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Medical Machiavellianism: the tradeoff between benefit and harm with targeted chemotherapy.

Machiavellianism is a word synonymous with the phrase "the end justifies the means", and in this article we have coined the term Medical Machiavellianism to describe the 'cruel-to-be-kind' administration of toxic chemotherapeutic agents in apparent violation of the precept first do no harm, while acknowledging the 'dirty hands' dilemma of having to decide between and choose the lesser of two evils in the setting of advanced cancer--i.e. to treat or not to treat. The perception that 'targeted' therapies are relatively non-toxic and therefore respect the Hippocratic First Commandment by virtue o

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… The analogy of Ehrlich's magic bullet applies to targeted therapies but only in the sense of a ricocheting bullet simultaneously hitting multiple targets. The term targeted therapy also implies, incorrectly, that conventional chemotherapy is untargeted. …

Advancing Cancer-Targeted Nanotherapies with Tumor Homing Peptides.

The development of smart nanoparticles for precision medicine in anticancer drug delivery and controlled release has the potential to revolutionize cancer treatment. This progress is driven by expanding body of preclinical and early clinical studies on anticancer nanoparticles. Despite these advancements, a critical challenge remains achieving a selective and efficient tumor accumulation, along with effective extravasation and deep tissue penetration of nanoparticles into the tumor parenchyma. Affinity targeting strategies using ligands such as homing peptides and antibodies leverage molecular

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… precise effectiveness for the treatment of solid tumors, their mass reduction and inhibition of tumor growing. , Drug Delivery Nanosystems: The Revolution of Controlled Release Paul Ehrlich postulated that an ideal therapeutic agent would be one capable of selectivity reaching its target, taking to a “magic … payloads encapsulated in nanoparticles have already been approved in their free forms, the clinical outcomes of nanoparticle-based formulations have yet to show a significant improvement in overall survival. , The promise of localized concentration and reduced systemic exposure provided by these “magic …

Recent Advances in Cancer Vaccines: Challenges, Achievements, and Futuristic Prospects.

Cancer is a chronic disease, and it can be lethal due to limited therapeutic options. The conventional treatment options for cancer have numerous challenges, such as a low blood circulation time as well as poor solubility of anticancer drugs. Therapeutic cancer vaccines emerged to try to improve anticancer drugs' efficiency and to deliver them to the target site. Cancer vaccines are considered a viable therapeutic technique for most solid tumors. Vaccines boost antitumor immunity by delivering tumor antigens, nucleic acids, entire cells, and peptides. Cancer vaccines are designed to induce lon

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… Building Better Magic Bullets—Improving Unconjugated Monoclonal Antibody Therapy for Cancer. Nat. Rev. Cancer. 2007;7:701–706. doi: 10.1038/nrc2209. 20. Strebhardt K., Ullrich A. Paul Ehrlich’s Magic Bullet Concept: 100 Years of Progress. Nat. Rev. …

Antibody-drug conjugates in urinary tumors: clinical application, challenge, and perspectives.

Urinary tumors primarily consist of kidney, urothelial, and prostate malignancies, which pose significant treatment challenges, particularly in advanced stages. Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic approach, combining monoclonal antibody specificity with cytotoxic chemotherapeutic payloads. This review highlights recent advancements, opportunities, and challenges in ADC application for urinary tumors. We discuss the FDA-approved ADCs and other novel ADCs under investigation, emphasizing their potential to improve patient outcomes. Furthermore, we explore stra

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… About antibody-drug conjugates (ADCs) Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that have their origins in Paul Ehrlich’s vision of “magic bullets” in 1913 ( 16 ). … Paul Ehrlich's magic bullet concept: 100 years of progress . Nat Rev Cancer ( 2008 ) 8 ( 6 ): 473–80 . doi: 10.1038/nrc2394 18469827 17 Ford CH Newman CE Johnson JR Woodhouse CS Reeder TA Rowland GF . …

Antibody-Drug Conjugates and Peptide-Drug Conjugates: Current Understandings and Future Perspectives.

Antibody-drug conjugates (ADCs) and peptide-drug conjugates (PDCs) are modular targeted therapeutics in which molecular recognition is coupled with controlled payload delivery. Owing to their high specificity and precision, they have been regarded as a transformative paradigm for cancer therapy. In this review, current understandings and future perspectives of ADCs and PDCs are synthesized across rational design principles, historical evolution, clinical translation, and emerging formats, aiming to improve practical comprehension and application in oncology. Key determinants of performance: ta

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… The intellectual roots of ADCs trace back to Paul Ehrlich's “magic bullet” concept, but clinical translation required concurrent breakthroughs in antibody engineering, linker design, and payload discovery [ 16 ]. … Emergence of Concepts and Formation of Technology (Early 20th Century – 1990s) The Proposal and Initial Implementation of the “Magic Bullet” Paul Ehrlich, as the father of chemotherapy, first proposed the concept of “magic bullets” in the early 20th century. …

Targeted toxins in brain tumor therapy.

Targeted toxins, also known as immunotoxins or cytotoxins, are recombinant molecules that specifically bind to cell surface receptors that are overexpressed in cancer and the toxin component kills the cell. These recombinant proteins consist of a specific antibody or ligand coupled to a protein toxin. The targeted toxins bind to a surface antigen or receptor overexpressed in tumors, such as the epidermal growth factor receptor or interleukin-13 receptor. The toxin part of the molecule in all clinically used toxins is modified from bacterial or plant toxins, fused to an antibody or carrier liga

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… Introduction In 1906, Paul Ehrlich introduced the concept of targeting cancer cells with a “magic bullet”. His magic bullet consisted of using tissue-specific carriers to deliver toxic agents to neoplastic tissues [ 1 , 2 ]. …

Novel immunotherapeutic strategies of gastric cancer treatment.

Gastric cancer (GC) is the fourth most common cancer and the second most frequent cause of cancer-related deaths, accounting for 10.4% of cancer deaths worldwide. Despite the improvements, estimated cure rates for patients with advanced stages remain poor, and in the metastatic setting, chemotherapy is the mainstay of palliative therapy and results in objective response rates (ORRs) of only 20-40% and median overall survivals (OS) of 8-10 months. Therefore, many investigators believe that the potential for making significant progress lies in understanding and exploiting the molecular biology o

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… chemotherapy observed in the original MAGIC trial [ 3 ]. 4. … MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. New England Journal of Medicine. 2006;355:11–20. doi: 10.1056/NEJMoa055531. 4. Tepper J, Krasna MJ, Niedzwiecki D, et al. …

Erratum: Noninvasive and Invasive Renal Hypoxia Monitoring in a Porcine Model of Hemorrhagic Shock.

An erratum was issued for: Noninvasive and Invasive Renal Hypoxia Monitoring in a Porcine Model of Hemorrhagic Shock. The Protocol section w … mperature probe, 400 series thermistor Novamed 10-1610-040 Part of noninvasive PuO2 monitor Hemmtop Magic Arm 11 inch Amazon B08JTZRKYN Holding invasive oxygen sensor in place HotDog veterinary warming system HotDog V106 For controlling subject temperature during experiment Invasive tissue oxygen measurement device Presens Oxy-1 ST  Compact oxygen trans …

Precision Medicine Through Network Language: Integrating Clinical Insight and Data Expertise.

Precision medicine is facing a critical transition driven by the growing complexity of biological data and the insufficient ability of current models to translate such data into clinically meaningful information. Linear, single-gene approaches are no longer adequate to explain the multifactorial nature of most modern diseases, whose phenotypes emerge from combinations of genetic, molecular, and environmental factors. Network-based precision medicine addresses this by providing a systemic framework capable of integrating heterogeneous omics data, interactomes, and clinical information to identi

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… The failure of traditional reductionism—exemplified by the transition from the “magic bullet” theory to the recognition of multifactorial diseases—demonstrates that knowing the genetic alphabet is not equivalent to understanding the biological narrative. … While the traditional approach seeks a “magic bullet” to hit a single gene, MTBs adopt a systemic view, recognizing that tumor robustness often lies in the functional redundancy of the network, making it necessary to hit multiple critical nodes simultaneously [ 46 ]. …

Mechanistic considerations for the use of monoclonal antibodies for cancer therapy.

Since the approval of rituximab in 1997, monoclonal antibodies (mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target speci

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… Several decades later, Paul Ehrlich proposed the ‘magic bullet’ hypothesis, which suggested that drugs could be developed that were highly selective for pathogenic cells, thereby granting the drug high potency with minimal off-site toxicity 2 . … Delivery of toxic payloads (immunoconjugates) The use of mAbs to deliver a highly potent payload to tumor sites is perhaps the epitome of Ehrlich’s ‘magic bullet’ hypothesis. …

Current Challenges in Hematology: Awareness, Prevention, Equity.

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… Death rates have reduced across the various malignancy types, and rapidly fatal diseases, such as chronic myeloid leukemia, have become curable thanks to therapies like Imatinib Mesylate, occasionally termed an oral ‘magic bullet’ ( 1 – 3 ). …

Promising Highly Targeted Therapies for Cholangiocarcinoma: A Review and Future Perspectives.

To overcome the poor prognosis of cholangiocarcinoma (CCA), highly targeted therapies, such as antibody-drug conjugates (ADCs), photodynamic therapy (PDT) with/without systemic chemotherapy, and experimental photoimmunotherapy (PIT), have been developed. Three preclinical trials have investigated the use of ADCs targeting specific antigens, namely HER2, MUC1, and glypican-1 (GPC1), for CCA. Trastuzumab emtansine demonstrated higher antiproliferative activity in CCA cells expressing higher levels of HER2. Similarly, "staphylococcal enterotoxin A-MUC1 antibody" and "anti-GPC1 antibody-monomethyl

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… The first concept of ADC was proposed by Paul Enrlich as a “magic bullet” in 1910 [ 16 ], and the first successful conjugation of an antibody and a drug was realized by Mathe et al. in 1958 [ 17 ]. … Paul Ehrlich’s magic bullet concept: 100 years of progress. Nat. Rev. Cancer. 2008;8:473–480. doi: 10.1038/nrc2394. 17. Mathe G., Lou T.B., Bernard J. …

Advancements in antibody-drug conjugates as cancer therapeutics.

Antibody-drug conjugates (ADCs) represent a promising approach in targeted cancer therapy, combining the targeted precision of antibodies with the potency of cytotoxic payloads to selectively target tumour cell whilst minimising off-target effects. This review provides a comprehensive analysis of ADCs, encompassing their structural components, mechanisms of action, and clinical applications. It also examines recent technological advancements, particularly in antibody engineering and linker design, aimed at enhancing therapeutic efficacy and safety. The current clinical landscape is outlined, h

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… He described the use of antibodies as “magic bullets” due to their ability to specifically target diseased cells without harming healthy cells. 4 , 5 Ehrlich envisioned arming antibodies with toxins for selective destruction. … Paul Ehrlich’s magic bullet concept: 100 years of progress. Nat Rev Cancer. 2008;8(6):473–480. doi: 10.1038/nrc2394. 5. Schwartz R.S. Paul Ehrlich’s magic bullets. N Engl J Med. 2004;350(11):1079–1080. doi: 10.1056/NEJMp048021. 6. Ford C.H., Newman C.E., Johnson J.R., et al. …

Use of complementary and alternative medicine by patients with hematological diseases experience at a university hospital in northeast Mexico.

BackgroundComplementary and alternative medicine includes a diverse group of medical and healthcare systems, practices and products not considered part of conventional medicine. Although there is information on unconventional practices in oncological diseases, specific data regarding the use of complementary and alternative medicine by hematology patients is scarce.ObjectiveThe aim of this study is to document the prevalence of this modality of unconventional therapy in patients with malignant and benign hematological diseases, particularly children with acute lymphoblastic leukemia.MethodsAn

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… Alternative Medicine (CAM) consists of the use of any medical system, practice or products not considered a medical therapy by conventional western medicine as practiced by healthcare professionals holding a medical degree. ( 1 ) The underlying rationale for many of these therapies is based on a form of magical …

Преобразовательный потенциал липидных наночастиц, приспособленных для острой миэлоидной лейкемии.

Технологи, которые занимаются клетками, и инженерная клеточная терапия до сих пор не принесли таких же впечатляющих результатов в острой миэлоидной лейкемии (АМЛ), что и в других гематологическая малигнации. В ходе этого обзора мы анализируем проблемы, связанные с разработкой иммунотерапии для борьбы с отмыванием денег, включая целевую, неопухоль, синдром выброса цитокина (КРС) и «миелиоидный поглотитель». Затем мы обсуждаем появление двух технологий, которые могли бы решить основные проблемы, связанные с проведением расследований по борьбе с отмыванием денег: целенаправленные липидные наночас

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… The challenges of AML immunotherapy On-target, off-tumor toxicity A major obstacle of new cancer treatments is the rarity of truly tumor-specific targets for the “magic bullets” that have been sought intensely since they were envisioned by Paul Ehrlich in 1908 ( 8 ). … Paul Ehrlich's magic bullet concept: 100 years of progress . Nat Rev Cancer . ( 2008 ) 8 : 473–80 . doi: 10.1038/nrc2394 18469827 9 Appelbaum J Price AE Oda K Zhang J Leung WH Tampella G . Drug-regulated CD33-targeted CAR T cells control AML using clinically optimized rapamycin dosing . …

The advancement and utility of multimodal imaging in the diagnosis of degenerative disc disease.

Degenerative disc disease (DDD) is a common spinal condition characterized by the deterioration of intervertebral discs, leading to chronic back pain and reduced mobility. While magnetic resonance imaging (MRI) has long been the standard for late-stage DDD diagnosis, its limitations in early-stage detection prompt the exploration of advanced imaging methods. Positron emission tomography/computed tomography (PET/CT) using 18F- fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) has shown promise in identifying metabolic imbalances and age-related spinal degeneration, thereby complementing CT

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… Developing quantitative MRI (QMRI) techniques such as T2 star (T2*) mapping, T1ρ and T2 relaxation mapping with and without magic echo sequences, sodium MRI, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), glycosaminoglycan chemical exchange saturation transfer (gagCEST), MR Spectroscopy (MRS … Finally, a still emerging T2 pulse sequence termed “magic echo” has shown promise in boosting the sensitivity of T2 relaxation mapping for degenerative disc changes by elongating relaxation times compared to conventional spin echo. …

Keyword Index for Volume 100

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… 1589 liver metastasis 1540 liver resection 617 LKB1 370 LLL-3 106 LNcaP 1068 lomeguatrib 1245, 1250 longitudinal study 1558 Los Angeles 834 lung cancer 56, 167, 291, 464, 470, 941, 1037, 1336, 1896, 1949 lymph node metastasis 1937 lymphoid tumours 1926 lymphoma 524, 1771 macrophages 113 magic …

Cost analysis of childhood hematopoietic stem cell transplantation in Sichuan, China.

ObjectiveTo analyze the inpatient cost of hematopoietic stem cell transplantation (HSCT) in children, so as to support clinical decision-making.MethodsStudy population were children who received HSCT in a tertiary children's hospital (Sichuan, China) between 1st January 2020 and 31st December 2021. The median and interquartile range (IQR) of total cost at 100 days post transplantation were calculated. Subgroup analyses were conducted based on age, gender, transplantation types, and post-transplant complications. The cost differences between subgroups were analyzed to determine whether it had a

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… Complications were graded based on NCI Common Terminology Criteria for Adverse Events (CTCAE, version 4.03; Supplementary material ) grading scale ( 14 ) and the Mount Sinai Acute GvHD International Consortium (MAGIC) grading system ( Supplementary Figure 1 ) ( 15 , 16 ). …

Ten years of marketing approvals of anticancer drugs in Europe: regulatory policy and guidance documents need to find a balance between different pressures.

Despite important progress in understanding the molecular factors underlying the development of cancer and the improvement in response rates with new drugs, long-term survival is still disappointing for most common solid tumours. This might be because very little of the modest gain for patients is the result of the new compounds discovered and marketed recently. An assessment of the regulatory agencies' performance may suggest improvements. The present analysis summarizes and evaluates the type of studies and end points used by the EMEA to approve new anticancer drugs, and discusses the applic

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… There should be a very strong obligation for phase III trials unless we are lucky enough to have found a ‘magic bullet’, but these are very rare! The design of phase II studies should be improved to make sure that a positive result points to a real need for phase III studies. …

Targeted Hybrid Nanocarriers as Co-Delivery Systems for Enhanced Cancer Therapy.

Hybrid nanocarriers have realized a growing interest in drug delivery research because of the potential of being able to treat, manage or cure diseases that previously had limited therapy or cure. Cancer is currently considered the second leading cause of death globally. This makes cancer therapy a major focus in terms of the need for efficacious and safe drug formulations that can be used to reduce the rate of morbidity and mortality globally. The major challenge encountered over the years with cancer chemotherapy is the non-selectivity of anticancer drugs, leading to severe adverse effects i

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… occur homogeneously even within individual tumors. 22 Figure 1 Schematic representation of passive targeting of cancer cells via the enhanced permeability and retention effect (EPR) 23 Active targeting The concept of active targeting was first conceptualized by Paul Ehrlich with his idea of the “magic … “The magic bullet” ideology has to do with the idea that when a drug is administered, it should go directly to the required site of action without causing damage to other cells or tissues. 24 Active targeted drug delivery systems comprise three main constituents: the targeting moiety, the nanocarrier …