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Nicholas Borcherding,1– 4 Yogesh Jethava,1,5 Praveen Vikas1,5 1Holden Comprehensive Cancer Center, University of Iowa, College of Medicine, Iowa City, IA, USA; 2Department of Pathology, University of Iowa, College of Medicine, Iowa City, IA, USA; 3Cancer Biology Graduate Program, University of Iowa, College of Medicine, Iowa City, IA, USA; 4Medical Scientist Training Program, University of Iowa, College of Medicine, Iowa City, IA, USA; 5Department of Internal Medicine, University of Iowa, College of Medicine, Iowa City, IA, USACorrespondence: Praveen VikasHolden Comprehensive Cancer Center, 5983 JPP, 200 Hawkins Drive, Iowa City, Iowa 52242, USATel + 1 319-356-2757Email praveen-vikas@uiowa.eduAbstract: The novel coronavirus disease 2019 (COVID-19) pandemic has caused catastrophic damage to human life across the globe along with social and financial hardships. According to the Johns Hopkins University Coronavirus Resource Center, more than 41.3 million people worldwide have been infected, and more than 1,133,000 people have died as of October 22, 2020. At present, there is no available vaccine and a scarcity of efficacious therapies. However, there is tremendous ongoing effort towards identifying effective drugs and developing novel vaccines. Early data from Adaptive COVID-19 Treatment Trials (ACTT) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) and compassionate use study have shown promise for remdesivir, leading to emergency authorization by the Food and Drug Administration (FDA) for treatment of hospitalized COVID-19 patients. However, several randomized studies have now shown no benefit or increased adverse events associated with remdesivir treatment. Drug development is a time-intensive process and requires extensive safety and efficacy evaluations. In contrast, drug repurposing is a time-saving and cost-effective drug discovery strategy geared towards using existing drugs instead of de novo drug discovery. Treatments for cancer and COVID-19 often have similar goals of controlling inflammation, inhibiting cell division, and modulating the host microenvironment to control the disease. In this review, we focus on anti-cancer drugs that can potentially be repurposed for COVID-19 and are currently being tested in clinical trials.Keywords: COVID-19, drug-repurposing, anti-cancer drugs

Kalyan Nadiminti,1 Margarida Silverman,1 Sharathkumar Bhagavathi,2 Praveen Vikas11Division of Hematology and Blood and Marrow Transplantation, University of Iowa Hospital and Clinics, Iowa City, IA, USA; 2Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, USABackground: primary myelofibrosis (PMF) is a myeloproliferative neoplasm which is associated with clonal molecular and cytogenetic abnormalities (CA) and varied clinical manifestations. While various CA have been previously described, t(15; 17) has not been reported in association with this condition.Case presentation: A 69-year-old male presented with constitutional symptoms, cytopenias and bone marrow biopsy revealed immature blasts with fibrosis. Cytogenetic analysis showed a t(15;17) which initially suggested a diagnosis of acute promyelocytic leukemia (APL). However, flourescence in situ hybridization (FISH) and reverse transcriptase polymerase chain reaction (RT-PCR) studies were negative for transcripts promyelocytic leukemia (PML) gene and retinoic acid receptor alpha (RARA) or PML-RARA fusion. Along with these results, a second review of bone marrow histology, flowcytometry and the detection of a calreticulin gene (CALR) mutation helped with the correct diagnosis of PMF. Patient was then treated with ruxolitinib, a JAK (Janus kinase) 1 and 2 inhibitor, and eventually proceeded to receive a matched unrelated reduced intensity conditioning (RIC) allogeneic stem cell transplantation (ASCT) and has been doing well at the 6-month follow up.Conclusions: Our case highlights two points, that the t(15;17) is diagnostic of Acute Promyelocytic Leukemia (APL) in most cases, there are exceptions and it can be associated with other malignancies without causing any APL like features, as noted in this case. Also, that t(15; 17) by itself is never sufficient to diagnose APL without confirmation by other methods and relying solely on cytogenetics without timely confirmatory tests can lead to risks of delay in diagnosis and appropriate management.Keywords: primary myelofibrosis, atypical t(15;17), cytogenetics, FISH, case report

Praveen Vikas,1,2 Nicholas Borcherding,2–5 Weizhou Zhang2–5 1Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City, IA, USA; 2Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA; 3Department of Pathology, College of Medicine, University of Iowa, Iowa City, IA, USA; 4Cancer Biology Graduate Program, College of Medicine, University of Iowa, Iowa City, IA, USA; 5Medical Scientist Training Program, College of Medicine, University of Iowa, Iowa City, IA, USA Abstract: Triple-negative breast cancer (TNBC) is a heterogeneous disease with poorer outcomes compared to other breast cancer subtypes. Contributing to the worse prognosis in TNBC is the higher rates of relapse and rapid progression after relapse. Advances in targeted therapeutics and conventional chemotherapy for TNBC have been stymied due to the lack of specific targets. Moreover, the responses to chemotherapy in TNBC lack durability, partially accounting for the higher rates of relapse. Immunotherapy, notably immune-checkpoint blockade, has shown to improve survival and maintain robust antitumor responses in both hematologic and solid malignancies. Unlike lung cancer, melanoma, and bladder cancer, most breast cancers are not inherently immunogenic and typically have low T cell infiltration. However, among breast cancer subtypes, TNBC is characterized by greater tumor immune infiltrate and higher degree of stromal and intratumoral tumor-infiltrating lymphocytes (TILs), a predictive marker for responses to immunotherapy. Moreover, in TNBC, the high number of stromal TILs is predictive of more favorable survival outcomes and response to chemotherapy. Immunotherapy is being extensively explored in TNBC and clinical trials are showing some promising results. This article focuses on the rationale for immunotherapy in TNBC, to explore and discuss preclinical data, results from early clinical trials, and to summarize some ongoing trials. We will also discuss the potential application of immunotherapy in TNBC from a clinician’s perspective. Keywords: triple-negative breast cancer, immunotherapy, PD-1/PDL-1 antibody, CTLA-4 antibody, checkpoint inhibitors, cancer vaccines