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G Protein-Coupled Receptor Signaling: Implications and Therapeutic Development Advances in Cancers.

G protein-coupled receptors (GPCRs) are the largest and most diverse class of membrane proteins, mediating cellular responses to a wide range of extracellular stimuli. GPCRs initiate complex intracellular signaling networks that regulate vital physiological functions and are associated with numerous diseases, including various types of cancer. Their conserved seven-transmembrane (7TM) structure enables these signaling networks by allowing interactions with multiple ligands and intracellular effectors. In several types of tumors, abnormal GPCR signaling promotes carcinogenesis by supporting imm

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… Raloxifene | ER | Breast cancer | Small molecule | 2014 | [ 314 ] Sonidegib (Odomzo) | SMO | Locally advanced and metastatic basal‐cell carcinoma | Small molecule | 2015 | [ 315 ] Mogamulizumab | CCR4 | Cutaneous/peripheral T‐cell lymphoma; adult T‐cell lymphoma | mAb | 2018 | [ 294 , 316 ] Lutathera (Lutetium … Lu 177 dotatate) | SSTR | Gastroenteropancreatic neuroendocrine tumors (GEP‐NETs) | Peptide | 2018 | [ 317 ] Gilteritinib | Serotonin receptors | Relapsed or refractory acute myeloid leukemia | Small molecule | 2018 | [ 318 ] Lutetium 177 dotatate | SSTR2 | Gastroenteropancreatic neuroendocrine tumors …

Role of PET/CT and Therapy Management of Pancreatic Neuroendocrine Tumors.

Pancreatic neuroendocrine neoplasms (panNENs) are heterogeneous neoplasms with neuroendocrine differentiation that show peculiar clinical and histomorphological features, with variable prognosis. In recent years, advances in knowledge regarding the pathophysiology and heterogeneous clinical presentation, as well as the availability of different diagnostic procedures for panNEN diagnosis and novel therapeutic options for patient clinical management, has led to the recognition of the need for an active multidisciplinary discussion for optimal patient care. Molecular imaging with positron emissio

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… first-line diagnostic procedure for staging or restaging any non-insulinoma panNET case for detection of the unknown primary tumor site or early relapse, and for evaluation of in vivo SRE to select patients candidate for peptide receptor radiometabolic treatment (PRRT) with 90 Y (Yttrium-90) or 177 Lu (Lutetium …

Mechanical suppression of osteolytic bone metastases in advanced breast cancer patients: a randomised controlled study protocol evaluating safety, feasibility and preliminary efficacy of exercise as a targeted medicine.

BACKGROUND: Skeletal metastases present a major challenge for clinicians, representing an advanced and typically incurable stage of cancer. Bone is also the most common location for metastatic breast carcinoma, with skeletal lesions identified in over 80% of patients with advanced breast cancer. Preclinical models have demonstrated the ability of mechanical stimulation to suppress tumour formation and promote skeletal preservation at bone sites with osteolytic lesions, generating modulatory interference of tumour-driven bone remodelling. Preclinical studies have also demonstrated anti-cancer e

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… Banerjee S Pillai M Knapp F Lutetium-177 therapeutic radiopharmaceuticals: linking chemistry, radiochemistry, and practical applications Chem Rev 2015 115 8 2934 2974 10.1021/cr500171e 25865818 25. …

Spiegelmer Aptamers: Innovative Approach in Breast Cancer.

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide, emphasizing the urgent need for improved diagnostic and therapeutic strategies. Aptamers which are synthetic oligonucleotides that specifically bind to target molecules, offer high affinity, low immunogenicity, and superior tumor penetration compared to antibodies. However, their clinical translation has been limited by instability in biological systems. Spiegelmers, a novel class of mirror-image aptamers composed of L-nucleotides, overcome this limitation through intrinsic nuclease resistance an

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… Theranostics have demonstrated promising clinical outcomes. 89 For example, one study utilized trastuzumab conjugated to the bifunctional chelator DOTA, labeled with lutetium-177 (Lu-177), for SPECT/CT imaging to specifically identify HER2-positive patients. 90 Therefore, further research is needed …

Current Status of 68Ga-Pentixafor in Solid Tumours.

Chemokine receptor CXCR4 is overexpressed in neoplasms and its expression is related to tumour invasion, metastasis and aggressiveness. 68Ga-Pentixafor is used to non-invasively image the expression of CXCR4 in tumours and has been widely used in haematological malignancies. Recent evidence shows that therapies targeting CXCR4 can increase the chemosensitivity of the tumour as well as inhibit tumour metastasis and aggressiveness. 68Ga-Pentixafor has shown promise as an elegant radiotracer to aid in the selection of patients whose tumours demonstrate CXCR4 overexpression and who therefore may b

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… Pentixafor is a peptide that targets CXCR4 and a theranostic agent capable of being labelled with Gallium-68 (Ga-68) for positron emission tomography (PET) imaging, and Lutetium-177 (Lu-177) for therapy [ 5 ]. …

Polypharmacy and medication use in patients with chronic kidney disease with and without kidney replacement therapy compared to matched controls.

BackgroundThis study aims to examine polypharmacy (PP) prevalence in patients with chronic kidney disease (CKD) Stage G4/G5 and patients with kidney replacement therapy (KRT) compared with matched controls from the general population. Furthermore, we examine risk factors for PP and describe the most commonly dispensed medications.MethodsDutch health claims data were used to identify three patient groups: CKD Stage G4/G5, dialysis and kidney transplant patients. Each patient was matched to two controls based on age, sex and socio-economic status (SES) score. We differentiated between 'all medic

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… ATC code | Name L01AX04 | Dacarbazine L01BB02 | Mercaptopurine L01BB03 | Tioguanine L01BC02 | Fluorouracil L03AC01 | Aldesleukine V10XX04 | lutetium Oxotreotide Table A6. DDDs for central nervous system disorders: multiple sclerosis milIU, million international units. …

Targeted Alpha Therapy: Progress in Radionuclide Production, Radiochemistry, and Applications.

This review outlines the accomplishments and potential developments of targeted alpha (α) particle therapy (TAT). It discusses the therapeutic advantages of the short and highly ionizing path of α-particle emissions; the ability of TAT to complement and provide superior efficacy over existing forms of radiotherapy; the physical decay properties and radiochemistry of common α-emitters, including 225Ac, 213Bi, 224Ra, 212Pb, 227Th, 223Ra, 211At, and 149Tb; the production techniques and proper handling of α-emitters in a radiopharmacy; recent preclinical developments; ongoing and completed clinica

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… Single-Dose Anti-CD138 radioimmunotherapy: Bismuth-213 is more efficient than lutetium-177 for treatment of multiple myeloma in a preclinical model Front. Med. 2015 2 76 10.3389/fmed.2015.00076 26582128 PMC4631990 97. McDevitt M.R. Barendswaard E. Ma D. Lai L. Curcio M.J. Sgouros G. …

Smart Targeting To Improve Cancer Therapeutics.

Cancer is the second largest cause of death worldwide with the number of new cancer cases predicted to grow significantly in the next decades. Biotechnology and medicine can and should work hand-in-hand to improve cancer diagnosis and treatment efficacy. However, success has been frequently limited, in particular when treating late-stage solid tumors. There still is the need to develop smart and synergistic therapeutic approaches to achieve the synthesis of strong and effective drugs and delivery systems. Much interest has been paid to the development of smart drug delivery systems (drug-loade

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… Anaplastic thyroid cancer | Novartis Acalabrutinib | Calquence ® | Bruton tyrosine kinase inhibitor | Mantle cell lymphoma | AstraZeneca Niraparib | Zejula ® | Poly ADP ribose polymerase inhibitor | Ovarian cancer | Tesaro Apalutamide | Erleada ® | Androgens hormone inhibitor | Prostate cancer | Janssen Lutetium …

Radiolabeled Peptides and Antibodies in Medicine.

Radiolabeled peptides are a relatively new, very specific radiotracer group, which is still expanding. This group is very diverse in terms of peptide size. It contains very small structures containing several amino acids and whole antibodies. Moreover, radiolabeled peptides are diverse in terms of the binding aim and therapeutic or diagnostic applications. The majority of this class of radiotracers is utilized in oncology, where the same structure can be used in therapy and diagnostic imaging by varying the radionuclide. In this study, we collected new reports of radiolabeled peptide applicati

Precision-Engineered CD3 T-Cell Engagers for Solid Tumours: Conditional Activation, Microenvironment Modulation, and Clinical Translation.

BackgroundT-cell-engaging bispecific antibodies (TCEs) have transformed haematological malignancy treatment (blinatumomab > 40% complete remission), yet solid tumour efficacy remains limited (MethodsReview of 55 phase I-III trials of CD3-based TCEs in solid tumours, including tarlatamab (DLL3-targeted, small-cell lung cancer) and xaluritamig (STEAP1-targeted, prostate cancer). Analysis of next-generation engineering strategies and resistance mechanisms via genomic and immunohistochemical data.ResultResponse rates now approach ~40% in selected settings, marking an inflection point. In extensive

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… Metastatic Castration-Resistant Prostate Cancer The mCRPC landscape has expanded: AR pathway inhibitors, PARP inhibitors, and lutetium-177 PSMA radioligand therapy. …

EANM guidelines on the use of [18F]FDG PET/CT in diagnosis, staging, prognostication, therapy assessment, and restaging of plasma cell disorders.

We provide updated guidance and standards for the indication, acquisition, and interpretation of [18F]FDG PET/CT for plasma cell disorders. Procedures and characteristics are reported and different scenarios for the clinical use of [18F]FDG PET/CT are discussed. This document provides clinicians and technicians with the best available evidence to support the implementation of [18F]FDG PET/CT imaging in routine practice and future research.

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… The first clinical results with lutetium-177 or yttrium-90 based CXCR4 radionuclide therapy in patients with good target expression demonstrated by CXCR4 PET support the further development of this treatment strategy [ 99 ]. …

Prostate cancer immunotherapy-based strategies: an updated review emphasizing immune checkpoint inhibitors.

Prostate cancer (PC) is one of the most common cancers that is diagnosed in about 10-15% of men in old age. It seems that the current treatments are not effective, and this leads to prostate cancer becoming the second-deadliest cancer. Treatments such as chemotherapy, radiotherapy, androgen deprivation therapy (ADT), and surgery are among these treatments. However, the possibility of disease recurrence after these treatments is high. Therefore, other methods have become necessary, and PC treatment is changing. One of the methods that has received much attention today is immunotherapy. Immunoth

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… Phase 1/2 study of fractionated dose lutetium-177–labeled anti–prostate-specific membrane antigen monoclonal antibody J591 (177Lu-J591) for metastatic castration-resistant prostate cancer. Cancer. (2019) 125:2561–9. doi: 10.1002/cncr.32072 113. …

Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium.

The medical history of cancer began millennia ago. Historical findings of patients with cancer date back to ancient Egyptian and Greek civilizations, where this disease was predominantly treated with radical surgery and cautery that were often ineffective, leading to the death of patients. Over the centuries, important discoveries allowed to identify the biological and pathological features of tumors, without however contributing to the development of effective therapeutic approaches until the end of the 1800s, when the discovery of X-rays and their use for the treatment of tumors provided the

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… Finally, other radiopharmaceuticals are used for the treatment of cancer, including Phosphorus-32, Yttrium-90 spheres for the treatment of colorectal liver metastasis, 131I-MIBG meta-iodo-benzylguanidine for the treatment of phaeochromocytoma and neuroblastoma, and Yttrium-90 and Lutetium-177 for the …

Nanobodies for Medical Imaging: About Ready for Prime Time?

Recent advances in medical treatments have been revolutionary in shaping the management and treatment landscape of patients, notably cancer patients. Over the last decade, patients with diverse forms of locally advanced or metastatic cancer, such as melanoma, lung cancers, and many blood-borne malignancies, have seen their life expectancies increasing significantly. Notwithstanding these encouraging results, the present-day struggle with these treatments concerns patients who remain largely unresponsive, as well as those who experience severely toxic side effects. Gaining deeper insight into t

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… short half-lives for imaging, such as Galium-68 ( 68 Ga, t 1/2 = 67.71 min) and 18 F (t 1/2 = 109.7 min), as well as longer-lived isotopes, such as Technetium-99m ( 99m Tc t 1/2 = 6.0 h), Copper-64 ( 64 Cu t 1/2 = 12.7 h), Indium-111 ( 111 In t 1/2 = 67.2 h), Zirconium-89 ( 89 Zr t 1/2 = 78.41 h), and Lutetium …

Clinical Posters From JADPRO Live 2024

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Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.

Reactive oxygen species (ROS) act as critical secondary messengers in various intracellular signaling pathways that regulate cellular proliferation, differentiation, and survival under normal physiological conditions. However, dysregulation of redox signaling-driven by genetic mutations, epigenetic alterations, and posttranscriptional or posttranslational modifications-plays a central role in malignant transformation and cancer progression. Cancer cells typically exhibit elevated basal ROS levels due to increased metabolic activity, mitochondrial dysfunction, and oncogene activation. This mode

Metastatic Spread in Prostate Cancer Patients Influencing Radiotherapy Response.

Radiotherapy and surgery are curative treatment options for localized prostate cancer (PCa) with a 5-year survival rate of nearly 100%. Once PCa cells spread into distant organs, such as bone, the overall survival rate of patients drops dramatically. The metastatic cascade and organotropism of PCa cells are regulated by different cellular subtypes, organ microenvironment, and their interactions. This cross-talk leads to pre-metastatic niche formation that releases chemo-attractive factors enforcing the formation of distant metastasis. Biological characteristics of PCa metastasis impacting on m

Bispecific Antibody-Based Immune-Cell Engagers and Their Emerging Therapeutic Targets in Cancer Immunotherapy.

Cancer is the second leading cause of death worldwide after cardiovascular diseases. Harnessing the power of immune cells is a promising strategy to improve the antitumor effect of cancer immunotherapy. Recent progress in recombinant DNA technology and antibody engineering has ushered in a new era of bispecific antibody (bsAb)-based immune-cell engagers (ICEs), including T- and natural-killer-cell engagers. Since the first approval of blinatumomab by the United States Food and Drug Administration (US FDA), various bsAb-based ICEs have been developed for the effective treatment of patients with

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… Phase 1/2 study of fractionated dose lutetium-177–labeled anti–prostate-specific membrane antigen monoclonal antibody J591 (177Lu-J591) for metastatic castration-resistant prostate cancer. Cancer. 2019;125:2561–2569. doi: 10.1002/cncr.32072. 92. …

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

Targeting Tumor Glycans for Cancer Therapy: Successes, Limitations, and Perspectives.

Aberrant glycosylation is a hallmark of cancer and can lead to changes that influence tumor behavior. Glycans can serve as a source of novel clinical biomarker developments, providing a set of specific targets for therapeutic intervention. Different mechanisms of aberrant glycosylation lead to the formation of tumor-associated carbohydrate antigens (TACAs) suitable for selective cancer-targeting therapy. The best characterized TACAs are truncated O-glycans (Tn, TF, and sialyl-Tn antigens), gangliosides (GD2, GD3, GM2, GM3, fucosyl-GM1), globo-serie glycans (Globo-H, SSEA-3, SSEA-4), Lewis anti