Search Results (5)

Breast cancer is a heterogeneous disease characterized by a wide range of biomarker expressions, resulting in varied progression, behavior, and prognosis. While traditional biopsy-based molecular classification is the gold standard, it is invasive and limited in capturing tumor heterogeneity, especially in deep or metastatic lesions. Molecular imaging, particularly positron emission tomography (PET) imaging, offering a non-invasive alternative, potentially plays a crucial role in the classification and management of breast cancer by providing detailed information about tumor location, heterogeneity, and progression. This narrative review, which focuses on both clinical patients and preclinical studies, explores the latest advancements in PET imaging for breast cancer, emphasizing the development of new tracers targeting hormone receptors such as the estrogen alpha receptor, progesterone receptor, androgen receptor, estrogen beta receptor, as well as the ErbB family of receptors, VEGF/VEGFR, PARP1, PD-L1, and markers for indirectly assessing Ki-67. These innovative radiopharmaceuticals have the potential to guide personalized treatment approaches based on the unique tumor profiles of individual patients. Additionally, they may improve the assessment of treatment efficacy, ultimately leading to better outcomes for those diagnosed with breast cancer. Full article

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with poor prognosis. Current endocrine therapy or anti HER-2 therapy is not available for these patients. Chemotherapeutic treatment response varies among patients due to the disease heterogeneity. To overcome these challenges, theranostics for treating TNBC have been widely investigated. Anticancer material conjugated nanoparticles with target-binding ligand and tracer agents enable simultaneous drug delivery and visualization of the lesion with minimal off-target toxicity. In this review, we summarize recently FDA-approved targeted therapies for TNBC, such as poly-ADP-ribose polymerase (PARP) inhibitors, check point inhibitors, and antibody-drug conjugates. Particularly, novel theranostic approaches including lipid-based, polymer-based, and carbon-based nanocarriers are discussed, which can provide basic overview of nano-therapeutic modalities in TNBC diagnosis and treatment. Full article

The compound β-lapachone, a naturally derived naphthoquinone, has been utilized as a potent medicinal nutrient to improve health. Over the last twelve years, numerous reports have demonstrated distinct associations of β-lapachone and NAD(P)H: quinone oxidoreductase 1 (NQO1) protein in the amelioration of various diseases. Comprehensive research of NQO1 bioactivity has clearly confirmed the tumoricidal effects of β-lapachone action through NAD⁺-keresis, in which severe DNA damage from reactive oxygen species (ROS) production triggers a poly-ADP-ribose polymerase-I (PARP1) hyperactivation cascade, culminating in NAD⁺/ATP depletion. Here, we report a novel combination strategy with aminooxyacetic acid (AOA), an aspartate aminotransferase inhibitor that blocks the malate-aspartate shuttle (MAS) and synergistically enhances the efficacy of β-lapachone metabolic perturbation in NQO1⁺ breast cancer. We evaluated metabolic turnover in MDA-MB-231 NQO1⁺, MDA-MB-231 NQO1⁻, MDA-MB-468, and T47D cancer cells by measuring the isotopic labeling of metabolites from a [U-¹³C]glucose tracer. We show that β-lapachone treatment significantly hampers lactate secretion by ~85% in NQO1⁺ cells. Our data demonstrate that combinatorial treatment decreases citrate, glutamate, and succinate enrichment by ~14%, ~50%, and ~65%, respectively. Differences in citrate, glutamate, and succinate fractional enrichments indicate synergistic effects on central metabolism based on the coefficient of drug interaction. Metabolic modeling suggests that increased glutamine anaplerosis is protective in the case of MAS inhibition. Full article

Metastatic castration-resistant prostate cancer (mCRPC) represents a condition of progressive disease in spite of androgen deprivation therapy (ADT), with a broad spectrum of manifestations ranging from no symptoms to severe debilitation due to bone or visceral metastatization. The management of mCRPC has been profoundly modified by introducing novel therapeutic tools such as antiandrogen drugs (i.e., abiraterone acetate and enzalutamide), immunotherapy through sipuleucel-T, and targeted alpha therapy (TAT). This variety of approaches calls for unmet need of biomarkers suitable for patients’ pre-treatment selection and prognostic stratification. In this scenario, imaging with positron emission computed tomography (PET/CT) presents great and still unexplored potential to detect specific molecular and metabolic signatures, some of whom, such as the prostate specific membrane antigen (PSMA), can also be exploited as therapeutic targets, thus combining diagnosis and therapy in the so-called “theranostic” approach. In this review, we performed a web-based and desktop literature research to investigate the prognostic and theranostic potential of several PET imaging probes, such as ¹⁸F-FDG, ¹⁸F-choline and ⁶⁸Ga-PSMA-11, also covering the emerging tracers still in a pre-clinical phase (e.g., PARP-inhibitors’ analogs and the radioligands binding to gastrin releasing peptide receptors/GRPR), highlighting their potential for defining personalized care pathways in mCRPC Full article

The central paradigm of novel therapeutic approaches in cancer therapy is identifying and targeting molecular biomarkers. One such target is the nuclear DNA repair enzyme Poly-(ADP ribose) polymerase 1 (PARP1). Sensitivity to PARP inhibition in certain cancers such as gBRCA^mut breast and ovarian cancers has led to its exploitation as a target. The overexpression of PARP1 in several types of cancer further evoked interest in its use as an imaging target. While PARP1-targeted inhibitors have fast developed and approved in this past decade, determination of PARP1 expression might help to predict the response to PARP inhibitor treatment. This has the potential of improving prognosis and moving towards tailored therapy options and/or dosages. This review summarizes the recent pre-clinical advancements in imaging and theranostic PARP1 targeted tracers. To assess PARP1 levels, several imaging probes with fluorescent or beta/gamma emitting radionuclides have been proposed and three have advanced to ongoing clinical evaluation. Apart from its diagnostic value in detection of primary tumors as well as metastases, this shall also help in delivering therapeutic radionuclides to PARP1 overexpressing tumors. Henceforth nuclear medicine has now advanced towards conjugating theranostic radionuclides to PARP1 inhibitors. This paves the way for a future of PARP1-targeted theranostics and personalized therapy. Full article