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.

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.

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.

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.

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.

Time-Dependent Effects of Clinical Interventions on SARS-CoV-2 Immunity in Patients with Lung Cancer.

In patients with lung cancer (LC), understanding factors that impact the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike antibody (SAb) titers over time is critical, but challenging, due to evolving treatments, infections, vaccinations, and health status. The objective was to develop a time-dependent regression model elucidating individual contributions of factors influencing SAb levels in LC patients using a prospective, longitudinal, multi-institutional cohort study initiated in January 2021. The study evaluated 296 LC patients-median age 69; 55% female; 50% stage IV. Blood samples were collected every three months to measure SAb levels using FDA-approved ELISA. Asymptomatic and unreported infections were documented through measurement of anti-nucleocapsid Ab levels (Meso Scale Discovery). Associations between clinical characteristics and titers were evaluated using a time-dependent linear regression model with a generalized estimating equation (GEE), considering time-independent variables (age, sex, ethnicity, smoking history, histology, and stage) and time-dependent variables (booster vaccinations, SARS-CoV-2 infections, cancer treatment, steroid use, and influenza vaccination). Significant time-dependent effects increasing titer levels were observed for prior SARS-CoV-2 infection (p < 0.001) and vaccination/boosters (p < 0.001). Steroid use (p = 0.043) and chemotherapy (p = 0.033) reduced titer levels. Influenza vaccination was associated with increased SAb levels (p < 0.001), independent of SARS-CoV-2 vaccine boosters. Prior smoking significantly decreased titers in females (p = 0.001). Age showed no association with titers. This GEE-based linear regression model unveiled the nuanced impact of multiple variables on patient anti-spike Ab levels over time. After controlling for the major influences of vaccine and SARS-CoV-2 infections, chemotherapy and steroid use were found to have negatively affected titers. Smoking in females significantly decreased titers. Surprisingly, influenza vaccinations were also significantly associated, likely indirectly, with improved SARS-CoV-2 titers.

Soluble immune checkpoints: implications for cancer prognosis and response to immune checkpoint therapy and conventional therapies.

Longitudinal sampling of tumor tissue from patients with solid cancers, aside from melanoma and a few other cases, is often unfeasible, and thus may not capture the plasticity of interactions between the tumor and immune system under selective pressure of a given therapy. Peripheral blood analyses provide salient information about the human peripheral immunome while offering technical and practical advantages over traditional tumor biopsies, and should be utilized where possible alongside interrogation of the tumor. Some common blood-based biomarkers used to study the immune response include immune cell subsets, circulating tumor DNA, and protein analytes such as cytokines. With the recent explosion of immune checkpoint inhibitors (ICI) as a modality of treatment in multiple cancer types, soluble immune checkpoints have become a relevant area of investigation for peripheral immune-based biomarkers. However, the exact functions of soluble immune checkpoints and their roles in cancer for the most part remain unclear. This review discusses current literature on the production, function, and expression of nine soluble immune checkpoints - sPD-L1, sPD-1, sCTLA4, sCD80, sTIM3, sLAG3, sB7-H3, sBTLA, and sHVEM - in patients with solid tumors, and explores their role as biomarkers of response to ICI as well as to conventional therapies (chemotherapy, radiotherapy, targeted therapy, and surgery) in cancer patients.

The role of HOTAIR in the modulation of resistance to anticancer therapy.

Leading anti-tumour therapeutic strategies typically involve surgery and radiotherapy for locally advanced (non-metastatic) cancers, while hormone therapy, chemotherapy, and molecular targeted therapy are the current treatment options for metastatic cancer. Despite the initially high sensitivity rate to anticancer therapies, a large number of patients develop resistance, leading to a poor prognosis. The mechanisms related to drug resistance are highly complex, and long non-coding RNAs appear to play a crucial role in these processes. Among these, the lncRNA homeobox transcript antisense intergenic RNA (HOTAIR), widely implicated in cancer initiation and progression, likewise plays a significant role in anticancer drug resistance. It can modulate cell activities such as proliferation, apoptosis, hypoxia, autophagy, as well as epithelial-mesenchymal transition, thereby contributing to the development of resistant tumour cells. In this manuscript, we describe different mechanisms of antitumor drug resistance in which HOTAIR is involved and suggest its potential as a therapeutic predictive biomarker for the management of cancer patients.

Skin Malignancies Due to Anti-Cancer Therapies.

Skin cancers involve a significant concern in cancer therapy due to their association with various treatment modalities. This comprehensive review explores the increased risk of skin cancers linked to different anti-cancer treatments, including classic immunosuppressants such as methotrexate (MTX), chemotherapeutic agents such as fludarabine and hydroxyurea (HU), targeted therapies like ibrutinib and Janus Kinase inhibitors (JAKi), mitogen-activated protein kinase pathway (MAPKP) inhibitors, sonic hedgehog pathway (SHHP) inhibitors, and radiotherapy. MTX, a widely used immunosuppressant in different fields, is associated with basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and cutaneous melanoma (CM), particularly at higher dosages. Fludarabine, HU, and other chemotherapeutic agents increase the risk of non-melanoma skin cancers (NMSCs), including cSCC and BCC. Targeted therapies like ibrutinib and JAKi have been linked to an elevated incidence of NMSCs and CM. MAPKP inhibitors, particularly BRAF inhibitors like vemurafenib, are associated with the development of cSCCs and second primary melanomas (SPMs). SHHP inhibitors like vismodegib have been linked to the emergence of cSCCs following treatment for BCC. Additionally, radiotherapy carries carcinogenic risks, especially for BCCs, with increased risks, especially with younger age at the moment of exposure. Understanding these risks and implementing appropriate screening is crucial for effectively managing patients undergoing anti-cancer therapies.

Targeting PI3K/AKT/mTOR signaling to overcome drug resistance in cancer.

This review comprehensively explores the challenge of drug resistance in cancer by focusing on the pivotal PI3K/AKT/mTOR pathway, elucidating its role in oncogenesis and resistance mechanisms across various cancer types. It meticulously examines the diverse mechanisms underlying resistance, including genetic mutations, feedback loops, and microenvironmental factors, while also discussing the associated resistance patterns. Evaluating current therapeutic strategies targeting this pathway, the article highlights the hurdles encountered in drug development and clinical trials. Innovative approaches to overcome resistance, such as combination therapies and precision medicine, are critically analyzed, alongside discussions on emerging therapies like immunotherapy and molecularly targeted agents. Overall, this comprehensive review not only sheds light on the complexities of resistance in cancer but also provides a roadmap for advancing cancer treatment.

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.

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.

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.

Liposomal Phenylephrine Nanoparticles Enhance the Antitumor Activity of Intratumoral Chemotherapy in a Preclinical Model of Melanoma.

Intratumoral injection of anticancer agents has limited efficacy and is not routinely used for most cancers. In this study, we aimed to improve the efficacy of intratumoral chemotherapy using a novel approach comprising peri-tumoral injection of sustained-release liposomal nanoparticles containing phenylephrine, which is a potent vasoconstrictor. Using a preclinical model of melanoma, we have previously shown that systemically administered (intravenous) phenylephrine could transiently shunt blood flow to the tumor at the time of drug delivery, which in turn improved antitumor responses. This approach was called dynamic control of tumor-associated vessels. Herein, we used liposomal phenylephrine nanoparticles as a "local" dynamic control strategy for the B16 melanoma. Local dynamic control was shown to increase the retention and exposure time of tumors to intratumorally injected chemotherapy (melphalan). C57BL/6 mice bearing B16 tumors were treated with intratumoral melphalan and peri-tumoral injection of sustained-release liposomal phenylephrine nanoparticles (i.e., the local dynamic control protocol). These mice had statistically significantly improved antitumor responses compared to melphalan alone (p = 0.0011), whereby 58.3% obtained long-term complete clinical response. Our novel approach of local dynamic control demonstrated significantly enhanced antitumor efficacy and is the subject of future clinical trials being designed by our group.

Hydrogen-bonded cytosine-endowed supramolecular polymeric nanogels: Highly efficient cancer cell targeting and enhanced therapeutic efficacy.

We demonstrate that cytosine moieties within physically cross-linked supramolecular polymers not only manipulate drug delivery and release, but also confer specific targeting of cancer cells to effectively enhance the safety and efficacy of chemotherapy-and thus hold significant potential as a new perspective for development of drug delivery systems. Herein, we successfully developed physically cross-linked supramolecular polymers (PECH-PEG-Cy) comprised of hydrogen-bonding cytosine pendant groups, hydrophilic poly(ethylene glycol) side chains, and a hydrophobic poly(epichlorohydrin) main chain. The polymers spontaneously self-assemble into a reversibly hydrogen-bonded network structure induced by cytosine and directly form spherical nanogels in aqueous solution. Nanogels with a high hydrogen-bond network density (i.e., a higher content of cytosine moieties) exhibit outstanding long-term structural stability in cell culture substrates containing serum, whereas nanogels with a relatively low hydrogen-bond network density cannot preserve their structural integrity. The nanogels also exhibit numerous unique physicochemical characteristics in aqueous solution, such as a desirable spherical size, high biocompatibility with normal and cancer cells, excellent drug encapsulation capacity, and controlled pH-responsive drug release properties. More importantly, in vitro experiments conclusively indicate the drug-loaded PECH-PEG-Cy nanogels can selectively induce cancer cell-specific apoptosis and cell death via cytosine receptor-mediated endocytosis, without significantly harming normal cells. In contrast, control drug-loaded PECH-PEG nanogels, which lack cytosine moieties in their structure, can only induce cell death in cancer cells through non-specific pathways, which significantly inhibits the induction of apoptosis. This work clearly demonstrates that the cytosine moieties in PECH-PEG-Cy nanogels confer selective affinity for the surface of cancer cells, which enhances their targeted cellular uptake, cytotoxicity, and subsequent induction of programmed cell death in cancer cells.

Immunotherapy and Radiation Therapy Combinatorial Approaches in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC), a prevalent and often fatal liver cancer, presents significant treatment challenges, especially in its advanced stages. This article delves into the promising approach of combining immunotherapy, particularly immune checkpoint inhibitors, with radiation therapy, a cornerstone of HCC management. Our review synthesizes current preclinical and clinical research, highlighting the potential synergistic effects of this combinational treatment. Emerging evidence suggests that this synergy enhances tumor control and improves patient survival rates. The combination leverages the localized, tumor-targeting ability of radiation therapy and the systemic, immune-boosting effects of immunotherapy, potentially overcoming the limitations inherent in each treatment modality when used separately. This integrative approach is especially promising in addressing the complex tumor microenvironment of HCC. However, the treatment landscape is nuanced, with challenges such as patient-specific response variability and potential resistance to therapies. Future research directions should focus on refining these combination strategies, tailoring them to individual patient profiles, and understanding the underlying mechanisms that govern the interaction between immunotherapy and radiation therapy. Such advancements could significantly improve HCC management, setting new standards for patient care and treatment efficacy.

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.

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.