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2021 ACMT Annual Scientific Meeting Abstracts-Virtual.

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Unraveling the Anti-Cancer Mechanisms of Antibiotics: Current Insights, Controversies, and Future Perspectives.

Cancer persists as a significant global health challenge, claiming millions of lives annually despite remarkable strides in therapeutic innovation. Challenges such as drug resistance, toxicity, and suboptimal efficacy underscore the need for novel treatment paradigms. In this context, the repurposing of antibiotics as anti-cancer agents has emerged as an attractive prospect for investigation. Diverse classes of antibiotics have exhibited promising anti-cancer properties in both in vitro and in vivo studies. These mechanisms include the induction of apoptosis and cell cycle arrest, generation o

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… However, anthracyclines, particularly doxorubicin, are notorious for their cardiotoxic effects, which are attributed to their impact on inflammation, oxidative stress, apoptosis, and mitochondrial dysfunction in myocardial cells [ 13 ]. … Anthracyclines: Molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev. 2004;56:185–229. doi: 10.1124/pr.56.2.6. 12. Cortés-Funes H., Coronado C. Role of anthracyclines in the era of targeted therapy. Cardiovasc. …

Optimal Delivery of Follow-Up Care After Allogeneic Hematopoietic Stem-Cell Transplant: Improving Patient Outcomes with a Multidisciplinary Approach.

The increasing indications for allogeneic stem-cell transplant in patients with hematologic malignancies and non-malignant diseases combined with improved clinical outcomes have contributed to increase the number of long-term survivors. However, survivors are at increased risk of developing a unique set of complications and late effects, besides graft-versus-host disease and disease relapse. In this setting, the management capacity of a single health-care provider can easily be overwhelmed. Thus, to provide appropriate survivorship care, a multidisciplinary approach for the long-term follow-up

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… Younger and older patients at the time of administration, as well as females, seem to have the higher risk of anthracycline-induced cardiotoxicity. … Treatment-related cardiotoxicity in survivors of childhood cancer. Nat Rev Clin Oncol . 2013;10(12):697–710. doi: 10.1038/nrclinonc.2013.195 39. Chow EJ, Wong K, Lee SJ, et al. Late cardiovascular complications after hematopoietic cell transplantation. …

Safety and Tolerability of Antibody-Drug Conjugates in Cancer.

Antibody-drug conjugates are monoclonal antibodies attached to biologically active drugs through chemical linkers that deliver and release cytotoxic agents at the tumor site, reducing the likelihood of systemic exposure and therefore toxicity. Currently, there are about 110 ongoing studies implementing antibody-drug conjugates in the treatment of multiple human malignancies. Antibody-drug conjugates carry a feature of the specificity of a monoclonal antibody and the anti-neoplastic potential of a cytotoxin. The first antibody-drug conjugate was approved in 2001, and the field of antibody-drug

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… Some other less prevalent but serious AEs, including pulmonitis, hepatotoxicity, and cardiotoxicity, were rare in both arms and were managed with BV dose modifications or discontinuations. Very few patients with comorbidities or risk factors developed secondary malignancies. … A retrospective study of 246 patients treated with trastuzumab revealed a LVEF decline ≥ 10% in 13% of patients, ≥ 20% decline in 4.5% of cases within 1 year after trastuzumab initiation. [ 48 ] Trastuzumab was discontinued because of suspected cardiotoxicity in 2.4% of patients. …

Position Statement on the Use of Myocardial Strain in Cardiology Routines by the Brazilian Society of Cardiology's Department Of Cardiovascular Imaging - 2023.

Central Illustration : Position Statement on the Use of Myocardial Strain in Cardiology Routines by the Brazilian Society of Cardiology's Department Of Cardiovascular Imaging - 2023 Proposal for including strain in the integrated diastolic function assessment algorithm, adapted from Nagueh et al.67 Am: mitral A-wave duration; Ap: reverse pulmonary A-wave duration; DD: diastolic dysfunction; LA: left atrium; LASr: LA strain reserve; LVGLS: left ventricular global longitudinal strain; TI: tricuspid insufficiency. Confirm concentric remodeling with LVGLS. In LVEF, mitral E wave deceleration time

Gastrointestinal toxicities of proteasome inhibitor therapy.

PurposeProteasome inhibitors (PIs), which cause cell death via tumor suppressor and pro-apoptotic proteins, are integral to treatment of many hematologic malignancies but are limited by their gastrointestinal adverse effects. Evidence regarding these PI-related adverse effects is scant. In this study, we evaluated gastrointestinal adverse events caused by PIs and compared gastrointestinal toxicities between bortezomib, carfilzomib, and ixazomib.MethodsWe conducted a retrospective study of cancer patients treated with PIs at a tertiary care cancer center to investigate the clinical characterist

Efficacy and Safety of Ixazomib Plus Lenalidomide and Dexamethasone Following Injectable PI-Based Therapy in Relapsed/Refractory Multiple Myeloma.

This nationwide, multicenter, open-label, single-arm study evaluated the efficacy and safety of the oral proteasome inhibitor (PI), ixazomib plus lenalidomide (LEN) and dexamethasone (DEX) (IRd) following injectable PI-based therapy for relapsed/refractory multiple myeloma (RRMM). Of 45 patients enrolled, 36 patients received IRd after achieving at least a minor response to 3 cycles of bortezomib or carfilzomib plus LEN + DEX (VRd, n=6; KRd, n=30). At median follow-up of 20.8 months, the 12-month event-free survival rate (primary endpoint) was 49% (90% CI: 35.9-62.0), counting 11 events of pro

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… Both bortezomib and carfilzomib are associated with the development of peripheral neuropathy [ 6 ] and cardiotoxicity [ 7 ], which are related to cumulative dose. … Discussion This nationwide, multicenter, open-label, single-arm study was designed to control patients' disease early in treatment with three cycles of injected PI, reduce side effects such as peripheral neuropathy and cardiotoxicity, and reduce the burden of long-term parenteral therapy. …

Effects of hsa-miR-28-5p on Adriamycin Sensitivity in Diffuse Large B-Cell Lymphoma.

BackgroundAdriamycin (doxorubicin) is an important traditional drug that exhibits cytotoxicity in Diffuse Large B-cell Lymphoma (DLBCL). Doxorubicin affects the DLBCL cells at all stages of their cell cycle. Combined with our previous results, this study discovered that the overexpression of hsa-miR-28-5p inhibited the proliferation, promoted apoptosis, and triggered cell cycle arrest at the S-phase in DLBCL cells. However, the effect of (Homo sapiens, hsa)-microRNA (miR)-28-5p on doxorubicin sensitivity in DLBCL has not been investigated. This study aims to reveal the effects of hsa-miR-28-5p

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… Doxorubicin-induced apoptosis: implications in cardiotoxicity. Molecular and Cellular Biochemistry . 2002;234/235(1):119–124. doi: 10.1023/a:1015976430790. 12. Minotti G., Menna P., Salvatorelli E., Cairo G., Gianni L. … Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacological Reviews . 2004;56(2):185–229. doi: 10.1124/pr.56.2.6. 13. Lim E. L., Trinh D. L., Scott D. W., et al. …

Case series discussion of cardiac and vascular events following carfilzomib treatment: possible mechanism, screening, and monitoring.

BackgroundCarfilzomib is a selective proteasome inhibitor approved in the United States in 2012 for the treatment of relapsed and refractory multiple myeloma. Although cardiopulmonary and vascular events have been reported infrequently, they can be potentially serious complications, and their incidence and pathophysiology following carfilzomib treatment remain poorly characterized in a real-world patient population.MethodsWe retrospectively reviewed the records of 67 patients with relapsed and/or refractory multiple myeloma treated at our institution.ResultsWe describe 12 patients who experien

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… The CM cases reported here also suggest that patients with prior anthracycline exposure may have increased susceptibility to cardiotoxicity from reactive oxygen species generated from proteasome inhibitor–induced eNOS uncoupling. … Enrico O Gabriele B Nadia C Sara G Daniele V Giulia C Antonio S Mario P Unexpected cardiotoxicity in haematological bortezomib treated patients Br J Haematol 2007 138 3 396 397 10.1111/j.1365-2141.2007.06659.x 17561972 38. …

The combination therapy with venetoclax in therapeutic strategy of acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is characterized by the malignant transformation and proliferation of lymphoid progenitor cells in the bone marrow, blood, and extramedullary sites. Leukemic cells can develop drug resistance both before and after treatment, complicating disease management. Combination therapy with Venetoclax has been shown to enhance the efficacy of standard anti-leukemia drugs. Therefore, this study aims to review combination treatment strategies as potential therapeutic alternatives, drawing on evidence from previous published literature. METHODS: This narrativ

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… nausea, vomiting, diarrhea | [ 18 , 52 – 54 ] Venetoclax + Ponatinib + Dexamethasone | R/R Ph + ALL ( n = 3) | Clinical trial | CR 50%, CMR maintained | Not specified | [ 55 ]– [ 56 ] Venetoclax + Vincristine | R/R ALL | Clinical trial | CR 38–65% for relapsed, 100% newly diagnosed | Hematologic, some cardiotoxicity … Although high doses of Venetoclax have been associated with cardiotoxicity, no unexpected safety issues were observed when used in combination with vincristine. …

The role of cholesterol metabolism in leukemia.

Leukemia is a common hematological malignancy with overall poor prognosis. Novel therapies are needed to improve the outcome of leukemia patients. Cholesterol metabolism reprogramming is a featured alteration in leukemia. Many metabolic-related genes and metabolites are essential to the progress and drug resistance of leukemia. Exploring potential therapeutical targets related to cholesterol homeostasis is a promising area. This review summarized the functions of cholesterol and its derived intermediate metabolites, and also discussed potential agents targeting this metabolic vulnerability in

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… anion channel 1 (VDAC1) signaling pathway. 37 Ubiquinone-based compounds could inhibit human leukemic cell growth by disrupting trans-plasma membrane electron transport (tPMET) and then disturbing intracellular redox homeostasis. 38 Besides, CoQ(10) has protective effects on anthracyclines induced cardiotoxicity … J Med Chem 2013 ; 56 (8) : 3168 – 3176 . 23432053 10.1021/jm301585z [39] Iarussi D Auricchio U Agretto A Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: control study in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma . …

Drug-Drug Interactions of Cannabidiol with Standard-of-Care Chemotherapeutics.

Cannabidiol (CBD) is an easily accessible and affordable Marijuana (Cannabis sativa L.) plant derivative with an extensive history of medical use spanning thousands of years. Interest in the therapeutic potential of CBD has increased in recent years, including its anti-tumour properties in various cancer models. In addition to the direct anticancer effects of CBD, preclinical research on numerous cannabinoids, including CBD, has highlighted their potential use in: (i) attenuating chemotherapy-induced adverse effects and (ii) enhancing the efficacy of some anticancer drugs. Therefore, CBD is ga

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… Its main adverse effects include cardiotoxicity, neurotoxicity, nephrotoxicity, and hepatotoxicity [ 107 ]. … Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity. Pharmacol. Rev. 2004;56:185–229. doi: 10.1124/pr.56.2.6. 107. Carvalho C., Santos R.X., Cardoso S., Correia S., Oliveira P.J., Santos M.S., Moreira P.I. …

Nanotechnology in Prostate Cancer: PSMA-Targeted Nanoplatforms, TME-Responsive Therapy, Immunomodulation, and Clinical Translation Challenges.

The field of nanotechnology has demonstrated considerable potential in the diagnosis and treatment of prostate cancer, particularly through the use of prostate-specific membrane antigen (PSMA)-targeted platforms and tumor microenvironment (TME)-responsive systems. In the context of diagnosis, nanoparticle-based molecular imaging probes have been shown to enhance detection sensitivity and specificity. These probes include superparamagnetic iron oxide, which is utilized in magnetic resonance imaging, and near-infrared fluorescent nanomicelles. Additionally, nanostructured liquid biopsy systems h

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… ; CRPC models; LNCaP/PC-3 xenografts Higher tumor inhibition in PSMA⁺ xenografts; reduced cardiotoxicity vs free drug; IC 5 0 reduced by ~40% in combination therapy [ 78–80 , 126 , 127 ] Polymeric nanoparticle PLGA; PAMAM dendrimer Docetaxel; cabazitaxel; camptothecin PSMA ligand (DUPA, A10 aptamer); … ; CRPC models; LNCaP/PC-3 xenografts | Higher tumor inhibition in PSMA⁺ xenografts; reduced cardiotoxicity vs free drug; IC 5 0 reduced by ~40% in combination therapy | [ 78–80 , 126 , 127 ] Polymeric nanoparticle | PLGA; PAMAM dendrimer | Docetaxel; cabazitaxel; camptothecin | PSMA ligand (DUPA, A10 …

Does DPP-IV Inhibition Offer New Avenues for Therapeutic Intervention in Malignant Disease?

Dipeptidyl peptidase IV (DPP-IV, CD26) is frequently dysregulated in cancer and plays an important role in regulating multiple bioactive peptides with the potential to influence cancer progression and the recruitment of immune cells. Therefore, it represents a potential contributing factor to cancer pathogenesis and an attractive therapeutic target. Specific DPP-IV inhibitors (gliptins) are currently used in patients with type 2 diabetes mellitus to promote insulin secretion by prolonging the activity of the incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypep

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… Another study on rats demonstrated that a 10-day treatment with sitagliptin prior to the administration of doxorubicin ameliorated ECG changes, lowered the level of serum markers of cardiotoxicity, and improved histopathological alterations in the heart. … Similarly, linagliptin treatment ameliorated the cardiotoxicity induced by the repeated administration of lower doses of doxorubicin and reduced lipid peroxidation [ 171 ]. An improved antioxidant status after gliptin administration was also observed in methotrexate-induced hepatic injury [ 173 ]. …

Potential Protective Role Exerted by Secoiridoids from Olea europaea L. in Cancer, Cardiovascular, Neurodegenerative, Aging-Related, and Immunoinflammatory Diseases.

Iridoids, which have beneficial health properties, include a wide group of cyclopentane [c] pyran monoterpenoids present in plants and insects. The cleavage of the cyclopentane ring leads to secoiridoids. Mainly, secoiridoids have shown a variety of pharmacological effects including anti-diabetic, antioxidant, anti-inflammatory, immunosuppressive, neuroprotective, anti-cancer, and anti-obesity, which increase the interest of studying these types of bioactive compounds in depth. Secoiridoids are thoroughly distributed in several families of plants such as Oleaceae, Valerianaceae, Gentianaceae a

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… rats | 100 or 200 mg/Kg | OL modulated the CPK, lactate deshydrogenase, aspartate and alanine aminotransferase, and lipid peroxidation | [ 147 ] Doxorubicin-induced acute cardiotoxicity in rats | 100 or 200 mg/Kg | OL reduced the acetate and succinate levels. … Similarly, OL administrated via intravenous decreased some markers of cardiovascular disease in DOX-induced acute cardiotoxic rats such as creatine phosphokinase (CPK), lactate deshydrogenase, aspartate and alanine aminotransferase, and lipid peroxidation in myocardial tissue [ 147 ]. …

Practical management of disease-related manifestations and drug toxicities in patients with multiple myeloma.

Multiple myeloma (MM) is a very heterogeneous disease with multiple symptoms and clinical manifestations. MM affects mainly elderly patients and is difficult to manage in the presence of comorbidities, polypharmacy, frailty and adverse events of disease-targeted drugs. The rapid changes in MM treatment resulting from constant innovations in this area, together with the introduction of numerous new drugs with distinct mechanisms of action and toxicity profiles, have led to an increased complexity in the therapeutic decision-making and patient management processes. The prolonged exposure to nove

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… There are a small number of studies suggesting that angiotensin-converting enzyme inhibitors such as enalapril, angiotensin receptor blockers such as candesartan, and selected beta-blockers such as carvedilol and nebivolol, may be the preferred agents to reduce the risk of cardiotoxicity, in addition … Cardiotoxicity of chemotherapeutic agents and radiotherapy-related heart disease: ESMO clinical practice guidelines. Ann Oncol Off J Eur Soc Med Oncol (2010) 21(Suppl 5):v277–82. doi: 10.1093/annonc/mdq200 52. Ludwig H, Delforge M, Facon T, Einsele H, Gay F, Moreau P, et al. …

A technical note on emerging combination approach involved in the onconanotherapeutics.

Cancer is the second cause of mortality worldwide, and the currently available conventional treatment approach is associated with serious side effects and poor clinical outcomes. Based on the outcome of the exploratory preclinical and clinical studies, it was found that therapeutic response increases multiple folds when anticancer drugs are used in combination. However, the conventional combination of anticancer drugs was associated with various limitations such as increased cost of treatment, systemic toxicity, drug resistance, and reduced pharmacokinetic attributes. Hence, attempts were made

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… For example, DOX-loaded polyethylene glycol (PEG) or PEGylated liposomes impart reduced cardiotoxicity in comparison to free DOX (O’Brien et al., 2004 ). … Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. …

Covalent targeting of PSMD14 by Eupalinolide B induces oncoprotein degradation and apoptosis in acute promyelocytic leukemia cells.

Treatment of acute promyelocytic leukemia (APL) remains challenged by toxicities associated with current regimens, highlighting the need for novel and safer therapeutic agents. Here, we identify Eupalinolide B (EB), a natural sesquiterpene lactone isolated from Eupatorium lindleyanum DC., as a potent anti-leukemic compound targeting the human APL-derived HL-60 cell line. Through integrated chemoproteomic profiling and functional validation, we demonstrate that EB covalently binds and inhibits 26S proteasome non-ATPase regulatory subunit 14 (PSMD14), a deubiquitinase enzyme (DUB) within the 19S

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… Treatment with ATRA/ATO is associated with significant toxicities, including ATRA syndrome, arsenic-induced neurotoxicity, cardiotoxicity, and the potential risk of secondary malignancies. 3,5,6 Furthermore, the burden of intensive chemotherapy and the need for hematopoietic stem cell transplantation … Discussion Although APL is now considered highly curable with ATRA and ATO–based regimens, treatment is still associated with significant toxicities, including life-threatening coagulopathy, neuro- and cardiotoxicity, and an increased risk of secondary malignancies. 3,5,6 These limitations highlight …

Accelerated Aging in Cancer and Cancer Treatment: Current Status of Biomarkers.

BackgroundAging in humans is a heterogeneous process influenced by both biological and chronological factors. Biological age reflects an individual's physiological reserve and functional status. Increasing evidence suggests that cancer and its therapies accelerate biological aging. Many biomarkers have been evaluated to assess the biological age of patients with cancer. These biomarkers are emerging as potential tools to predict cancer-related toxicity and an individual's functional capacity as well as to individualize treatment.MethodsThis review summarizes the current literature on aging bio

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… Xia et al. demonstrated that continuous doxorubicin therapy resulted in an increased amount of SASP in cardiac muscle cells, often leading to cardiac senescence and therefore, cardiotoxicity [ 74 ]. … Xia W., Chang B., Li L., et al., “MicroRNA Therapy Confers Anti‐Senescent Effects on Doxorubicin‐Related Cardiotoxicity by Intracellular and Paracrine Signaling,” Aging (Albany NY) 13, no. 23 (2021): 25256–25270. 75. Mandelblatt J. S., Small B. …

Research progress of novel anti-tumor drug formulations.

Cancers have become the second leading cause of death worldwide, following cardiovascular diseases.Traditional anti- cancer strategies, including radiotherapy chemotherapy, surgery, and targeted therapies, have been widely used but are often reassessed due to their significant side effects and relatively low cure rate. Recently, the development of novel formulations for anti-tumor drugs has gained considerable attention, marking a pivotal step forward in cancer treatment advancements. These innovative formulations aim to enhance the therapeutic efficacy of anti-tumor drugs by employing advance

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… They also cause cardiotoxicity, fertility and sexual toxicity. Most importantly, these long-term side effects can last for many years, with lasting effects on a patient’s quality of life. … Nanomedicine | Type | Therapeutic Use | Comments Doxil | Liposome | Cancer (ovarian, multiple myeloma, etc.) | First approved liposomal drug; reduces cardiotoxicity Abraxane | Nanoparticle-bound albumin | Breast, pancreatic, NSCLC | Enhanced solubility of paclitaxel, higher tumor uptake Onivyde | Liposome …