Medicine and Health Sciences Commons^™

Pyrvinium Pamoate: Past, Present, And Future As An Anti-Cancer Drug, Christopher W Schultz, Avinoam Nevler

Department of Surgery Faculty Papers

Pyrvinium, a lipophilic cation belonging to the cyanine dye family, has been used in the clinic as a safe and effective anthelminthic for over 70 years. Its structure, similar to some polyaminopyrimidines and mitochondrial-targeting peptoids, has been linked with mitochondrial localization and targeting. Over the past two decades, increasing evidence has emerged showing pyrvinium to be a strong anti-cancer molecule in various human cancers in vitro and in vivo. This efficacy against cancers has been attributed to diverse mechanisms of action, with the weight of evidence supporting the inhibition of mitochondrial function, the WNT pathway, and cancer stem cell renewal. …

A Machine Learning Model Of Response To Hypomethylating Agents In Myelodysplastic Syndromes, Nathan Radakovich, David A. Sallman, Rena Buckstein, Andrew Brunner, Amy Dezern, Sudipto Mukerjee, Rami Komrokji, Najla Al-Ali, Jacob Shreve, Yazan Rouphail, Anne Parmentier, Alexandre Mamedov, Mohammed Siddiqui, Yihong Guan, Teodora Kuzmanovic, Metis Hasipek, Babal Jha, Jaroslaw P. Maciejewski, Mikkael A. Sekeres, Aziz Nazha

Department of Medical Oncology Faculty Papers

Hypomethylating agents (HMA) prolong survival and improve cytopenias in individuals with higher-risk myelodysplastic syndrome (MDS). Only 30-40% of patients, however, respond to HMAs, and responses may not occur for more than 6 months after HMA initiation. We developed a model to more rapidly assess HMA response by analyzing early changes in patients’ blood counts. Three institutions’ data were used to develop a model that assessed patients’ response to therapy 90 days after the initiation using serial blood counts. The model was developed with a training cohort of 424 patients from2 institutions and validated on an independent cohort of 90 patients. …

Cancer-Specific Survival After Diagnosis In Men Versus Women: A Pan-Cancer Analysis., Yan He, Yonglin Su, Junsong Zeng, Weelic Chong, Xiaolin Hu, Yu Zhang, Xingchen Peng

Department of Medical Oncology Faculty Papers

Comprehensive understanding of cancer-specific survival differences in gender is critical for cancer prevention and treatment. Based on the Surveillance Epidemiology and End Results database, we included data from the most prevalent cancers (lung, esophageal, liver, pancreatic, stomach, colorectal, kidney, and bladder cancer). Cox proportional hazards regression models were constructed to estimate hazard ratios, simultaneously adjusting for demographic, clinical, and treatment factors. Overall, male patients had a worse cancer-specific survival than female patients. After adjustment for cancer prevalence with 1:1 matching, gender remained a significant factor in cancer-specific survival. Among the included cancer types, female patients showed survival benefit in lung, …

Advanced-Stage Melanoma At Presentation Following The Peak Of The Pandemic: A Covid-19 Cancer Canary In A Coal Mine, Ryan Lamm, Md, Walker Lyons, Md, Winnie So, Rn, Alliric I. Willis, Md, Facs, Msph

Department of Surgery Faculty Papers

Background: For melanoma patients, timely identification and tumor thickness are directly correlated with outcomes. COVID-19 impacted both patients' ability and desire to see physicians. We sought to identify whether the pandemic correlated with changes in melanoma thickness at presentation and subsequent treatment timeline.

Methods: Retrospective chart review was performed on patients who underwent surgery for melanoma in an academic center surgical oncology practice from May 2019 to September 2021. Patients were split into two cohorts: "pre-pandemic" from May 2019 to May 2020 and "pandemic," after May 2020, representing when these patients received their initial diagnostic biopsy. Demographic and melanoma-specific variables …

The Future Of Targeted Kinase Inhibitors In Melanoma, Signe Caksa, Usman Baqai, A E Aplin

Department of Cancer Biology Faculty Papers

Melanoma is a cancer of the pigment-producing cells of the body and its incidence is rising. Targeted inhibitors that act against kinases in the MAPK pathway are approved for BRAF-mutant metastatic cutaneous melanoma and increase patients' survival. Response to these therapies is limited by drug resistance and is less durable than with immune checkpoint inhibition. Conversely, rare melanoma subtypes have few therapeutic options for advanced disease and MAPK pathway targeting agents show minimal anti-tumor effects. Nevertheless, there is a future for targeted kinase inhibitors in melanoma: in new applications such as adjuvant or neoadjuvant therapy and in novel combinations with …

Challenges And Opportunities For Immunotherapeutic Intervention Against Myeloid Immunosuppression In Glioblastoma, Mark A Exley, Samantha Garcia, Amelia Zellander, Jenny Zilberberg, David W. Andrews

Department of Neurosurgery Faculty Papers

Glioblastoma multiforme (GBM), the most common and deadly brain cancer, exemplifies the paradigm that cancers grow with help from an immunosuppressive tumor microenvironment (TME). In general, TME includes a large contribution from various myeloid lineage-derived cell types, including (in the brain) altered pathogenic microglia as well as monocyte-macrophages (Macs), myeloid-derived suppressor cells (MDSC) and dendritic cell (DC) populations. Each can have protective roles, but has, by definition, been coopted by the tumor in patients with progressive disease. However, evidence demonstrates that myeloid immunosuppressive activities can be reversed in different ways, leading to enthusiasm for this therapeutic approach, both alone and …

Dna-Pkcs: A Targetable Protumorigenic Protein Kinase., Emanuela Dylgjeri, Karen E Knudsen

Department of Cancer Biology Faculty Papers

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a pleiotropic protein kinase that plays critical roles in cellular processes fundamental to cancer. DNA-PKcs expression and activity are frequently deregulated in multiple hematologic and solid tumors and have been tightly linked to poor outcome. Given the potentially influential role of DNA-PKcs in cancer development and progression, therapeutic targeting of this kinase is being tested in preclinical and clinical settings. This review summarizes the latest advances in the field, providing a comprehensive discussion of DNA-PKcs functions in cancer and an update on the clinical assessment of DNA-PK inhibitors in cancer therapy.

Risk Factors For Hospitalizations Among Older Adults With Gastrointestinal Cancers, Daneng Li, Can-Lan Sun, Rebecca Allen, Christiana J Crook, Abrahm Levi, Richard Ballena, Heidi D Klepin, Rawad Elias, Supriya G Mohile, William P Tew, Cynthia Owusu, Hyman B Muss, Stuart M Lichtman, Cary P Gross, Andrew Chapman, Ajeet Gajra, Harvey J Cohen, Vani Katheria, Arti Hurria, William Dale

Department of Medical Oncology Faculty Papers

Background: Older adults (≥65 years) with gastrointestinal (GI) cancers who receive chemotherapy are at increased risk of hospitalization caused by treatment-related toxicity. Geriatric assessment (GA) has been previously shown to predict risk of toxicity in older adults undergoing chemotherapy. However, studies incorporating the GA specifically in older adults with GI cancers have been limited. This study sought to identify GA-based risk factors for chemotherapy toxicity-related hospitalization among older adults with GI cancers.

Patients and methods: We performed a secondary post hoc subgroup analysis of two prospective studies used to develop and validate a GA-based chemotherapy toxicity score. The incidence of …