Cell plasticity modulation by flavonoids in resistant breast carcinoma targeting the nuclear factor kappa B signaling.

Cancer cell plasticity plays a crucial role in tumor initiation, progression, and metastasis and is implicated in the multiple cancer defense mechanisms associated with therapy resistance and therapy evasion. Cancer resistance represents one of the significant obstacles in the clinical management of cancer. Some reversal chemosensitizing agents have been developed to resolve this serious clinical problem, but they have not yet been proven applicable in oncological practice. Activated nuclear factor kappa B (NF-κB) is a frequently observed biomarker in chemoresistant breast cancer (BC). Therefore, it denotes an attractive cellular target to mitigate cancer resistance. We summarize that flavonoids represent an essential class of phytochemicals that act as significant regulators of NF-κB signaling and negatively affect the fundamental cellular processes contributing to acquired cell plasticity and drug resistance. In this regard, flavokawain A, icariin, alpinetin, genistein, wogonin, apigenin, oroxylin A, xanthohumol, EGCG, hesperidin, naringenin, orientin, luteolin, delphinidin, fisetin, norwogonin, curcumin, cardamonin, methyl gallate and catechin-3-O-gallate, ampelopsin, puerarin, hyperoside, baicalein, paratocarpin E, and kaempferol and also synthetic flavonoids such as LFG-500 and 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone have been reported to specifically interfere with the NF-κB pathway with complex signaling consequences in BC cells and could be potentially crucial in re-sensitizing unresponsive BC cases. The targeting NF-κB by above-mentioned flavonoids includes the modification of tumor microenvironment and epithelial-mesenchymal transition, growth factor receptor regulations, and modulations of specific pathways such as PI3K/AKT, MAP kinase/ERK, and Janus kinase/signal transduction in BC cells. Besides that, NF-κB signaling in BC cells modulated by flavonoids has also involved the regulation of ATP-binding cassette transporters, apoptosis, autophagy, cell cycle, and changes in the activity of cancer stem cells, oncogenes, or controlling of gene repair. The evaluation of conventional therapies in combination with plasticity-regulating/sensitizing agents offers new opportunities to make significant progress towards a complete cure for cancer.

Representation of women in clinical trials supporting FDA-approval of contemporary cancer therapies.

Contemporary anticancer therapies frequently have different efficacy and side effects in men and women. Yet, whether women are well-represented in pivotal trials supporting contemporary anticancer drugs is unknown. Leveraging the Drugs@FDA database, clinicaltrials.gov, MEDLINE, and publicly available FDA-drug-reviews, we identified all pivotal (phase II and III) non-sex specific trials supporting FDA-approval of anticancer drugs (1998-2018). Observed-enrollment-rates were compared to expected-population-rates derived from concurrent US-National-Cancer-Institute's Surveillance-Epidemiology-and-End-Results (SEER) reported rates and US-Census databases. Primary outcome was the proportional representation of women across trials, evaluated by a participation-to-prevalence ratio (PPR), according to cancer type. Secondary outcome was the report of any sex-specific analysis of efficacy and/or safety, irrespective of treatment-arm. Overall, there were 148 trials, enrolling 60,216 participants (60.5 ± 4.0 years, 40.7% female, 79.1% biologic, targeted, or immune-based therapies) evaluating 99 drugs. Sex was reported in 146 (98.6%) trials, wherein 40.7% (24,538) were women, compared to 59.3% (35,678) men (p < .01). Altogether, women were under-represented in 66.9% trials compared to the proportional incidence of cancers by respective disease type; weight-average PPR of 0.91 (relative difference: -9.1%, p < .01). Women were most under-represented in gastric (PPR = 0.63), liver (PPR = 0.71), and lung (PPR = .81) cancer trials. Sex-based safety data was reported in 4.0% trials. There was no association between adequate female enrollment and drug efficacy (HR: 0.616 vs. 0.613, p = .96). Over time, there was no difference in the percentage of women recruited into clinical trials. Among pivotal clinical trials supporting contemporary FDA-approved cancer drugs, women were frequently under-represented and sex-specific-efficacy and safety-outcomes were commonly not reported.

FSP1-mediated ferroptosis in cancer: from mechanisms to therapeutic applications.

Ferroptosis is a new discovered regulated cell death triggered by the ferrous ion (Fe2+)-dependent accumulation of lipid peroxides associated with cancer and many other diseases. The mechanism of ferroptosis includes oxidation systems (such as enzymatic oxidation and free radical oxidation) and antioxidant systems (such as GSH/GPX4, CoQ10/FSP1, BH4/GCH1 and VKORC1L1/VK). Among them, ferroptosis suppressor protein 1 (FSP1), as a crucial regulatory factor in the antioxidant system, has shown a crucial role in ferroptosis. FSP1 has been well validated to ferroptosis in three ways, and a variety of intracellular factors and drug molecules can alleviate ferroptosis via FSP1, which has been demonstrated to alter the sensitivity and effectiveness of cancer therapies, including chemotherapy, radiotherapy, targeted therapy and immunotherapy. This review aims to provide important frameworks that, bring the regulation of FSP1 mediated ferroptosis into cancer therapies on the basis of existing studies.

Discovery of telomerase inhibitors: existing strategies and emerging innovations.

Telomerase, crucial for maintaining telomere length, is an attractive target for cancer therapy due to its role in cellular immortality. Despite three decades of research efforts, no small-molecule telomerase inhibitors have been clinically approved, highlighting the extensive challenges in developing effective telomerase-based therapeutics. This review examines conventional and emerging methods to measure telomerase activity and discusses existing inhibitors, including oligonucleotides and small molecules. Furthermore, this review highlights recent breakthroughs in structural studies of telomerase using cryo-electron microscopy, which can facilitate improved structure-based drug design. Altogether, advancements in structural methodologies and high-throughput screening offer promising prospects for telomerase-based cancer therapeutic development.

Safe and supportive prescribing in transgender and non-binary patients with cancer.

Global prevalence rates for transgender individuals vary with estimates ranging from 0.3% to 1%, translating to a potential global population of 24.3 million to 81 million. It is estimated that one in two people will develop cancer in their lifetime. Gender-affirming hormone therapy (GAHT) is a common medical intervention for transgender and non-binary individuals. GAHT requires careful consideration for concurrent medical care due to potential drug interactions and physiological changes. A multi-disciplinary team with expertise in transgender health, oncology and pharmacy met to develop a document summarizing current knowledge on the topic for practical use. The team included trans and non-binary authors who shaped the document's language and focus. The document gives a status update on the current understanding of GAHT and how this may intersect with the safe prescribing of systemic anti-cancer therapies (SACT). The document underwent multiple review stages including internal review, review by the British Oncology Pharmacy Association (BOPA) EDI Subcommittee and, finally, BOPA Executive Committee review and final approval. Key recommendations of this document include the use of inclusive and effective communication, vigilant monitoring of kidney function and cardiovascular health, and considerations for hormone receptor-positive cancers. The document also recognizes the multidisciplinary nature of transgender healthcare and where this relates to social prescribing.

Necessity and influencing factors for integrating oral health in cancer care for older people: a narrative review.

PURPOSE: The number of older people with poor oral health diagnosed with cancer is increasing rapidly. However, integration of oral health in cancer care for older people to prevent or minimize oral health complications of cancer treatments is uncommon, except in head and neck oncology. The aim of this review is to describe the need, role of, and factors influencing the integration of oral health(care) into the treatment of older people with cancer. METHODS: MEDLINE, CINAHL, PubMed, Scopus, and Web of Science databases were searched for papers published in the last 10 years that focus on oral health in older people diagnosed with cancer, the impact of oral health on cancer therapy, and integrated oral health in cancer treatment. RESULTS: From 523 related papers, 68 publications were included and summarized as follows: (1) oral complications associated with cancer therapies, (2) the need for oral healthcare in older people with cancer, (3) the role of integration of oral health in cancer care, and (4) influencing factors such as ageism, interprofessional education and collaborations, oral healthcare workforce, oral health literacy, and financial considerations. CONCLUSION: Integration of oral healthcare is highly recommended for the overall well-being of older people with cancer to prevent, minimize, and manage complications in cancer treatment. However, oral healthcare has not been integrated in cancer care yet, except for head and neck cancers. This review identified a notable gap in the literature, highlighting the need for research on integration of oral healthcare in geriatric oncology.

Targeted ferritinophagy in gastrointestinal cancer: from molecular mechanisms to implications.

Gastrointestinal cancer is a significant global health burden, necessitating the development of novel therapeutic strategies. Emerging evidence has highlighted the potential of targeting ferritinophagy as a promising approach for the treatment of gastrointestinal cancer. Ferritinophagy is a form of selective autophagy that is mediated by the nuclear receptor coactivator 4 (NCOA4). This process plays a crucial role in regulating cellular iron homeostasis and has been implicated in various pathological conditions, including cancer. This review discusses the molecular mechanisms underlying ferritinophagy and its relevance to gastrointestinal cancer. Furthermore, we highlight the potential therapeutic implications of targeting ferritinophagy in gastrointestinal cancer. Several approaches have been proposed to modulate ferritinophagy, including small molecule inhibitors and immunotherapeutic strategies. We discuss the advantages and challenges associated with these therapeutic interventions and provide insights into their potential clinical applications.

Drug-Resistant Epithelial Ovarian Cancer: Current and Future Perspectives.

Epithelial ovarian cancer (EOC) is a complex disease with diverse histological subtypes, which, based on the aggressiveness and course of disease progression, have recently been broadly grouped into type I (low-grade serous, endometrioid, clear cell, and mucinous) and type II (high-grade serous, high-grade endometrioid, and undifferentiated carcinomas) categories. Despite substantial differences in pathogenesis, genetics, prognosis, and treatment response, clinical diagnosis and management of EOC remain similar across the subtypes. Debulking surgery combined with platinum-taxol-based chemotherapy serves as the initial treatment for High Grade Serous Ovarian Carcinoma (HGSOC), the most prevalent one, and for other subtypes, but most patients exhibit intrinsic or acquired resistance and recur in short duration. Targeted therapies, such as anti-angiogenics (e.g., bevacizumab) and PARP inhibitors (for BRCA-mutated cancers), offer some success, but therapy resistance, through various mechanisms, poses a significant challenge. This comprehensive chapter delves into emerging strategies to address these challenges, highlighting factors like aberrant miRNAs, metabolism, apoptosis evasion, cancer stem cells, and autophagy, which play pivotal roles in mediating resistance and disease relapse in EOC. Beyond standard treatments, the focus of this study extends to alternate targeted agents, including immunotherapies like checkpoint inhibitors, CAR T cells, and vaccines, as well as inhibitors targeting key oncogenic pathways in EOC. Additionally, this chapter covers disease classification, diagnosis, resistance pathways, standard treatments, and clinical data on various emerging approaches, and advocates for a nuanced and personalized approach tailored to individual subtypes and resistance mechanisms, aiming to enhance therapeutic outcomes across the spectrum of EOC subtypes.

Microbial Therapy and Breast Cancer Management: Exploring Mechanisms, Clinical Efficacy, and Integration within the One Health Approach.

This comprehensive review elucidates the profound relationship between the human microbiome and breast cancer management. Recent findings highlight the significance of microbial alterations in tissue, such as the gut and the breast, and their role in influencing the breast cancer risk, development, progression, and treatment outcomes. We delve into how the gut microbiome can modulate systemic inflammatory responses and estrogen levels, thereby impacting cancer initiation and therapeutic drug efficacy. Furthermore, we explore the unique microbial diversity within breast tissue, indicating potential imbalances brought about by cancer and highlighting specific microbes as promising therapeutic targets. Emphasizing a holistic One Health approach, this review underscores the importance of integrating insights from human, animal, and environmental health to gain a deeper understanding of the complex microbe-cancer interplay. As the field advances, the strategic manipulation of the microbiome and its metabolites presents innovative prospects for the enhancement of cancer diagnostics and therapeutics. However, rigorous clinical trials remain essential to confirm the potential of microbiota-based interventions in breast cancer management.

Advances in Medicine: Photodynamic Therapy.

Over the past decades, medicine has made enormous progress, revolutionized by modern technologies and innovative therapeutic approaches. One of the most exciting branches of these developments is photodynamic therapy (PDT). Using a combination of light of a specific wavelength and specially designed photosensitizing substances, PDT offers new perspectives in the fight against cancer, bacterial infections, and other diseases that are resistant to traditional treatment methods. In today's world, where there is a growing problem of drug resistance, the search for alternative therapies is becoming more and more urgent. Imagine that we could destroy cancer cells or bacteria using light, without the need to use strong chemicals or antibiotics. This is what PDT promises. By activating photosensitizers using appropriately adjusted light, this therapy can induce the death of cancer or bacterial cells while minimizing damage to surrounding healthy tissues. In this work, we will explore this fascinating method, discovering its mechanisms of action, clinical applications, and development prospects. We will also analyze the latest research and patient testimonies to understand the potential of PDT for the future of medicine.

Microbe-based therapies for colorectal cancer: Advantages and limitations.

Cancer is one of the leading global causes of death in both men and women. Colorectal cancer (CRC) alone accounts for ∼10 % of total new global cases and poses an over 4% lifetime risk of developing cancer. Recent advancements in the field of biotechnology and microbiology concocted novel microbe-based therapies to treat various cancers, including CRC. Microbes have been explored for human use since centuries, especially for the treatment of various ailments. The utility of microbes in cancer therapeutics is widely explored, and various bacteria, fungi, and viruses are currently in use for the development of cancer therapeutics. The human gut hosts about 100 trillion microbes that release their metabolites in active, inactive, or dead conditions. Microbial secondary metabolites, proteins, immunotoxins, and enzymes are used to target cancer cells to induce cell cycle arrest, apoptosis, and death. Various approaches, such as dietary interventions, the use of prebiotics and probiotics, and fecal microbiota transplantation have been used to modulate the gut microbiota in order to prevent or treat CRC pathogenesis. The present review highlights the role of the gut microbiota in CRC precipitation, the potential mechanisms and use of microorganisms as CRC biomarkers, and strategies to modulate microbiota for the prevention and treatment of CRC.

Oncolytic Virus-Driven Biotherapies from Bench to Bedside.

With advances in cancer biology and an ever-deepening understanding of molecular virology, oncolytic virus (OV)-driven therapies have developed rapidly and become a promising alternative to traditional cancer therapies. In recent years, satisfactory results for oncolytic virus therapy (OVT) are achieved at both the cellular and organismal levels, and efforts are being increasingly directed toward clinical trials. Unfortunately, OVT remains ineffective in these trials, especially when performed using only a single OV reagent. In contrast, integrated approaches, such as using immunotherapy, chemotherapy, or radiotherapy, alongside OVT have demonstrated considerable efficacy. The challenges of OVT in clinical efficacy include the restricted scope of intratumoral injections and poor targeting of intravenous administration. Further optimization of OVT delivery is needed before OVs become a viable therapy for tumor treatment. In this review, the development process and antitumor mechanisms of OVs are introduced. The advances in OVT delivery routes to provide perspectives and directions for the improvement of OVT delivery are highlighted. This review also discusses the advantages and limitations of OVT monotherapy and combination therapy through the lens of recent clinical trials and aims to chart a course toward safer and more effective OVT strategies.

Association between the antioxidant properties of SESN proteins and anti-cancer therapies.

Since the beginning of SESN protein development, they have attracted highly progressive attention due to their regulatory role in multiple signalling pathways. Through their antioxidant activity and autophagy regulation implication, they can function as powerful antioxidants to reduce oxidative stress in cells. SESN proteins received special attention in the field of regulation of reactive oxygen species level in the cell and its interplay with signalling pathways determining energy and nutrient homeostasis. Since perturbations in these pathways are implicated in cancer onset and development, SESNs might constitute potential novel therapeutic targets of broad interest. In this review, we discuss the impact of SESN proteins on anti-cancer therapy based on naturally occurring compounds and conventionally used drugs that influence oxidative stress and autophagy-induced cellular signalling pathways. The significant changes in reactive oxygen species level and nutrient status in cancer cells generate subsequent biological effect through the regulation of SESN-dependent pathways. Thus, SESN may serve as the key molecule for regulating anti-cancer drugs' induced cellular response.

Cancer drugs with high repositioning potential for Alzheimer's disease.

INTRODUCTION: Despite the recent full FDA approval of lecanemab, there is currently no disease modifying therapy (DMT) that can efficiently slow down the progression of Alzheimer's disease (AD) in the general population. This statement emphasizes the need to identify novel DMTs in the shortest time possible to prevent a global epidemic of AD cases as the world population experiences an increase in lifespan. AREAS COVERED: Here, we review several classes of anti-cancer drugs that have been or are being investigated in Phase II/III clinical trials for AD, including immunomodulatory drugs, RXR agonists, sex hormone therapies, tyrosine kinase inhibitors, and monoclonal antibodies. EXPERT OPINION: Given the overall course of brain pathologies during the progression of AD, we express a great enthusiasm for the repositioning of anti-cancer drugs as possible AD DMTs. We anticipate an increasing number of combinatorial therapy strategies to tackle AD symptoms and their underlying pathologies. However, we strongly encourage improvements in clinical trial study designs to better assess target engagement and possible efficacy over sufficient periods of drug exposure.

Medicinal Mushroom Supplements in Cancer: A Systematic Review of Clinical Studies.

PURPOSE OF REVIEW: Patients seek clinical guidance on mushroom supplements that can be given alongside conventional treatments, but most research on such fungi has been preclinical. The current systematic review focused on clinical studies of mushrooms in cancer care conducted in the past 10 years. We searched Medline (Ovid), Embase (Ovid), Scopus (Wiley), and Cochrane Library to identify all mushroom studies conducted in humans published from January 2010 through December 2020. Two authors independently assessed papers for inclusion. RECENT FINDINGS: Of 136 clinical studies identified by screening 2349, 39 met inclusion criteria. The studies included 12 different mushroom preparations. A survival benefit was reported using Huaier granules (Trametes robiniophila Murr) in 2 hepatocellular carcinoma studies and 1 breast cancer study. A survival benefit was also found in 4 gastric cancer studies using polysaccharide-K (polysaccharide-Kureha; PSK) in the adjuvant setting. Eleven studies reported a positive immunological response. Quality-of-life (QoL) improvement and/or reduced symptom burden was reported in 14 studies using various mushroom supplements. Most studies reported adverse effects of grade 2 or lower, mainly nausea, vomiting, diarrhea, and muscle pain. Limitations included small sample size and not using randomized controlled trial design. Many of the reviewed studies were small and observational. Most showed favorable effects of mushroom supplements in reducing the toxicity of chemotherapy, improving QoL, favorable cytokine response, and possibly better clinical outcomes. Nevertheless, the evidence is inconclusive to recommend the routine use of mushrooms for cancer patients. More trials are needed to explore mushroom use during and after cancer treatment.

Effects of Nanosecond Pulsed Electric Field (nsPEF) on a Multicellular Spheroid Tumor Model: Influence of Pulse Duration, Pulse Repetition Rate, Absorbed Energy, and Temperature.

Cellular response upon nsPEF exposure depends on different parameters, such as pulse number and duration, the intensity of the electric field, pulse repetition rate (PRR), pulsing buffer composition, absorbed energy, and local temperature increase. Therefore, a deep insight into the impact of such parameters on cellular response is paramount to adaptively optimize nsPEF treatment. Herein, we examined the effects of nsPEF ≤ 10 ns on long-term cellular viability and growth as a function of pulse duration (2-10 ns), PRR (20 and 200 Hz), cumulative time duration (1-5 µs), and absorbed electrical energy density (up to 81 mJ/mm3 in sucrose-containing low-conductivity buffer and up to 700 mJ/mm3 in high-conductivity HBSS buffer). Our results show that the effectiveness of nsPEFs in ablating 3D-grown cancer cells depends on the medium to which the cells are exposed and the PRR. When a medium with low-conductivity is used, the pulses do not result in cell ablation. Conversely, when the same pulse parameters are applied in a high-conductivity HBSS buffer and high PRRs are applied, the local temperature rises and yields either cell sensitization to nsPEFs or thermal damage.

Repurposing old drugs as new inhibitors of the ubiquitin-proteasome pathway for cancer treatment.

The ubiquitin-proteasome system (UPS) plays a central role in the degradation of cellular proteins. Targeting protein degradation has been validated as an effective strategy for cancer therapy since 2003. Several components of the UPS have been validated as potential anticancer targets, including 20S proteasomes, 19S proteasome-associated deubiquitinases (DUBs) and ubiquitin ligases (E3s). 20S proteasome inhibitors (such as bortezomib/BTZ and carfilzomib/CFZ) have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of multiple myeloma (MM) and some other liquid tumors. Although survival of MM patients has been improved by the introduction of BTZ-based therapies, these clinical 20S proteasome inhibitors have several limitations, including emergence of resistance in MM patients, neuro-toxicities, and little efficacy in solid tumors. One of strategies to improve the current status of cancer treatment is to repurpose old drugs with UPS-inhibitory properties as new anticancer agents. Old drug reposition represents an attractive drug discovery approach compared to the traditional de novo drug discovery process which is time-consuming and costly. In this review, we summarize status of repurposed inhibitors of various UPS components, including 20S proteasomes, 19S-associated DUBs, and ubiquitin ligase E3s. The original and new mechanisms of action, molecular targets, and potential anticancer activities of these repurposed UPS inhibitors are reviewed, and their new uses including combinational therapies for cancer treatment are discussed.

Visualizing cancer extravasation: from mechanistic studies to drug development.

Metastasis is a multistep process that accounts for the majority of cancer-related death. By the end of metastasize dissemination, circulating tumor cells (CTC) need to extravasate the blood vessels at metastatic sites to form new colonization. Although cancer cell extravasation is a crucial step in cancer metastasis, it has not been successfully targeted by current anti-metastasis strategies due to the lack of a thorough understanding of the molecular mechanisms that regulate this process. This review focuses on recent progress in cancer extravasation visualization techniques, including the development of both in vitro and in vivo cancer extravasation models, that shed light on the underlying mechanisms. Specifically, multiple cancer extravasation stages, such as the adhesion to the endothelium and transendothelial migration, are successfully probed using these technologies. Moreover, the roles of different cell adhesive molecules, chemokines, and growth factors, as well as the mechanical factors in these stages are well illustrated. Deeper understandings of cancer extravasation mechanisms offer us new opportunities to escalate the discovery of anti-extravasation drugs and therapies and improve the prognosis of cancer patients.

Near-Infrared-II Quantum Dots for In Vivo Imaging and Cancer Therapy.

In vivo fluorescence imaging can perform real-time, noninvasive, and high spatiotemporal resolution imaging to accurately obtain the dynamic biological information in vivo, which plays significant roles in the early diagnosis and treatment of cancer. However, traditional in vivo fluorescence imaging usually operates in the visible and near-infrared (NIR)-I windows, which are severely interfered by the strong tissue absorption, tissue scattering, and autofluorescence. The emergence of NIR-II imaging at 1000-1700 nm significantly breaks through the imaging limitations in deep tissues, due to less tissue scattering and absorption. Benefiting from the outstanding optical properties of NIR-II quantum dots (QDs), such as high brightness and good photostability, in vivo fluorescence imaging exhibits excellent temporal-spatial resolution and large penetration depth, and QDs have become a kind of promising fluorescent biomarkers in the field of in vivo fluorescence imaging. Herein, the authors review NIR-II QDs from preparation to modification, and summarize recent applications of NIR-II QDs, including in vivo imaging and imaging-guided therapies. Finally, they discuss the special concerns when NIR-II QDs are shifted from in vivo imaging applications to further in-depth applications.

Assessing cognitive toxicity in early phase trials - What are we missing?

OBJECTIVES: Novel therapies, such as, small protein molecule inhibitors and immunotherapies are first tested clinically in Phase I trials. Moving on to later phase trials and ultimately standard practice. A key aim of these early clinical trials is to define a toxicity profile; however, the emphasis is often on safety. The concern is cognitive toxicity is poorly studied in this context and may be under-reported. The aim of this review is to map evidence of cognitive assessment, toxicity, and confounding factors within reports from Phase I trials and consider putative mechanisms of impairment aligned with mechanisms of novel therapies. METHODS: A scoping review methodology was applied to the search of databases, including Embase, MEDLINE, Clinicaltrials.gov. A [keyword search was conducted, results screened for duplication then inclusion/exclusion criteria applied. Articles were further screened for relevance; data organised into categories and charted in a tabular format]. Evidence was collated and summarised into a narrative synthesis. RESULTS: Despite the availability of robust ways to assess cognitive function, these are not routinely included in the conduct of early clinical trials. Reports of cognitive toxicity in early Phase I trials are limited and available evidence on this shows that a proportion of patients experience impaired cognitive function over the course of participating in a Phase I trial. Links are identified between the targeted action of some novel therapies and putative mechanisms of cognitive impairment. CONCLUSION: The review provides rationale for research investigating cognitive function in this context. A study exploring the cognitive function of patients on Phase I trials and the feasibility of formally assessing this within early clinical trials is currently underway at the Royal Marsden.