The Transcriptional and Epigenetic Landscape of Cancer Cell Lineage Plasticity.

Unlabelled: Lineage plasticity, a process whereby cells change their phenotype to take on a different molecular and/or histologic identity, is a key driver of cancer progression and therapy resistance. Although underlying genetic changes within the tumor can enhance lineage plasticity, it is predominantly a dynamic process controlled by transcriptional and epigenetic dysregulation. This review explores the transcriptional and epigenetic regulators of lineage plasticity and their interplay with other features of malignancy, such as dysregulated metabolism, the tumor microenvironment, and immune evasion.

Modular synthesis of clickable peptides via late-stage maleimidation on C(7)-H tryptophan.

Cyclic peptides have attracted tremendous attention in the pharmaceutical industry owing to their excellent cell penetrability, stability, thermostability, and drug-like properties. However, the currently available facile methodologies for creating such peptides are rather limited. Herein, we report an efficient and direct peptide cyclization via rhodium(III)-catalyzed C(7)-H maleimidation.

Serendipity Strikes: How Pursuing Novel Hypotheses Shifted the Paradigm Regarding the Genetic Basis of Colorectal Cancer and Changed Cancer Therapy.

In this installment of the "Paradigm Shifts in Perspective" series, the authors, all scientists who have been involved in colorectal cancer (CRC) research for most or all of their careers, have watched the field develop from early pathological descriptions of tumor formation to the current understanding of tumor pathogenesis that informs personalized therapies. We outline how our understanding of the pathogenetic basis of CRC began with seemingly isolated discoveries-initially with the mutations in RAS and the APC gene, the latter of which was initially found in the context of intestinal polyposis, to the more complex process of multistep carcinogenesis, to the chase for tumor suppressor genes, which led to the unexpected discovery of microsatellite instability (MSI). These discoveries enabled the authors to better understand how the DNA mismatch repair (MMR) system not only recognizes DNA damage but also responds to damage by DNA repair or by triggering apoptosis in the injured cell.

Correction: Multiplexed molecular imaging with surface enhanced resonance Raman scattering nanoprobes reveals immunotherapy response in mice multichannel image segmentation.

Correction for 'Multiplexed molecular imaging with surface enhanced resonance Raman scattering nanoprobes reveals immunotherapy response in mice multichannel image segmentation' by Chrysafis Andreou , , 2022, , 1540-1552, https://doi.org/10.1039/d2nh00331g.

Impact of a novel multilayer imager on metal artifacts in MV-CBCT.

. Megavoltage cone-beam computed tomography (MV-CBCT) imaging offers several advantages including reduced metal artifacts and accurate electron density mapping for adaptive or emergent situations. However, MV-CBCT imaging is limited by the poor efficiency of current detectors.

DYRK1A promotes viral entry of highly pathogenic human coronaviruses in a kinase-independent manner.

Identifying host genes essential for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has the potential to reveal novel drug targets and further our understanding of Coronavirus Disease 2019 (COVID-19). We previously performed a genome-wide CRISPR/Cas9 screen to identify proviral host factors for highly pathogenic human coronaviruses. Few host factors were required by diverse coronaviruses across multiple cell types, but DYRK1A was one such exception.

Analysis of Breast Cancer Family History, Estrogen Receptor Status, and Breast Cancer Outcomes in Sweden.

Importance: Breast cancer (BC), the most prevalent cancer among women globally, is a heterogeneous disease, with prognosis differing by estrogen receptor (ER) status. Having a family history of BC increases the risk of BC; however, it is unclear whether family history is associated with the prognosis of overall and ER-specific BC.

Objective: To assess whether a family history of BC is associated with the prognosis of overall and ER-specific BC.

Phase 2 trial of palbociclib and ganitumab in patients with relapsed Ewing sarcoma.

Background: Ewing sarcoma (EWS) is an aggressive sarcoma with few treatment options for patients with relapsed disease. Cyclin-dependent kinase 4 (CDK4) is a genomic vulnerability in EWS that is synergistic with IGF-1R inhibition in preclinical studies. We present the results of a phase 2 study combining palbociclib (CDK4/6 inhibitor) with ganitumab (IGF-1R monoclonal antibody) for patients with relapsed EWS.

Bayesian risk prediction model for colorectal cancer mortality through integration of clinicopathologic and genomic data.

Routine tumor-node-metastasis (TNM) staging of colorectal cancer is imperfect in predicting survival due to tumor pathobiological heterogeneity and imprecise assessment of tumor spread. We leveraged Bayesian additive regression trees (BART), a statistical learning technique, to comprehensively analyze patient-specific tumor characteristics for the improvement of prognostic prediction. Of 75 clinicopathologic, immune, microbial, and genomic variables in 815 stage II-III patients within two U.

Plasma 25-Hydroxyvitamin D Levels and Survival in Stage III Colon Cancer: Findings from CALGB/SWOG 80702 (Alliance).

Purpose: To assess whether higher plasma 25-hydroxyvitamin D [25(OH)D] is associated with improved outcomes in colon cancer and whether circulating inflammatory cytokines mediate such association.

Experimental Design: Plasma samples were collected from 1,437 patients with stage III colon cancer enrolled in a phase III randomized clinical trial (CALGB/SWOG 80702) from 2010 to 2015, who were followed until 2020. Cox regressions were used to examine associations between plasma 25(OH)D and disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR).

Circulating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma.

Renal cell carcinoma (RCC) of variant histology comprises approximately 20% of kidney cancer diagnoses, yet the optimal therapy for these patients and the factors that impact immunotherapy response remain largely unknown. To better understand the determinants of immunotherapy response in this population, we characterized blood- and tissue-based immune markers for patients with variant histology RCC, or any RCC histology with sarcomatoid differentiation, enrolled in a phase II clinical trial of atezolizumab and bevacizumab. Baseline circulating (plasma) inflammatory cytokines were highly correlated with one another, forming an "inflammatory module" that was increased in International Metastatic RCC Database Consortium poor-risk patients and was associated with worse progression-free survival (PFS; P = 0.

Pre-existing immunity does not impair the engraftment of CRISPR-Cas9-edited cells in rhesus macaques conditioned with busulfan or radiation.

CRISPR-Cas9-based therapeutic genome editing approaches hold promise to cure a variety of human diseases. Recent findings demonstrate pre-existing immunity for the commonly used Cas orthologs from (SpCas9) and (SaCas9) in humans, which threatens the success of this powerful tool in clinical use. Thus, a comprehensive investigation and potential risk assessment are required to exploit the full potential of the system.

The gut microbiome modifies the associations of short- and long-term physical activity with body weight changes.

Background: The gut microbiome regulates host energy balance and adiposity-related metabolic consequences, but it remains unknown how the gut microbiome modulates body weight response to physical activity (PA).

Methods: Nested in the Health Professionals Follow-up Study, a subcohort of 307 healthy men (mean[SD] age, 70[4] years) provided stool and blood samples in 2012-2013. Data from cohort long-term follow-ups and from the accelerometer, doubly labeled water, and plasma biomarker measurements during the time of stool collection were used to assess long-term and short-term associations of PA with adiposity.

Risk of estrogen receptor-specific breast cancer by family history of estrogen receptor subtypes and other cancers.

Background: The extent to which the risk of estrogen receptor (ER)-specific breast cancer is associated with ER status of breast cancer and other cancers among first-degree relatives is unclear.

Methods: This population-based cohort included 464 707 cancer-free women in Stockholm, Sweden, during 1978-2019. For ER-negative and ER-positive breast cancers, we estimated hazard ratios (HRs) associated with ER status of female first-degree relatives with breast cancer and of other cancers in all first-degree relatives.

Antibody-Drug Conjugates in Lung Cancer: Recent Advances and Implementing Strategies.

Antibody-drug conjugates (ADCs) are one of the fastest-growing oncology therapeutics, merging the cytotoxic effect of conjugated payload with the high specific ability and selectivity of monoclonal antibody targeted on a specific cancer cell membrane antigen. The main targets for ADC development are antigens commonly expressed by lung cancer cells, but not in normal tissues. They include human epidermal growth factor receptor 2, human epidermal growth factor receptor 3, trophoblast cell surface antigen 2, c-MET, carcinoembryonic antigen-related cell adhesion molecule 5, and B7-H3, each with one or more specific ADCs that showed encouraging results in the lung cancer field, more in non-small-cell lung cancer than in small-cell lung cancer histology.

The SWI/SNF chromatin-remodeling subunit DPF2 facilitates NRF2-dependent antiinflammatory and antioxidant gene expression.

During emergency hematopoiesis, hematopoietic stem cells (HSCs) rapidly proliferate to produce myeloid and lymphoid effector cells, a response that is critical against infection or tissue injury. If unresolved, this process leads to sustained inflammation, which can cause life-threatening diseases and cancer. Here, we identify a role of double PHD fingers 2 (DPF2) in modulating inflammation.

Neurocognitive outcomes in adult survivors of neuroblastoma: A report from the Childhood Cancer Survivor Study.

Background: Despite survival improvements, there is a paucity of data on neurocognitive outcomes in neuroblastoma survivors. This study addresses this literature gap.

Methods: Neurocognitive impairments in survivors were compared to sibling controls from the Childhood Cancer Survivor Study (CCSS) using the CCSS Neurocognitive Questionnaire.

Evolution of Therapeutic Benefit Measurement Criteria in Myelodysplastic Syndromes/Neoplasms.

Myelodysplastic syndromes/neoplasms (MDS) are heterogeneous, clonal myeloid neoplasms characterized by ineffective hematopoiesis, progressive cytopenias, and an increased risk of progression to acute myeloid leukemia. The diversity in disease severity, morphology, and genetic landscape challenges not only novel drug development but also therapeutic response assessment. The MDS International Working Group (IWG) response criteria were first published in the year 2000 focusing on measures of blast burden reduction and hematologic recovery.

Spectrum From Clonal Hematopoiesis to Myelodysplastic Neoplasm/Syndromes and Other Myeloid Neoplasms.

Clonal hematopoiesis (CH) confers a high risk of aging-related diseases and hematologic malignancy. There are still significant knowledge gaps in identifying high-risk patients with CH and managing such patients. In this review, we focus on 3 areas: (1) the natural history of CH; (2) the risks of progression of CH, including CH of indeterminate potential, clonal cytopenia of undetermined significance, and therapy-related CH, to myeloid malignancy; and (3) the challenges and unmet needs of CH management and research.

Cumulative burden of late, major surgical intervention in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study (CCSS) cohort.

Background: Multimodal cancer therapy places childhood cancer survivors at increased risk for chronic health conditions, subsequent malignancies, and premature mortality as they age. We aimed to estimate the cumulative burden of late (>5 years from cancer diagnosis), major surgical interventions among childhood cancer survivors, compared with their siblings, and to examine associations between specific childhood cancer treatments and the burden of late surgical interventions.

Methods: We analysed data from the Childhood Cancer Survivor Study (CCSS), a retrospective cohort study with longitudinal prospective follow-up of 5-year survivors of childhood cancer (diagnosed before age 21 years) treated at 31 institutions in the USA, with a comparison group of nearest-age siblings of survivors selected by simple random sampling.

COVID-19 and Other Viral Infections in Patients With Hematologic Malignancies.

COVID-19 and our armamentarium of strategies to combat it have evolved dramatically since the virus first emerged in late 2019. Vaccination remains the primary strategy to prevent severe illness, although the protective effect can vary in patients with hematologic malignancy. Strategies such as additional vaccine doses and now bivalent boosters can contribute to increased immune response, especially in the face of evolving viral variants.