Development Of Drug Resistance Research Articles

CircTTC13 promotes sorafenib resistance in hepatocellular carcinoma through the inhibition of ferroptosis by targeting the miR-513a-5p/SLC7A11 axis

The high mortality rate from hepatocellular carcinoma (HCC) is due primarily to challenges in early diagnosis and the development of drug resistance in advanced stages. Many first-line chemotherapeutic drugs induce ferroptosis, a form of programmed cell death dependent on ferrous iron-mediated oxidative stress, suggesting that drug resistance and ensuing tumor progression may in part stem from reduced ferroptosis. Since circular RNAs (circRNAs) have been shown to influence tumor development, we examined whether specific circRNAs may regulate drug-induced ferroptosis in HCC. Through circRNA sequencing, we identified a novel hsa_circ_0000195 (circTTC13) that is overexpressed in HCC tissues. This overexpression is linked to higher tumor grade, more advanced tumor stage, decreased ferroptosis, and poorer overall survival. Overexpression of CircTTC13 in HCC cell lines and explant tumors was associated with increased proliferation rates, enhanced metastatic capacity, and resistance to sorafenib, while also inhibiting ferroptosis. Conversely, circTTC13 silencing reduced malignant characteristics and promoted ferroptosis. In silico analysis, luciferase assays, and fluorescence in situ hybridization collectively demonstrated that circTTC13 directly targets and reduces miR-513a-5p expression, which in turn leads to the upregulation of the negative ferroptosis regulator SLC7A11. Moreover, the inhibition of SLC7A11 mirrored the effect of circTTC13 knockdown, whereas ferroptosis inhibition mimicked the effect of circTTC13 overexpression. Both circTTC13 and SLC7A11 were highly expressed in drug-resistant HCC cells, and circTTC13 silencing induced ferroptosis and reversed sorafenib resistance in explant tumors. These findings identify circTTC13 as a critical driver of HCC progression and resistance to drug-induced ferroptosis via upregulation of SLC7A11. The cicTTC13/miR-513a-5p/SLC7A11 axis represents a potential therapeutic target for HCC.

Dysfunctional mitochondrial bioenergetics sustains drug resistance in cancer cells.

Resistance to drugs is one of the major issues affecting the response to pharmacological treatments for tumors. Different mechanisms have been proposed to explain the development of cancer drug resistance (CDR), and several approaches to overcome it have been suggested. However, the biological basis of CDR remains unclear. Here, we investigated whether mitochondrial damage and consequent mitochondrial dysfunction are major causes of drug resistance in different tumors. To this end, we used cell lines from three tumors: hepatocellular carcinoma, breast cancer, and colon cancer. We then applied a protocol that recapitulates chemotherapy regimens in patients, rendering each cell line resistant to the drug commonly used in their respective treatments. The combination of cellular respiration analysis, gene expression analysis of cytochrome c oxidase isoforms, and mass spectrometry assessment of cardiolipin reveals that mitochondrial dysfunction is the underlying cause of the resistant phenotype. Importantly, we disclosed for the first time the rapid inhibition of oxidative phosphorylation (OXPHOS) by L-lactate, the major product of fermentation. Finally, we demonstrated that inhibition of lactic acid fermentation and activation of OXPHOS can increase drug sensitivity in all tested drug-resistant cancer cells. Taken together, our results suggest that inhibiting fermentation and enhancing mitochondrial function in cancer cells may be a concrete option to control the worrisome phenomenon of CDR.

Novel inhibitors of the (VIBVN) NAT protein identified through pharmacophore modeling

Arylamine N-acetyltransferases (NATs, E.C. 2.3.1.5) constitute a family of phase II drug metabolizing enzymes. These enzymes catalyze the transfer of acetyl groups from acetyl-CoA to a variety of substrates including arylamines, arylhydrazines, and N-hydroxyarylamines. By facilitating these reactions, NATs play a pivotal role in the detoxification and metabolic processing of a wide range of drugs and carcinogens. NAT in marine V. vulnificus plays a role in the metabolism of drugs, leading to the development of drug resistance in marine V. vulnificus. However, inhibitors targeted marine V. vulnificus NAT [(VIBVN)NAT] remain unclear. Therefore, our research aimed to identify potential hit compounds that target (VIBVN)NAT. We integrated multiple computational approaches to screen for effective inhibitors. From this process, we identified two hit compounds, AK-968-11563024 and AG-205-36710025, with IC50 values of 18.86 µM and 33.27 µM, respectively. Molecular dynamics simulations further elucidated the binding mechanism between (VIBVN)NAT and AK-968-11563024. Our study revealed that AK-968-11563024 forms stable interactions with PHE124, HIS167, and TRP230, which may contribute to its biological activity. Our findings provide a valuable foundation for the future development of drugs targeted therapeutics against (VIBVN)NAT.

Drug combination assays using Caenorhabditis elegans as a model system.

The C. elegans drug combination assay evaluates the effects of drug combinations in the nematode Caenorhabditis elegans, serving as a valuable tool to assess the efficacy of pharmaceutical agents and natural compounds. Using C. elegans as a model organism, this method allows for the efficient screening of the combined effects of different drugs and evaluation of synergistic effects in drug combinations, which reduces the risk of developing drug resistance. Combination therapy, involving commercial drugs, new agents, or natural products, broadens treatment effectiveness by targeting multiple pathways, effectively managing complex diseases with minimized side effects. The method focuses on discovering effective drug combinations, such as anthelmintic drugs, streamlining early-stage drug discovery to save time and resources. Additionally, its versatility allows for application across most areas of pharmacology and toxicology, extending its usefulness beyond anthelmintic treatments. In the experiments, synchronized worms are exposed to different drug concentrations to evaluate behavioral changes, mostly alterations in worm locomotion. Concentration-response curves for changes in behavior are generated and EC50 or IC50 values determined for the individual drugs. To determine whether the effects of a drug combination are synergistic, additive, or antagonistic, at least three different concentration ratios must be tested. These combinations are then analyzed using specialized drug combination analysis software. This methodology ensures consistent and precise outcomes and evaluates drug impacts on worm behavior parameters crucial for effective pharmacological activity. In conclusion, the C. elegans drug combination assay provides critical insights for developing successful market formulations applicable across a wide range of pharmacological treatments. Its ability to efficiently screen for synergistic, additive, or antagonistic effects makes it a valuable tool for identifying effective therapeutic strategies, potentially reducing drug resistance and improving treatment outcomes in various medical and toxicological fields.

Global dissemination of Klebsiella pneumoniae in surface waters: Genomic insights into drug resistance, virulence, and clinical relevance.

The aquatic environment is a major pathway for the spread of antibiotic resistance (AR) among microorganisms. Among these, Klebsiella pneumoniae reveals high genome plasticity, adaptability, and the ability to colonize humans, animals, and the natural environment, awarding it a significant role in the spread of AR. This work presents an in-depth analysis of the whole sequences of 149 K. pneumoniae genomes isolated from surface waters available in databases. The sequences were obtained from 20 countries in five continents. The analyses showed a high genomic diversity of isolates, classifying them into 94 unique sequence types. The isolates carried numerous virulence and drug resistance determinants in their genomes, including genes for carbapenem and colistin resistance. The critical resistance genes were located on plasmids, indicating their high mobility and ease of access in water environments. Sublineage 258 members, in particular ST11, have been identified as important carriers of both important drug resistance determinants and key virulence factors, thus posing a substantial threat to human health. Our analysis revealed the direct transmission of drug-resistant and virulent clinical strains to the natural environment, highlighting the role of K. pneumoniae in the dissemination of drug resistance within the "One Health" framework. Surface waters represent an environment conducive to the spread and evolution of drug resistance, and K. pneumoniae plays a significant role in this process by providing clinically-significant antibiotic resistance genes to environmental recipients.

Hypotheses of development and strategies for overcoming drug resistance in epilepsy. Part I: Hypotheses of development

Currently, the problem of effective therapy for drug-resistant epilepsy remains vastly relevant. The severity of drug-resistant epilepsy, remarkable negative social sequelae and sudden death in epilepsy pose a heavy burden on healthcare system. Although many innovative antiepileptic drugs have been developed in recent decades, surgical approach remains the only effective way to treat drug-resistant epilepsy which is coupled to significant health risks and does not guarantee freedom from seizures. The stumbling block in managing this pathology is the lack of knowledge on pathogenetic mechanisms, leaving a significant proportion of patients without quality medical care. There are different viewpoints on developing drug resistance in epilepsy, which are characterized by multilayered and overlapping molecular disease bases. The review presents the analysis of the existing hypotheses regarding the mechanisms underlying drug resistance development in epilepsy.

In Vivo and In Vitro Studies Assessing the Antiviral Efficacy of Double Combinations Against Coxsackievirus B Infection.

Coxsackievirus B (CVB) infections, ranging from mild to severe diseases, lack specific antiviral treatments, underscoring the need for novel therapeutic strategies. Drug therapy is an important tool for controlling enterovirus infections, but clinically effective drugs do not currently exist, mainly due to the development of drug resistance. Combination therapy with two or more drugs has the potential to successfully inhibit viral infection more effectively than either drug alone as well as delay the development of resistance. This study explores the consecutive alternating administration (CAA) scheme in mice with CVB1 infection, utilizing double antiviral combinations consisting of pleconaril and MDL-860, with guanidine hydrochloride and oxoglaucine. The CAA combinations of pleconaril achieved a survival rate, in infected mice, of up to 59%, while the combinations of MDL-860 showed no significant effects. CAA reduced mortality, prolonged mean survival time (up to 5 days), and mitigated drug resistance compared to monotherapy or simultaneous administration. Monotherapeutic courses and daily administration of double combinations had no effect. Phenotypic characterization using the IC50 marker of virus isolates from brain tissue of infected and treated mice was of particular importance for the evaluation of the CAA treatment scheme. The results show increased susceptibility of the virus isolates to the partner compounds in double CAA combinations. In contrast, virus isolates from the monotherapeutic groups manifested a diminished susceptibility to their respective compound, which signals the development of drug resistance. All data obtained prove the potential of the CAA scheme for the development of effective chemotherapy of enterovirus infections.

The Evolution of Antimicrobial Resistance in Acinetobacter baumannii and New Strategies to Fight It.

Acinetobacter baumannii is considered one of the prioritized ESKAPE microorganisms for the research and development of novel treatments by the World Health Organization, especially because of its remarkable persistence and drug resistance. In this review, we describe how this can be acquired by the enzymatic degradation of antibiotics, target site modification, altered membrane permeability, multidrug efflux pumps, and their ability to form biofilms. Also, the evolution of drug resistance in A. baumannii, which is mainly driven by mobile genetic elements, is reported, with particular reference to plasmid-associated resistance, resistance islands, and insertion sequences. Finally, an overview of existing, new, and alternative therapies is provided.

Synthetic Vesicle-Based Drug Delivery Systems for Oral Disease Therapy: Current Applications and Future Directions.

Oral diseases such as dental caries, periodontitis, and oral cancer are prevalent and present significant challenges to global public health. Although these diseases are typically treated through procedures like dental preparation and resin filling, scaling and root planning, or surgical excision, these interventions are often not entirely effective, and postoperative drug therapy is usually required. Traditional drug treatments, however, are limited by factors such as poor drug penetration, significant side effects, and the development of drug resistance. As a result, there is a growing need for novel drug delivery systems that can enhance therapeutic efficacy, reduce side effects, and improve treatment outcomes. In recent years, drug-loaded vesicles, such as liposomes, polymersomes, and extracellular vesicles (EVs), have emerged as promising drug delivery platforms due to their high drug encapsulation efficiency, controlled release properties, and excellent biocompatibility. This review provides an in-depth examination of the characteristics, advantages, and limitations of liposomes, polymersomes, and extracellular vesicles in the context of oral disease treatment. It further explores the reasons for their advantages and limitations and discusses the specific applications, development prospects, and strategies for optimizing these vesicle-based systems for improved clinical outcomes.

Bioactive Products Targeting C-Met As Potential Antitumour Drugs.

With increasing duration of treatment, many tumours gradually develop drug resistance. Therefore, novel antitumour drugs need to be developed to treat patients with tumours. Targeting c-met inhibitors may be an effective treatment strategy. Scientific databases such as ScienceDirect, PubMed, the Wiley Online Library, and Social Sciences Citation Index were used to collect information. All the relevant literature was reviewed, and the available literature was screened. The upstream and downstream pathways of c-Met and their relevance to antitumour effects were searched based on the articles' title, abstract, and full text. The c-Met-targeting drugs with antitumour effects are summarized below. A "citation within a citation" or snowballing approach was used in this screening process to identify additional papers that may have been missed in the initial literature screening process. High-quality studies published in peer-reviewed journals were summarized and prioritized for citation in the review. In recent years, research on small-molecule targeted drugs has developed rapidly. Many results have also been achieved in the synthesis and isolation of c-Met inhibitors from natural compounds and traditional Chinese medicines. This article summarizes the developments in anti-c-Met drugs, which are synthesized and isolated from natural compounds and traditional Chinese medicine (TCM). This study provides primary resources for the development of c-Met inhibitors.

Structural Modifications and Prospects of Histone Deacetylase (HDAC) Inhibitors in Cancer.

Histone deacetylases (HDACs) play a crucial role in the regulation of cancer progression and have emerged as key targets for antitumor therapy. Histone Deacetylase Inhibitors (HDACis) effectively suppress tumor cell proliferation, induce apoptosis, and cause cell cycle arrest, demonstrating broad-spectrum antitumor activity. This article primarily focuses on enhancing the selectivity of HDACis through structural modification using natural compounds. It provides detailed insights into the structure modification of histone deacetylase 8 (HDAC8) and histone deacetylase 10 (HDAC10), as well as dual-- target inhibitors and their pharmacological effects. Furthermore, conventional HDAC inhibitors are susceptible to off-target effects and the development of drug resistance. Our research focuses on augmenting the targeting specificity of HDAC inhibitors through their combination with proteolysis targeting chimera (PROTAC). Lastly, the latest advancements in clinical research on HDAC inhibitors were summarized, revealing that these inhibitors possess limitations in their clinical applications due to intrinsic or acquired resistance. Consequently, this article primarily focuses on summarizing the current status and prospects of structural modifications for HDAC inhibitors, with the aim of inspiring researchers to develop novel HDAC inhibitors exhibiting enhanced activity for improved application in clinical research.

Bis-3-chloropiperidines: a novel motif for anthelmintic drug design.

Parasites account for huge economic losses by infecting agriculturally important plants and animals. Furthermore, morbidity and death caused by parasites affect a large part of the world population, especially in economically weak regions. Anthelmintic drugs to tackle this challenge remain scarce and their efficiency becomes increasingly endangered by the advent of drug resistance development. In the present study, we assessed the anthelmintic potential of bis-3-chloropiperidines, a family of compounds which have already demonstrated antiproliferative activity against various cell lines. We synthesized and tested the activity of 21 bis-3-chloropiperidine derivatives against two strains of the free-living nematode Caenorhabditis elegans (N2 and DC19) and the parasitic flatworm Schistosoma mansoni. Overall, bifunctional chloropiperidines featuring an aromatic linker performed best against the tested indicator organisms and could be considered for future optimization efforts. Ultimately, out of the 21 analyzed bis-3-chloropiperidines, four derivatives (2, 5, 9 and 11) reduced vitality parameters against S. mansoni and five the motility of C. elegans (2, 4, 5, 13, 21) while exhibiting no or low cytotoxicity.

Safety and efficacy of long-acting cabotegravir/rilpivirine versus standard oral antiretroviral therapy: a systematic review and meta-analysis.

In 2023, there were 39.9 million people living with HIV (PLWH) worldwide and 630 000 deaths related to HIV. New strategies are needed, and long-acting antiretrovirals (LAAs) are now widely considered to have great potential to help end the HIV epidemic. This systematic review and meta-analysis compare the safety and efficacy of LAA versus standard oral treatment (SOT) for HIV. PubMed and Embase databases, supplemented by ClinicalTrials.gov and grey literature, were searched. Randomized controlled trials (RCTs) reporting efficacy and/or safety of LAA versus SOT for PLWH until June 2024 were included. Efficacy (HIV RNA < 50 copies/mL) and HIV RNA ≥ 50 copies/mL, adverse events (AEs), treatment discontinuation, CD4 count, metabolic parameters and drug resistance were assessed. Prespecified subgroup analyses were conducted. The risk of bias was assessed with Cochrane RoB 2.0. Certainty of evidence was assessed using GRADE. Six RCTs were eligible for inclusion, involving 2829 participants. LAA was non-inferior to SOT in suppressing HIV RNA < 50 copies/mL [Risk Difference (RD), -0.00; 95% CI, -0.03-0.02; P = 0.83; I2 = 51%; high quality of evidence (QoE)]. LAA was associated with higher drug resistance (percentage pooled estimate, 57%; 95% CI, 33%-78% versus 9%; 95% CI, 2%-30%; moderate QoE) and risk of grade 1-4 AEs than SOT [Risk Ratio (RR), 1.22; 95% CI, 1.12-1.33; P < 0.001; I2 = 62%; moderate QoE]. LAA has non-inferior efficacy compared to SOT. However, participants receiving LAA were at a higher risk of developing drug resistance, cross-resistance and AEs.

Isoferulic acid facilitates effective clearance of hypervirulent Klebsiella pneumoniae through targeting capsule.

Hypervirulent Klebsiella pneumoniae (hvKP) poses an alarming threat in clinical settings and global public health owing to its high pathogenicity, epidemic success and rapid development of drug resistance, especially the emergence of carbapenem-resistant lineages (CR-hvKP). With the decline of the "last resort" antibiotic class and the decreasing efficacy of first-line antibiotics, innovative alternative therapeutics are urgently needed. Capsule, an essential virulence determinant, is a major cause of the enhanced pathogenicity of hvKP and represents an attractive drug target to prevent the devastating clinical outcomes caused by hvKP infection. Here, we identified isoferulic acid (IFA), a natural phenolic acid compound widely present in traditional herbal medicines, as a potent broad-spectrum K. pneumoniae capsule inhibitor that suppresses capsule polysaccharide synthesis by increasing the energy status of bacteria. In this way, IFA remarkably reduced capsule thickness and impaired hypercapsule-associated hypermucoviscosity phenotype (HMV), thereby significantly sensitizing hvKP to complement-mediated bacterial killing and accelerating host cell adhesion and phagocytosis. Consequently, IFA facilitated effective bacterial clearance and thus remarkably protected mice from lethal hvKP infection, as evidenced by limited bacterial dissemination and a significant improvement in survival rate. In conclusion, this work promotes the development of a capsule-targeted alternative therapeutic strategy for the use of the promising candidate IFA as an intervention to curb hvKP infection, particularly drug-resistant cases.

Intercellular signaling stabilizes single-cell level phenotypic transitions and accelerates the reestablishment of equilibrium of heterogeneous cancer cell populations.

Cancer cells within tumors exhibit a wide range of phenotypic states driven by non-genetic mechanisms in addition to extensively studied genetic alterations. Conversions among cancer cell states can result in intratumoral heterogeneity which contributes to metastasis and development of drug resistance. However, mechanisms underlying the initiation and/or maintenance of such phenotypic plasticity are poorly understood. In particular, the role of intercellular communications in phenotypic plasticity remains elusive. In this study, we employ a multiscale inference-based approach using single-cell RNA sequencing (scRNA-seq) data to explore how intercellular interactions influence phenotypic dynamics of cancer cells, particularly cancers undergoing epithelial-mesenchymal transition. Our inference approach reveals that signaling interactions between cancerous cells in small cell lung cancer (SCLC) result in seemingly contradictory behaviors, reinforcing the cellular phenotypes and maintaining population-level intratumoral heterogeneity. Additionally, we find a recurring signaling pattern across multiple types of cancer in which the mesenchymal-like subtypes utilize signals from other subtypes to reinforce its phenotype, further promoting the intratumoral heterogeneity. We use a mathematical model based on ordinary differential equations to show that inter-subtype communication accelerates the development of heterogeneous tumor populations. Our work highlights the critical role of intercellular signaling in sustaining intratumoral heterogeneity, and our approach of computational analysis of scRNA-seq data can infer inter- and intra-cellular signaling networks in a holistic manner.

Lanosterol 14α-Demethylase (CYP51)/Heat Shock Protein 90 (Hsp90) Dual Inhibitors for the Treatment of Invasive Candidiasis.

Invasive candidiasis has attracted global attention with a high incidence and mortality. Current antifungal drugs are limited by unfavorable therapeutic efficacy, significant hepatorenal toxicity, and the development of drug resistance. Herein, we designed the first generation of lanosterol 14α-demethylase (CYP51)/heat shock protein 90 (Hsp90) dual inhibitors on the basis of antifungal synergism. Among them, dual inhibitor MM4 exhibited potent in vitro and in vivo antifungal activity against Candida albicans and effectively inhibited important fungal virulence factors (e.g., hyphae, biofilm). Therefore, CYP51/Hsp90 dual inhibitors show great promise in the development of novel antifungal drugs to combat invasive candidiasis.

Structural and Functional Studies on HIV Protease: Mechanism of Action, Subtypes, Inhibitors, and Drug Resistance.

Human immunodeficiency virus (HIV) targets the host immune system causing acquired immunodeficiency syndrome (AIDS). Although significant advancements have been made on investigating HIV and related infections, eradicating the virus from the host immune system is still challenging. Nevertheless, the combination therapies using drugs targeting different stages in the viral life cycle are used for treatment in which HIV protease plays a vital role. Hence, it is essential to understand the structure and function of HIV protease. This review focuses on these aspects from different perspectives such as catalytic mechanism, subtypes and role of flaps in drug binding. Further, we highlight the factors affecting drug binding, evolution of drug resistance, and inhibitors reported in the literature using 3D QSAR studies.

Insights into the Emerging Therapeutic Targets of Triple-negative Breast Cancer.

Triple-negative Breast Cancer (TNBC), the most aggressive breast cancer subtype, is characterized by the non-appearance of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Clinically, TNBC is marked by its low survival rate, poor therapeutic outcomes, high aggressiveness, and lack of targeted therapies. Over the past few decades, many clinical trials have been ongoing for targeted therapies in TNBC. Although some classes, such as Poly (ADP Ribose) Polymerase (PARP) inhibitors and immunotherapies, have shown positive therapeutic outcomes, however, clinical effects are not much satisfiable. Moreover, the development of drug resistance is the major pattern observed in many targeted monotherapies. The heterogeneity of TNBC might be the cause for limited clinical benefits. Hence,, there is a need for the potential identification of new therapeutic targets to address the above limitations. In this context, some novel targets that can address the above-mentioned concerns are emerging in the era of TNBC therapy, which include Hypoxia Inducible Factor (HIF-1α), Matrix Metalloproteinase 9 (MMP-9), Tumour Necrosis Factor-α (TNF-α), β-Adrenergic Receptor (β-AR), Voltage Gated Sodium Channels (VGSCs), and Cell Cycle Regulators. Currently, we summarize the ongoing clinical trials and discuss the novel therapeutic targets in the management of TNBC.

Indirect targeting of MYC and direct targeting in combination with chemotherapies are more effective than direct mono-targeting in triple negative breast cancer

MYC amplification is disproportionally elevated in triple-negative breast cancer (TNBC) compared to other subtypes of breast cancer. Indeed, MYC has long been considered an undruggable oncogene using conventional drug design strategies or small molecules. We hypothesized that targeting MYC using asymmetric siRNA (asiRNA) alone or in combination with chemotherapeutic agents or indirectly via BRD4 and RRM2, may curb its oncogenic behavior. We developed paclitaxel-, doxorubicin-, and cisplatin-resistant MDA-MB-231 cells to study MYC's role in upregulating DNA repair genes during drug resistance development. Our results showed that the knockdown of either MYC or RRM2 downregulated both RAD51 and PARP1 but increased γH2AX. The cytotoxic effect of RRM2 knockdown was significantly (p < 0.05) higher than that of direct MYC knockdown. The knockdown of BRD4 was more effective than the direct knockdown of MYC in downregulating MYC protein. The combined use of asiRNA-VP (Vinylphosphonate) with dacomitinib or talazoparib was synthetic lethal in TNBC cell lines. Compared to chemotherapy-sensitive cells, resistant cells showed overexpression of MYC, RRM2, RAD51, and PARP1 proteins upon chemotherapy treatment, but downregulated in cells treated with asiRNA-VP combination. We confirmed that MYC knockdown upregulated cFLIP, BCL2, STAT1, pSTAT1, STAT2, and cleaved saspase-3 in both TNBC and non-small cell lung cancer (NSCLC) cell lines. Finally, we recommend a combination treatment approach that synergizes with MYC inhibition rather than monotherapy or indirect targeting via upstream regulators such as the BRD4 and RRM2 genes or selective modulation at the protein level to suppress anti-apoptotic genes (cFLIP and BCL2) at the same time.

Advances and challenges in precision imaging.

Technological innovations in genomics and related fields have facilitated large sequencing efforts, supported new biological discoveries in cancer, and spawned an era of liquid biopsy biomarkers. Despite these advances, precision oncology has practical constraints, partly related to cancer's biological diversity and spatial and temporal complexity. Advanced imaging technologies are being developed to address some of the current limitations in early detection, treatment selection and planning, drug delivery, and therapeutic response, as well as difficulties posed by drug resistance, drug toxicity, disease monitoring, and metastatic evolution. We discuss key areas of advanced imaging for improving cancer outcomes and survival. Finally, we discuss practical challenges to the broader adoption of precision imaging in the clinic and the need for a robust translational infrastructure.