Class Of Chemotherapeutic Agents Research Articles

Recent Advances in Structural Optimization of Quinazoline-Based Protein Kinase Inhibitors for Cancer Therapy (2021-Present).

Cancer is a complicated, multifaceted disease that can impact any organ in the body. Various chemotherapeutic agents have a low selectivity and are very toxic when used alone or in combination with others. Resistance is one of the most important hurdles that develop due to the use of many anticancer therapeutics. As a result, treating cancer requires a target-specific palliative care strategy. Remarkable scientific discoveries have shed light on several of the molecular mechanisms underlying cancer, resulting in the development of various targeted anticancer agents. One of the most important heterocyclic motifs is quinazoline, which has a wide range of biological uses and chemical reactivities. Newer, more sophisticated medications with quinazoline structures have been found in the last few years, and great strides have been made in creating effective protocols for building these pharmacologically active scaffolds. A new class of chemotherapeutic agents known as quinazoline-based derivatives possessing anticancer properties consists of several well-known compounds that block different protein kinases and other molecular targets. This review highlights recent updates (2021-2024) on various quinazoline-based derivatives acting against different protein kinases as anticancer chemotherapeutics. It also provides guidance for the design and synthesis of novel quinazoline analogues that could serve as lead compounds.

Design, Synthesis, and Antitumor Evaluation of an Opioid Growth Factor Bioconjugate Targeting Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) presents a formidable challenge with high lethality and limited effective drug treatments. Its heightened metastatic potential further complicates the prognosis. Owing to the significant toxicity of current chemotherapeutics, compounds like [Met5]-enkephalin, known as opioid growth factor (OGF), have emerged in oncology clinical trials. OGF, an endogenous peptide interacting with the OGF receptor (OGFr), plays a crucial role in inhibiting cell proliferation across various cancer types. This in vitro study explores the potential anticancer efficacy of a newly synthesized OGF bioconjugate in synergy with the classic chemotherapeutic agent, gemcitabine (OGF-Gem). The study delves into assessing the impact of the OGF-Gem conjugate on cell proliferation inhibition, cell cycle regulation, the induction of cellular senescence, and apoptosis. Furthermore, the antimetastatic potential of the OGF-Gem conjugate was demonstrated through evaluations using blood platelets and AsPC-1 cells with a light aggregometer. In summary, this article demonstrates the cytotoxic impact of the innovative OGF-Gem conjugate on pancreatic cancer cells in both 2D and 3D models. We highlight the potential of both the OGF-Gem conjugate and OGF alone in effectively inhibiting the ex vivo pancreatic tumor cell-induced platelet aggregation (TCIPA) process, a phenomenon not observed with Gem alone. Furthermore, the confirmed hemocompatibility of OGF-Gem with platelets reinforces its promising potential. We anticipate that this conjugation strategy will open avenues for the development of potent anticancer agents.

Treatment modalities favoring outcome in well-differentiated neuroendocrine tumors G3.

Neuroendocrine neoplasms (NEN) are a rare and heterogenous group of tumors arising from neuroendocrine cells in multiple organs. Neuroendocrine tumors (NET) G3 encompass a small subgroup accounting for less than 10% of all neuroendocrine neoplasms. In contrast to NET G1 and G2 as well as neuroendocrine carcinomas (NEC), in NET G3 data on treatment and patient outcomes are still limited. Especially in a metastasized tumor stage, the role of surgery, peptide receptor radionucleotide therapy (PRRT), and systemic chemotherapy is not clearly defined. In this real-life cohort, we consecutively analyzed clinical outcome in NET G3 patients receiving different diagnostic and treatment. We found that even metastasized NET G3 patients undergoing surgery, or receiving radiation, somatostatin analogues (SSA), and PRRT showed a clear survival benefit. Interestingly, all treatment regimen were superior to classical chemotherapeutic agents. In addition, somatostatin receptor (SSTR) PET-CT, FDG PET-CT, and repetitive biopsies were shown to be useful diagnostic and prognostic tools in NET G3. Our study demonstrates that patients with highly proliferative NET G3 might benefit from less aggressive treatment modalities commonly used in low proliferative NEN.

Natural small-molecules reverse Xeroderma Pigmentosum Complementation Group C (XPC) deficient-mediated drug-resistance in renal cell carcinoma

BackgroundRenal cancer is insensitive to radiotherapy or most chemotherapies. While the loss of the XPC gene was correlated with drug resistance in colon cancer, the expression of XPC and its role in the drug resistance of renal cancer have not yet been elucidated. With the fact that natural small-molecules have been adopted in combinational therapy with classical chemotherapeutic agents to increase the drug sensitivity and reduce adverse effects, the use of herbal compounds to tackle drug-resistance in renal cancer is advocated. PurposeTo correlate the role of XPC gene deficiency to drug-resistance in renal cancer, and to identify natural small-molecules that can reverse drug-resistance in renal cancer via up-regulation of XPC. MethodsIHC was adopted to analyze the XPC expression in human tumor and adjacent tissues. Clinical data extracted from The Cancer Genome Atlas (TCGA) database were further analysed to determine the relationship between XPC gene expression and tumor staging of renal cancer. Two types of XPC-KD renal cancer cell models were established to investigate the drug-resistant phenotype and screen XPC gene enhancers from 134 natural small-molecules derived from herbal plants. Furthermore, the identified XPC enhancers were verified in single or in combination with FDA-approved chemotherapy drugs for reversing drug-resistance in renal cancer using MTT cytotoxicity assay. Drug resistance gene profiling, ROS detection assay, immunocytochemistry and cell live-dead imaging assay were adopted to characterize the XPC-related drug resistant mechanism. ResultsXPC gene expression was significantly reduced in renal cancer tissue compared with its adjacent tissue. Clinical analysis of TCGA database also identified the downregulated level of XPC gene in renal tumor tissue of stage IV patients with cancer metastasis, which was also correlated with their lower survival rate. 6 natural small-molecules derived from herbal plants including tectorigenin, pinostilbene, d-pinitol, polygalasaponin F, atractylenolide III and astragaloside II significantly enhanced XPC expression in two renal cancer cell types. Combinational treatment of the identified natural compound with the treatment of FDA-approved drug, further confirmed the up-regulation of XPC gene expression can sensitize the two types of XPC-KD drug-resistant renal cancer cells towards the FDA-approved drugs. Mechanistic study confirmed that GSTP1/ROS axis was activated in drug resistant XPC-KD renal cancer cells. ConclusionXPC gene deficiency was identified in patient renal tumor samples, and knockdown of the XPC gene was correlated with a drug-resistant phenotype in renal cancer cells via activation of the GSTP1/ROS axis. The 6 identified natural small molecules were confirmed to have drug sensitizing effects via upregulation of the XPC gene. Therefore, the identified active natural small molecules may work as an adjuvant therapy for circumventing the drug-resistant phenotype in renal cancer via enhancement of XPC expression.

Susceptibility of periodontal pathogens to a novel target-specific drug delivery system containing self-nanoemulsifying curcumin: An in vitro study.

Long-term use of many classic chemotherapeutic agents as adjuncts in the management of periodontitis has adverse complications, leading to seeking out naturopathic remedies. Although curcumin has been investigated in managing periodontitis, its therapeutic benefits have not been fully explored due to its limited solubility in an aqueous medium. This study aimed to develop a novel target-specific drug delivery system containing 1% self-nanoemulsifying curcumin (SNEC) in a hydroxypropylmethylcellulose (HPMC) matrix and evaluate the susceptibility of periodontal pathogens to this system in vitro. Its antibacterial activity against Tannerella forsythia, Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans was evaluated and compared to pure nano-curcumin and SNEC alone by estimating their minimum inhibitory concentrations (MIC). The antibacterial activity of pure nano-curcumin, SNEC, and SNEC in HPMC against the four periodontal pathogens evaluated in terms of MIC was recorded in the range of 0.2‒0.4, 0.4‒0.8, and 0.2‒0.8 µg/mL, respectively. However, the MIC of all three curcumin formulations against the periodontal pathogens tested was higher than that of the standard moxifloxacin. While both pure nano-curcumin and SNEC showed increasing values of inhibition zones with increasing concentrations on disk diffusion assay, lower concentrations of SNEC in HPMC did not show a zone of inhibition against the tested pathogens. The novel delivery system containing SNEC in HPMC may be a potential adjunct in managing periodontitis due to its probable sustained antimicrobial activity against the tested periodontal pathogens.

Co-delivering irinotecan and imiquimod by pH-responsive micelle amplifies anti-tumor immunity against colorectal cancer

Irinotecan (IRT), a classic clinical chemotherapeutic agent for treating colorectal cancer, has been found to induce immunogenic cell death (ICD) while exerting cytotoxicity in tumor cells. This effect is likely to be amplified in combination with immune modulators. Unfortunately, free drugs without targeting capacity would receive poor outcomes and strong side effects. To address these issues, in this work, an acid-sensitive micelle based on an amphiphilic poly(β-amino ester) derivative was constructed to co-deliver IRT and the immune adjuvant imiquimod (IMQ), termed PII. PII kept stable under normal physiological conditions. After internalization by tumor cells, PII dissociated in acidic lysosomes and released IRT and IMQ rapidly. In the CT26 tumor mouse model, PII increased the intra-tumoral SN38 (the active metabolite of IRT) and IMQ concentrations by up to 9.39 and 3.44 times compared with the free drug solution. The tumor inhibition rate of PII achieved 87.29%. This might profit from that IRT induced ICD, which promoted dendritic cells (DCs) maturation and intra-tumoral infiltration of CD8+ T cells. In addition, IMQ enhanced the antigen presenting ability of DCs and stimulated tumor associated macrophages to secrete tumor-killing cytokines. PII provided an effective strategy to combat colorectal cancer by synergy of chemotherapy and immunoregulation.

Time-Tested Strategies in Modern Context: A Bibliometric Study of Chemotherapy's Continued Importance in Colorectal Cancer Treatment.

In the landscape of colorectal cancer treatment, classical chemotherapeutic agents such as 5-fluorouracil, capecitabine, irinotecan, oxaliplatin, trifluridine, and tipiracil have historically played a pivotal role. This study presents a comprehensive bibliometric analysis of the top 100 most influential articles focusing on these classic chemotherapy drugs in the management of colorectal cancer. With this, we shed light on their current importance, despite the emergence of new therapeutic targets and treatments in the field of oncology. Systematically evaluating research outputs, this analysis reveals a prevalence of co-authorship among institutions, countries (led by the United States, China, and Europe), and researchers highlighting the global and collaborative nature of efforts in research, utilization, and development of these drugs. Three thematic axes lead the research: pharmacogenetics, the development of new pharmaceutical forms, and the use of adjuvants. This research serves as a foundation for future endeavors, aiding researchers, clinicians, and policymakers in making informed decisions about the direction of research and development in the dynamic field of colorectal cancer therapy.

Cardiotoxicity of breast cancer chemotherapy.

Breast cancer is one of the leading causes of malignancy affecting women in the United States. Although many effective treatments are available, most come with notable side effects that providers and patients must take into consideration. Various classes of chemotherapeutic agents, including anthracyclines and human epidermal growth factor receptor-2 antagonists, are known to be toxic to myocardial tissue. In this review article, we discuss what is reported in the literature regarding the cardiotoxicity of these agents as well as how to monitor and prevent cardiac injury and dysfunction.

A novel camptothecin derivative, ZBH-01, exhibits superior antitumor efficacy than irinotecan by regulating the cell cycle

BackgroundIrinotecan (CPT-11) is a classic chemotherapeutic agent that plays an important role in the clinical treatment of metastatic colon cancer and other malignant tumors. We previously designed a series of novel irinotecan derivatives. In this study, we select one representative, ZBH-01, to investigate its sophisticated antitumor mechanism in colon tumor cells.MethodsThe cytotoxic activity of ZBH-01 on colon cancer cells was evaluate by MTT or Cell Counting Kit-8 (CCK8) assay, 3D and xenograft model. The inhibitory effect of ZBH-01 on TOP1 was detected by DNA relaxation assay and Immuno Complex of Ezyme (ICE) bioassay. The molecular mechanism of ZBH-01 was explored by Next-Generation Sequencing (NGS), bioinformatics analyses, flow cytometry, qRT-PCR, and western blot etc.ResultsZBH-01 can induce obvious DNA damage and has superior antitumor activity against colon cancer cells compared to CPT-11 and SN38 (7-Ethyl-10-hydroxy camptothecin, the in vivo active form of CPT-11) both in vivo and in vitro. Its inhibitory effect on topoisomerase I (TOP1) was also comparable with these two control drugs. There are a much larger number of 842 downregulated and 927 upregulated mRNAs in ZBH-01 treatment group than that in the controls. The most significantly enriched KEGG pathways for these dysregulated mRNAs were DNA replication, the p53 signaling pathway, and the cell cycle. After constructing a protein–protein interaction (PPI) network and screening out a prominent cluster, 14 involved in the cell cycle process was identified. Consistently, ZBH-01 induced G0/G1 phase arrest in colon cancer cells, while CPT-11/SN38 caused S phase arrest. The initiation of apoptosis by ZBH-01 was also superior to CPT-11/SN38, followed by the increased expression of Bax, active caspase 3, and cleaved-PARP, and decreased expression of Bcl-2. Additionally, CCNA2 (cyclin A2), CDK2 (cyclin-dependent kinase 2), and MYBL2 (MYB proto-oncogene like 2) might be involved in the G0/G1 cell cycle arrest induced by ZBH-01.ConclusionsZBH-01 can be an antitumor candidate drug for preclinical study in the future.

Cardiac Molecular Remodeling by Anticancer Drugs: Doxorubicin Affects More Metabolism While Mitoxantrone Impacts More Autophagy in Adult CD-1 Male Mice

Doxorubicin (DOX) and mitoxantrone (MTX) are classical chemotherapeutic agents used in cancer that induce similar clinical cardiotoxic effects, although it is not clear if they share similar underlying molecular mechanisms. We aimed to assess the effects of DOX and MTX on the cardiac remodeling, focusing mainly on metabolism and autophagy. Adult male CD-1 mice received pharmacologically relevant cumulative doses of DOX (18 mg/kg) and MTX (6 mg/kg). Both DOX and MTX disturbed cardiac metabolism, decreasing glycolysis, and increasing the dependency on fatty acids (FA) oxidation, namely, through decreased AMP-activated protein kinase (AMPK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) content and decreased free carnitine (C0) and increased acetylcarnitine (C2) concentration. Additionally, DOX heavily influenced glycolysis, oxidative metabolism, and amino acids turnover by exclusively decreasing phosphofructokinase (PFKM) and electron transfer flavoprotein-ubiquinone oxidoreductase (ETFDH) content, and the concentration of several amino acids. Conversely, both drugs downregulated autophagy given by the decreased content of autophagy protein 5 (ATG5) and microtubule-associated protein light chain 3 (LC3B), with MTX having also an impact on Beclin1. These results emphasize that DOX and MTX modulate cardiac remodeling differently, despite their clinical similarities, which is of paramount importance for future treatments.

P381 TEAMWORK IS SUCCESSFULL (4): PROGRESSION OF CORONARY ATHEROSCLEROSIS IN A PERIPHERAL T–CELL LYMPHOMA AND PAPILLARY RENAL CELL CARCINOMA SURVIVOR

Abstract Introduction Growing evidence highlight cancer and cardiovascular diseases (CVD) share common risk factors, including genetic ones, and underlying pathogenesis. Such paradigm has significant implications for cancer survivors, an exponential growing cohort of patients (Pts), due to notable improvements in survival achieved with new oncological treatments. However, many new agents of targeted– and immuno–therapy can cause cardiac damage, mainly for vascular involvement, a pathophysiological mechanism different from classic chemotherapeutic agents. We present the case of left ventricular systolic dysfunction (LVSD) in a man with metastatic papillary renal cell carcinoma (PRCC) previously exposed to anthracyclines for former peripheral T–cell lymphoma (PTCL). He came to our attention for cardiological assessment before starting immunotherapy (Nivolumab), due to the failure of Tyrosine kinase inhibitor (TKIs) (Pazopanib) treatment. Clinical case A 74–year–old Pt with hypertension, severe renal dysfunction, dyslipidemia, and exertional dyspnea (NYHA II) presented at transthoracic echocardiogram (TTE) a normal size chambers with mild concentric hypertrophy and a clinically stable moderate LVSD (LVEF 35–40%) at periodic evaluation. Pt was also performing his radiological follow–up for the estimation of metastases with CT, twice a year since 2016. A retrospective review of these non–contrast and non–ECG–gated CT highlighted an extensive increase in coronary artery calcifications during the last four years, started with the beginning of TKIs therapy. In 2018 only mild LAD calcification was detectable (Figure 1), while in 2022 a severe three–vessel coronary atherosclerosis was present (Figure 3). After multi–disciplinary discussion, an aggressive correction of multiple cardiovascular risk factors (starting Rosuvastatin and adjusting Bisoprolol) was performed and immunotherapy started without any adverse event. Conclusions Non–ECG–gated CT routinely performed for monitoring the state of the oncological disease is a useful tool for the evaluation of coronary artery calcific burden and accelerated atherosclerosis. It provides additional information beyond the traditional evaluation of CV risk and must be integrated with clinical and laboratory data.

Statins to Prevent Anthracyclines-Induced Cardiotoxicity

While anthracyclines are a class of chemotherapeutic agents that have improved the treatment of a broad spectrum of malignancies, it is one of the most cardiotoxic agents used to treat the tumor. Despite their dose-dependent cardiotoxicity, anthracyclines-based chemotherapy has become the main stay of tumor therapy due to its efficacy. Meanwhile, Statins, widely used in the clinical setting to reduce serum cholesterol levels and to reduce cardiac morbidity and mortality, have pleiotropic biological effects independent of their lipid-lowering effects. Many studies at home and abroad believe that statins can prevent the cardiotoxicity caused by anthracyclines and propose that statins can play beneficial pleiotropic cardiovascular effects through anti-inflammatory and antioxidant mechanisms, thus playing a cardioprotective effect. Illuminating the mechanisms of Anthracyclines-induced cardiotoxicity and Statins associated therapeutic continue to be the main focus in the field of anti-tumor. Therefore, we summarized the current research surrounding the mechanisms of anthracyclines-induced cardiotoxicity and the protective effect of statins on anthracyclines-induced cardiotoxicity and its possible mechanism.

Theranostics for oncological therapy: results from worldwide research and the paths of development

Theranostics is a field of medicine with the aim to establish tools for a specific targeted therapy based on early diagnosis of diseases. This effect is primarily due to targeted delivery of the therapeutic agent to the target cells. The development of a clinically effective theranostic drug will be the greatest medical breakthrough. This paper presents an analytical mini-review of some modern approaches to find a solution to the core of the problems of theranostics for oncological therapy and discusses recent studies on the use of radiopharmaceuticals, that can be diagnostic and therapeutic, and systems for visualization of radiopharmaceuticals by means of magnetic resonance imaging for therapy of cancerous tumors. Information is given on application of various systems using fluorescent agents such as anti-Stokes fluorophores, the signal from which is well observed, compared to other fluorescent substances, on a background of the reflected irradiance from tissues surrounding cancer cells. This paper also presents details on the comparative use of classical chemotherapeutic agents and promising drugs developed on the basis of natural substances, for example, sulforaphane and cytochrome c, that have lower toxicity.

Flavin-Conjugated Pt(IV) Anticancer Agents

In situ activation of Pt(IV) to Pt(II) species is a promising strategy to control the anticancer activity and overcome the off-target toxicity linked to classic platinum chemotherapeutic agents. Herein, we present the design and synthesis of two new asymmetric Pt(IV) derivatives of cisplatin and oxaliplatin (1·TARF and 2·TARF, respectively) bearing a covalently bonded 2',3',4',5'-tetraacetylriboflavin moiety (TARF). 1H and 195Pt NMR spectroscopy shows that 1·TARF and 2·TARF can be effectively activated into toxic Pt(II) species, when incubated with nicotinamide adenine dinucleotide, sodium ascorbate, and glutathione in the dark and under light irradiation. Density functional theory studies of the dark Pt(IV)-to-Pt(II) conversion of 2·TARF indicate that the process involves first hydride transfer from the donor to the flavin moiety of the complex, followed by electron transfer to the Pt(IV) center. When administered to MDA-MB-231 breast cancer cells preincubated with nontoxic amounts of ascorbate, 2·TARF displays enhanced toxicity (between 1 and 2 orders of magnitude), suggesting that the generation of oxaliplatin can selectively be triggered by redox activation. Such an effect is not observed when 2 and TARF are coadministered under the same conditions, demonstrating that covalent binding of the flavin to the Pt complex is pivotal.

Targeted siRNA lipid nanoparticles for the treatment of KRAS-mutant tumors

K-RAS is a highly relevant oncogene that is mutated in approximately 90% of pancreatic cancers and 20–25% of lung adenocarcinomas. The aim of this work was to develop a new anti-KRAS siRNA therapeutic strategy through the engineering of functionalized lipid nanoparticles (LNPs). To do this, first, a potent pan anti-KRAS siRNA sequence was chosen from the literature and different chemical modifications of siRNA were tested for their transfection efficacy (KRAS knockdown) and anti-proliferative effects on various cancer cell lines. Second, a selected siRNA candidate was loaded into tLyp-1 targeted and non-targeted lipid nanoparticles (LNPs). The biodistribution and antitumoral efficacy of selected siRNA-loaded LNP-prototypes were evaluated in vivo using a pancreatic cancer murine model (subcutaneous xenograft CFPAC-1 tumors). Our results show that tLyp-1-tagged targeted LNPs have an enhanced accumulation in the tumor compared to non-targeted LNPs. Moreover, a significant reduction in the pancreatic tumor growth was observed when the anti-KRAS siRNA treatment was combined with a classical chemotherapeutic agent, gemcitabine. In conclusion, our work demonstrates the benefits of using a targeting approach to improve tumor accumulation of siRNA-LNPs and its positive impact on tumor reduction.

New targeted therapies for non-small cell lung cancer

Background: Lung cancer is representative of a high frequency and high mortality disease and ranks at the top in incidence and mortality in Korea, when excluding thyroid cancer. In this manuscript, we focused on current targeted therapies for lung cancer used widely in the medical field.Current Concepts: The majority of patients with lung cancer cannot be treated with surgery only and require chemotherapeutics or radiation therapy. Currently, classical chemotherapeutic agents, targeted agents, and immune checkpoint inhibitors are the most widely used. Recently, the Research and Development of antibody-drug conjugates is gaining attention, and this may become a more widely prescribed treatment in the future. Among the available treatment options, targeted therapy is becoming increasingly feasible and widespread for treating inoperable lung cancers, where driver mutations have been identified, and for adjuvant or neoadjuvant therapies. Next-generation sequencing (NGS) improves the ability to identify driver mutations that were previously difficult to detect and can also be performed on blood samples where no cancer tissue is available for testing. This makes it possible to identify therapeutic targets for targeted therapy more rapidly.Discussion and Conclusion: The most common type of lung cancer in Korea is adenocarcinoma, for which a driver mutation has been identified. Newly developed drugs target previously problematic mutations or cancer cell lines that have acquired resistance induced during the treatment process. The survival rate of patients with lung cancer is expected to improve with the development of tailored treatments for targets identified from the NGS data of the patient. This paper will help clinicians understand the current state of targeted therapies for lung cancer treatment.

Integrated radiochemotherapy study of ZIF-8 coated with osteosarcoma-platelet hybrid membranes for the delivery of Dbait and Adriamycin.

Introduction: The toxic side effects of systemic high-dose chemotherapy and poor sensitivity to radiotherapy hinder the survival rate of patients with osteosarcoma (OS). Nanotechnology offers new solutions for OS treatment; however, conventional nanocarriers suffer from inadequate targeting of tumors and short in vivo circulation time. Methods: Here, we designed a novel drug delivery system, [Dbait-ADM@ZIF-8]OPM, which uses OS-platelet hybrid membranes to encapsulate nanocarriers, to enhance the targeting and circulation time of nanocarriers, thereby enabling high enrichment of the nanocarriers in OS sites. Results: In the tumor microenvironment, the pH-sensitive nanocarrier, which is the metal-organic framework ZIF-8, dissociates to release radiosensitizer Dbait and the classical chemotherapeutic agent Adriamycin for the integrated treatment of OS via radiotherapy and chemotherapy. Benefiting from the excellent targeting ability of the hybrid membrane and the outstanding drug loading capacity of the nanocarrier, [Dbait-ADM@ZIF-8]OPM showed potent anti-tumor effects in tumor-bearing mice with almost no significant biotoxicity. Conclusion: Overall, this project is a successful exploration of the combination of radiotherapy and chemotherapy of OS treatment. Our findings solve the problems of the insensitivity of OS to radiotherapy and the toxic side effects of chemotherapy. Furthermore, this study is an expansion of the research of OS nanocarriers and provides new potential treatments for OS.

Narrative Review of Drug-Associated Nail Toxicities in Oncologic Patients.

Nail toxicity represents one of the most common cutaneous adverse effects of both classic chemotherapeutic agents and new oncologic drugs, including targeted treatments and immunotherapy. We aimed to provide a comprehensive literature review of nail toxicities derived from conventional chemotherapeutic agents, targeted therapies (EGFR inhibitors, multikinase inhibitors, BRAF and MEK inhibitors) and immune checkpoint inhibitors (ICIs), including clinical presentation, implicated drugs and approaches for prevention and management. Retrieved literature from PubMed registry database was reviewed to include all articles published up to May 2021 relevant to the clinical presentation, diagnosis, incidence, prevention, and treatment of oncologic treatment-induced nail toxicity. The internet was searched for relevant studies. A wide spectrum of nail toxicities is associated with both, conventional and newer anticancer agents. The frequency of nail involvement, especially with immunotherapy and new targeted agents remains unknown and patients with different cancer types receiving different regimens may develop the same nail disorder, whereas patients with the same type of cancer under the same chemotherapeutic treatment may develop different types of nail alterations. The underlying mechanisms of the varying individual susceptibility and the diverse nail responses to various anticancer treatments need further investigation. Early recognition and treatment of nail toxicities can minimize their impact, allowing better adherence to conventional and newer oncologic treatments. Dermatologists, oncologists and other implicated physicians should be aware of these burdensome adverse effects in order to guide management and prevent impairment of patients' quality of life.

Asymptomatic Ventricular Dysfunction and HFrEF Secondary to Classic Chemotherapy

Introduction Advances in oncology, such as better access to the health care system, earlier cancer diagnosis, and new chemotherapies, have led to longer survival of patients with cancer over the last decades. However, this population is vulnerable to drug-related adverse cardiovascular events, like cardiomyopathy, which leads to heart failure and impairs survival and quality of life., Among different classes of chemotherapeutic agents, classically anthracyclines and trastuzumab stand out as the most related to cardiomyopathy. Anthracyclines may cause cardiac dysfunction in [...]

Cancer, cancer treatment and aneurysmatic ascending aorta growth within a retrospective single center study.

Background: Multi-morbidity poses a substantial challenge for health care in an aging population. Recent studies did not provide evidence for general side effects of anti-cancer therapy regarding the growth rate of coincident abdominal aortic aneurysms, although it was suggested that specific therapeutic substances might accelerate growth. Aneurysm pathology, however, differs with respect to localization. Hence, we present the first ever analysis on the association of cancer and cancer therapy with growth alteration of aneurysms of the ascending aorta (AscAA). Patients and methods: A retrospective single-center identification of AscAA+cancer patients was performed in the institutional picture archiving and communication system (PACS). Included were all patients with ≥2 CT angiograms over ≥6 months and additional malignancy. Clinical data and aneurysm diameters were retrieved and analyzed for an association of cancer (stratified by tumor entity) or cancer therapy (stratified by several classes of chemotherapeutic agents and radiation therapy) with annual growth rate, respectively. Statistics included t-test, Wilcoxon test, and a linear regression model accounting for initial AscAA diameter and type of treatment. Results: From 2003 to 2021, 151 patients (median age 70 years; 85% male) with AscAA and coincident 163 malignancies were identified. Prostate (37%) and hematologic cancer (17%) were most frequent. One-hundred-eleven patients (74%) received chemotherapy and 75 patients (50%) had radiation. After exclusion of six patients with an initial AscAA diameter >55 mm, the average annual AscAA growth rate was 0.18±0.64 mm/year, with only 12 patients experiencing a growth rate >1mm/year. Neither tumor entity nor radiation or chemotherapy - alone or in combination - were significantly associated with an alteration of the annual AscAA growth rate. Likewise, a subanalysis for singular chemotherapeutic agents did not reveal a specific association with AscAA growth alteration. Conclusions: Growth rates of AscAA are low in this cohort with coincident malignancy. Cancer and/or chemotherapy or radiation are not associated with an alteration of the annual growth rate. Additional control examinations seem unnecessary.