues.

Much work to do about measuring work.

Work ability is a critical economic and well-being indicator in cancer care. Yet, work ability is understudied in clinical trials and observational research and is often undocumented in medical records. Despite agreement on the importance of work from well-being, health insurance, and financial perspectives, standardized approaches for collecting, measuring, and analyzing work outcomes are lacking in the health-care setting.

Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression.

Immune escape is a prerequisite for tumor growth. We previously described a decline in intratumor activated cytotoxic T cells and T cell receptor (TCR) clonotype diversity in invasive breast carcinomas compared to ductal carcinoma in situ (DCIS), implying a central role of decreasing T cell responses in tumor progression. To determine potential associations between peripheral immunity and breast tumor progression, here, we assessed the peripheral blood TCR clonotype of 485 breast cancer patients diagnosed with either DCIS or de novo stage IV disease at younger (<45) or older (≥45) age.

A plain language summary exploring a new treatment combination for untreated locally advanced or metastatic urothelial cancer: enfortumab vedotin plus pembrolizumab.

What Is This Summary About?: This summary provides the results of a study of two treatments for cancer, enfortumab vedotin and pembrolizumab, that were studied together against locally advanced or metastatic urothelial cancer (la/mUC), a cancer that occurs most commonly in the bladder.

What Were The Results?: In the 45 patients studied, around 16% did have serious side effects, but most side effects were manageable. Twenty-four percent of patients, however, stopped the study treatment because of their side effects.

Conception and pregnancy among women with a live birth after breast cancer treatment: A survey study of young breast cancer survivors.

Background: Breast cancer (BC) is the most common malignancy in women of reproductive age. This study sought to explore the postcancer conception and pregnancy experience of young BC survivors to inform counseling.

Methods: In the Young Women's Breast Cancer Study (NCT01468246), a multicenter, prospective cohort, participants diagnosed at age ≤40 years with stage 0-III BC who reported ≥1 postdiagnosis live birth were sent an investigator-developed survey.