Abstract: Hyperthermia (HT) is an anti-cancer therapy commonly used with radio and chemotherapies based on applying heat (39–45 °C) to inhibit tumor growth. However, controlling heat towards tumors and not normal tissues is challenging. Therefore, nanoparticles (NPs) are used in HT to apply heat only to tumor tissues to induce DNA damage and the expression of heat shock proteins, which eventually result in apoptosis. The aim of this review article is to summarize recent advancements in HT with the use of magnetic NPs to locally increase temperature and promote cell death. In addition, the recent development of nanocarriers as NP-based drug delivery systems is discussed. Finally, the efficacy of HT combined with chemotherapy, radiotherapy, gene therapy, photothermal therapy, and immunotherapy is explored.

Abstract: Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer mortality worldwide. There are disparities in the epidemiology of CRC across different populations, most probably due to differences in exposure to lifestyle and environmental factors related to CRC. Prevention is the most effective method for controlling CRC. Primary prevention includes determining and avoiding modifiable risk factors (e.g., alcohol consumption, smoking, and dietary factors) as well as increasing protective factors (e.g., physical activity, aspirin). Further studies, especially randomized, controlled trials, are needed to clarify the association between CRC incidence and exposure to different risk factors or protective factors. Detection and removal of precancerous colorectal lesions is also an effective strategy for controlling CRC. Multiple factors, both at the individual and community levels (e.g., patient preferences, availability of screening modalities, costs, benefits, and adverse events), should be taken into account in designing and implementing CRC screening programs. Health policymakers should consider the best decision in identifying the starting age and selection of the most effective screening strategies for the target population. This review aims to present updated evidence on the epidemiology, risk factors, and prevention of CRC.

Abstract: The rise of drug resistance in cancer cells presents a formidable challenge in modern oncology, necessitating the exploration of innovative therapeutic strategies. This review investigates the latest advancements in overcoming drug resistance mechanisms employed by cancer cells, focusing on emerging therapeutic modalities. The intricate molecular insights into drug resistance, including genetic mutations, efflux pumps, altered signaling pathways, and microenvironmental influences, are discussed. Furthermore, the promising avenues offered by targeted therapies, combination treatments, immunotherapies, and precision medicine approaches are highlighted. Specifically, the synergistic effects of combining traditional cytotoxic agents with molecularly targeted inhibitors to circumvent resistance pathways are examined. Additionally, the evolving landscape of immunotherapeutic interventions, including immune checkpoint inhibitors and adoptive cell therapies, is explored in terms of bolstering anti-tumor immune responses and overcoming immune evasion mechanisms. Moreover, the significance of biomarker-driven strategies for predicting and monitoring treatment responses is underscored, thereby optimizing therapeutic outcomes. For insights into the future direction of cancer treatment paradigms, the current review focused on prevailing drug resistance challenges and improving patient outcomes, through an integrative analysis of these emerging therapeutic strategies.

Abstract: Simple Summary Although immune check point inhibitors have been established as a new paradigm in cancer treatment, they have shown no clinical benefit in immune excluded or dessert tumors. Dendritic cells promote and coordinate the immune system. Dendritic cell vaccination enriches tumor milieu and potentiates patient systemic antitumoral responses. In this work we review the strengths and weaknesses of dendritic cell vaccines in different solid tumors regarding their role to improve their clinical efficacy. To date, dendritic cell vaccines have induced immune responses in patients without a significant impact on outcome. Improvements in vaccine formulations, selection of patients and combinations with other antitumoral therapies are needed to increase patients’ survival. Abstract Cancer immunotherapy modulates the immune system, overcomes immune escape and stimulates immune defenses against tumors. Dendritic cells (DCs) are professional promoters of immune responses against tumor antigens with the outstanding ability to coordinate the innate and adaptive immune systems. Evidence suggests that there is a decrease in both the number and function of DCs in cancer patients. Therefore, they represent a strong scaffold for therapeutic interventions. DC vaccination (DCV) is safe, and the antitumoral responses induced are well established in solid tumors. Although the addition of checkpoint inhibitors (CPIs) to chemotherapy has provided new options in the treatment of cancer, they have shown no clinical benefit in immune desert tumors or in those tumors with dysfunctional or exhausted T-cells. In this way, DC-based therapy has demonstrated the ability to modify the tumor microenvironment for immune enriched tumors and to potentiate systemic host immune responses as an active approach to treating cancer patients. Application of DCV in cancer seeks to obtain long-term antitumor responses through an improved T-cell priming by enhancing previous or generating de novo immune responses. To date, DCV has induced immune responses in the peripheral blood of patients without a significant clinical impact on outcome. Thus, improvements in vaccines formulations, selection of patients based on biomarkers and combinations with other antitumoral therapies are needed to enhance patient survival. In this work, we review the role of DCV in different solid tumors with their strengths and weaknesses, and we finally mention new trends to improve the efficacy of this immune strategy.

Abstract: Simple Summary Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with global impact, especially in the context of the rising epidemic of metabolic-dysfunction-associated steatotic liver disease and alcohol-related liver disease. The treatment landscape for HCC is evolving and has changed significantly in the last few years with new treatment options for patients, while the multidisciplinary team model of care remains critical. This review aims to summarize the various treatment options for patients at all stages of HCC, highlighting the growing array of systemic therapies with multi-modal options, including the potential of combining locoregional therapies with immunotherapy across different stages of the disease. With the increasing recognition of the importance of patient-centered care, the future paradigm of HCC care includes the incorporation of non-hospice palliative care in the multidisciplinary team care model to improve patient quality of care, quality of life, and overall outcomes. Abstract Liver cancer is the third most common cause of cancer-related deaths worldwide, and hepatocellular carcinoma (HCC) makes up the majority of liver cancer cases. Despite the stabilization of incidence rates in recent years due to effective viral hepatitis treatments, as well as improved outcomes from early detection and treatment advances, the burden of HCC is anticipated to rise again due to increasing rates of metabolic dysfunction-associated steatotic liver disease and alcohol-related liver disease. The treatment landscape is evolving and requires a multidisciplinary approach, often involving multi-modal treatments that include surgical resection, transplantation, local regional therapies, and systemic treatments. The optimal approach to the care of the HCC patient requires a multidisciplinary team involving hepatology, medical oncology, diagnostic and interventional radiology, radiation oncology, and surgery. In order to determine which approach is best, an individualized treatment plan should consider the patient’s liver function, functional status, comorbidities, cancer stage, and preferences. In this review, we provide an overview of the current treatment options and key trials that have revolutionized the management of HCC. We also discuss evolving treatment paradigms for the future.

Abstract: Cancer is a life-threatening disease and one of the leading causes of death worldwide. Despite significant advancements in therapeutic options, most available anti-cancer agents have limited efficacy. In this context, natural compounds with diverse chemical structures have been investigated for their multimodal anti-cancer properties. Curcumin is a polyphenol isolated from the rhizomes of Curcuma longa and has been widely studied for its anti-inflammatory, anti-oxidant, and anti-cancer effects. Curcumin acts on the regulation of different aspects of cancer development, including initiation, metastasis, angiogenesis, and progression. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway is a key target in cancer therapy, since it is implicated in initiation, proliferation, and cancer cell survival. Curcumin has been found to inhibit the PI3K/Akt pathway in tumor cells, primarily via the regulation of different key mediators, including growth factors, protein kinases, and cytokines. This review presents the therapeutic potential of curcumin in different malignancies, such as glioblastoma, prostate and breast cancer, and head and neck cancers, through the targeting of the PI3K/Akt signaling pathway.

Abstract: Metabolic-dysfunction-associated steatotic liver disease (MASLD, previously known as non-alcoholic fatty liver disease (NAFLD)) represents a rapidly increasing cause of chronic liver disease and hepatocellular carcinoma (HCC), mirroring increasing rates of obesity and metabolic syndrome in the Western world. MASLD-HCC can develop at an earlier stage of fibrosis compared to other causes of chronic liver disease, presenting challenges in how to risk-stratify patients to set up effective screening programmes. Therapeutic decision making for MASLD-HCC is also complicated by medical comorbidities and disease presentation at a later stage. The response to treatment, particularly immune checkpoint inhibitors, may vary by the aetiology of the disease, and, in the future, patient stratification will be key to optimizing the therapeutic pathways.

Abstract: Aerobic glycolysis in cancer cells, originally observed by Warburg 100 years ago, which involves the production of lactate as the end product of glucose breakdown even in the presence of adequate oxygen, is the foundation for the current interest in the cancer-cell-specific reprograming of metabolic pathways. The renewed interest in cancer cell metabolism has now gone well beyond the original Warburg effect related to glycolysis to other metabolic pathways that include amino acid metabolism, one-carbon metabolism, the pentose phosphate pathway, nucleotide synthesis, antioxidant machinery, etc. Since glucose and amino acids constitute the primary nutrients that fuel the altered metabolic pathways in cancer cells, the transporters that mediate the transfer of these nutrients and their metabolites not only across the plasma membrane but also across the mitochondrial and lysosomal membranes have become an integral component of the expansion of the Warburg effect. In this review, we focus on the interplay between these transporters and metabolic pathways that facilitates metabolic reprogramming, which has become a hallmark of cancer cells. The beneficial outcome of this recent understanding of the unique metabolic signature surrounding the Warburg effect is the identification of novel drug targets for the development of a new generation of therapeutics to treat cancer.

Abstract: Simple Summary Cuproptosis is a recently identified form of cell death induced by imbalanced copper levels. We aimed to explore the mechanism underlying copper-induced cell death. To achieve this, we surveyed the literature to understand the biochemical implications of cuproptosis in diseases, particularly in the context of cancer. The concept of copper ionophores, such as elesclomol and disulfiram, is highlighted as they elevate intracellular copper levels, triggering oxidative stress and ultimately leading to cell death–a potential avenue for cancer therapy. Furthermore, we will delve into the intricate relationship between copper, mitochondrial respiration, and protein lipoylation, shedding light on their connections in inducing cell death. Abstract Copper, an essential element for various biological processes, demands precise regulation to avert detrimental health effects and potential cell toxicity. This paper explores the mechanisms of copper-induced cell death, known as cuproptosis, and its potential health and disease implications, including cancer therapy. Copper ionophores, such as elesclomol and disulfiram, increase intracellular copper levels. This elevation triggers oxidative stress and subsequent cell death, offering potential implications in cancer therapy. Additionally, copper ionophores disrupt mitochondrial respiration and protein lipoylation, further contributing to copper toxicity and cell death. Potential targets and biomarkers are identified, as copper can be targeted to those proteins to trigger cuproptosis. The role of copper in different cancers is discussed to understand targeted cancer therapies using copper nanomaterials, copper ionophores, and copper chelators. Furthermore, the role of copper is explored through diseases such as Wilson and Menkes disease to understand the physiological mechanisms of copper. Exploring cuproptosis presents an opportunity to improve treatments for copper-related disorders and various cancers, with the potential to bring significant advancements to modern medicine.

Abstract: Simple Summary Lichen planus (LP) is a chronic inflammatory mucocutaneous disease of autoimmune nature and unknown etiology, which can affect the oral mucosa, skin, nails, scalp, genitalia, and other mucous membranes. The anatomical location most frequently affected by LP is the oral cavity—called oral lichen planus (OLP)—where white reticular lesions may also be accompanied by erosive, atrophic, bullous, papular, or plaque lesions. The most important feature of OLP is its capacity to develop into oral cancer throughout the course of the disease, which is why OLP is currently recognized as an oral potentially malignant disorder (OPMD). New primary-level studies (n = 20; 11,512 patients suffering from OLP or related lesions) have been published in the last 5 years on this topic. In the present meta-analysis, we provide an updated OLP malignant transformation ratio, which is higher than what was previously reported; resolve some remaining controversies; and provide new recommendations for clinical practice in the management of OLP patients. Abstract A systematic review and a meta-analysis is presented on published articles on the malignant transformation of oral lichen planus (OLP) and related conditions, which, based on current evidence, updates an earlier systematic review published by our research group that included publications until November 2018. In this updated study (Nov-2023) we searched MEDLINE, Embase, Web of Science, and Scopus. We evaluated the methodological quality of studies (QUIPS tool) and carried out meta-analyses. The inclusion criteria were met by 101 studies (38,083 patients), of which, 20 new primary-level studies (11,512 patients) were published in the last 5 years and were added to our updated study. The pooled malignant transformation ratio was 1.43% (95% CI = 1.09–1.80) for OLP; 1.38% (95% CI = 0.16–3.38) for oral lichenoid lesions; 1.20% (95% CI = 0.00–4.25) for lichenoid reactions; and 5.13% (95% CI = 1.90–9.43) for OLP with dysplasia. No significant differences were found between the OLL or LR groups and the OLP subgroup (p = 0.853 and p = 0.328, respectively), and the malignant transformation was significantly higher for the OLP with dysplasia group in comparison with the OLP group (p = 0.001). The factors that had a significant impact with a higher risk of malignant transformation were the presence of epithelial dysplasia, a higher methodological quality, the consumption of tobacco and alcohol, the location of lesions on the tongue, the presence of atrophic and erosive lesions, and infection by the hepatitis C virus. In conclusion, OLP behaves as an oral potentially malignant disorder (OPMD), whose malignancy ratio is probably underestimated as a consequence essentially of the use of inadequate diagnostic criteria and the low methodological quality of the studies on the subject.

Abstract: Radiotherapy, a crucial technique in cancer therapy, has traditionally relied on the premise of largely unchanging patient anatomy during the treatment course and encompassing uncertainties by target margins. This review introduces adaptive radiotherapy (ART), a notable innovation that addresses anatomy changes and optimizes the therapeutic ratio. ART utilizes advanced imaging techniques such as CT, MRI, and PET to modify the treatment plan based on observed anatomical changes and even biological changes during the course of treatment. The narrative review provides a comprehensive guide on ART for healthcare professionals and trainees in radiation oncology and anyone else interested in the topic. The incorporation of artificial intelligence in ART has played a crucial role in improving effectiveness, particularly in contour segmentation, treatment planning, and quality assurance. This has expedited the process to render online ART feasible, lowered the burden for radiation oncology practitioners, and enhanced the precision of dynamically personalized treatment. Current technical and clinical progress on ART is discussed in this review, highlighting the ongoing development of imaging technologies and AI and emphasizing their contribution to enhancing the applicability and effectiveness of ART.

Abstract: Colorectal cancer (CRC) is the second-leading cause of cancer-related mortality worldwide. CRC mortality results almost exclusively from metastatic disease (mCRC) for which systemic chemotherapy is often a preferred therapeutic option. Biomarker-based stratification of mCRC enables the use of precision therapy based on individual tumor mutational profiles. Activating mutations in the RAS/RAF/MAPK pathway downstream of EGFR signaling have, until recently, limited the use of EGFR-targeted therapies for mCRC; however, the development of anti-RAS and anti-RAF therapies together with improved strategies to limit compensatory signaling pathways is resulting in improved survival rates in several highly lethal mCRC sub-types (e.g., BRAF-mutant). The use of fluoropyrimidine (FP)-based chemotherapy regimens to treat mCRC continues to evolve contributing to improved long-term survival. Future advances in chemotherapy for mCRC will need to position development relative to the advances made in precision oncology.

Abstract: Acute lymphoblastic leukemia (ALL) is the most common disease in pediatric oncology. The history of developmental therapeutics for ALL began in the 1960s with the repetition of “unreliable” medical interventions against this lethal disease. By the 1990s, the development of multi-agent chemotherapy and various types of supportive care rendered ALL treatable. Highly sophisticated, molecular, diagnostic techniques have enabled highly accurate prediction of the relapse risk, and the application of risk-adapted treatments has increased the survival rate in the standard-risk group to nearly 100% in most European nations and North America. Incorporation of state-of-the-art, molecularly targeted agents and novel treatments, including cell and immunotherapy, is further improving outcomes even in the high-risk group. On the other hand, the financial burden of treating children with ALL has increased, imperiling the availability of these diagnostic and treatment strategies to patients in low- and middle-income countries (LMICs). The fundamental treatment strategy, consisting of corticosteroid and classical cytotoxic therapy, has achieved fairly good outcomes and should be feasible in LMICs as well. The present review will discuss the history of developmental therapeutics for childhood ALL in various countries through an extensive literature review with the aim of proposing a model for a treatment backbone for pediatric ALL. The discussion will hopefully benefit LMICs and be useful as a base for future clinical trials of novel treatments.

Abstract: Iron (Fe) and copper (Cu), essential transition metals, play pivotal roles in various cellular processes critical to cancer biology, including cell proliferation, mitochondrial respiration, distant metastases, and oxidative stress. The emergence of ferroptosis and cuproptosis as distinct forms of non-apoptotic cell death has heightened their significance, particularly in connection with these metal ions. While initially studied separately, recent evidence underscores the interdependence of ferroptosis and cuproptosis. Studies reveal a link between mitochondrial copper accumulation and ferroptosis induction. This interconnected relationship presents a promising strategy, especially for addressing refractory cancers marked by drug tolerance. Harnessing the toxicity of iron and copper in clinical settings becomes crucial. Simultaneous targeting of ferroptosis and cuproptosis, exemplified by the combination of sorafenib and elesclomol-Cu, represents an intriguing approach. Strategies targeting mitochondria further enhance the precision of these approaches, providing hope for improving treatment outcomes of drug-resistant cancers. Moreover, the combination of iron chelators and copper-lowering agents with established therapeutic modalities exhibits a synergy that holds promise for the augmentation of anti-tumor efficacy in various malignancies. This review elaborates on the complex interplay between ferroptosis and cuproptosis, including their underlying mechanisms, and explores their potential as druggable targets in both cancer research and clinical settings.

Abstract: Simple Summary Today, a significant issue in treating the most common cancers is their resistance to current treatment options like chemotherapy, radiotherapy, or immunotherapy. Drug combinations and/or dual inhibitors offer a promising alternative strategy to overcome this resistance. The purpose of this review is to present various existing options for the simultaneous administration of distinct drugs. Abstract Extensive research is underway to develop new therapeutic strategies to counteract therapy resistance in cancers. This review presents various strategies to achieve this objective. First, we discuss different vectorization platforms capable of releasing drugs in cancer cells. Second, we delve into multitarget therapies using drug combinations and dual anticancer agents. This section will describe examples of multitarget therapies that have been used to treat solid tumors.

Abstract: Cancer remains a leading cause of mortality worldwide, with metastasis significantly contributing to its lethality. The metastatic spread of tumor cells, primarily through the bloodstream, underscores the importance of circulating tumor cells (CTCs) in oncological research. As a critical component of liquid biopsies, CTCs offer a non-invasive and dynamic window into tumor biology, providing invaluable insights into cancer dissemination, disease progression, and response to treatment. This review article delves into the recent advancements in CTC research, highlighting their emerging role as a biomarker in various cancer types. We explore the latest technologies and methods for CTC isolation and detection, alongside novel approaches to characterizing their biology through genomics, transcriptomics, proteomics, and epigenetic profiling. Additionally, we examine the clinical implementation of these findings, assessing how CTCs are transforming the landscape of cancer diagnosis, prognosis, and management. By offering a comprehensive overview of current developments and potential future directions, this review underscores the significance of CTCs in enhancing our understanding of cancer and in shaping personalized therapeutic strategies, particularly for patients with metastatic disease.

Abstract: Autoimmune atrophic gastritis (AAG) is a chronic condition characterized by the presence of atrophy in the oxyntic mucosa due to anti-parietal cell antibodies. This review provides a comprehensive and up-to-date overview of autoimmune atrophic gastritis, reporting recent evidence on epidemiology, pathogenesis, diagnosis, clinical presentation, risk of malignancies, and management. The prevalence of AAG has been estimated at between 0.3% and 2.7% in the general population. The diagnosis of AAG is based on a combination of the serologic profile and the histological examination of gastric biopsies. Patients with AAG are often asymptomatic but can also have dyspeptic or reflux symptoms. The atrophy of the oxyntic mucosa leads to iron and vitamin B12 malabsorption, which may result in anemia and neurological affections. Autoimmune atrophic gastritis is associated with an increased risk of type I neuroendocrine tumors (NETs) and gastric cancer, with an incidence rate of 2.8% and 0.5% per person/year, respectively. Management is directed to reinstate vitamins and iron and to prevent malignancies with endoscopic surveillance. In conclusion, atrophic autoimmune gastritis is an infrequent condition, often asymptomatic and misdiagnosed, that requires an early diagnosis for appropriate vitamin supplementation and endoscopic follow-up for the early diagnosis of NETs and gastric cancer.

Abstract: Simple Summary Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of pancreatic cancers. It is considered one of the deadliest cancers due to its high metastatic potential and drug resistance. This review discusses various targets and nanoparticle-based delivery systems developed, tested, and approved for the effective diagnosis and targeted treatment of PDAC. Abstract Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest cancers, presents significant challenges in diagnosis and treatment due to its aggressive, metastatic nature and lack of early detection methods. A key obstacle in PDAC treatment is the highly complex tumor environment characterized by dense stroma surrounding the tumor, which hinders effective drug delivery. Nanotechnology can offer innovative solutions to these challenges, particularly in creating novel drug delivery systems for existing anticancer drugs for PDAC, such as gemcitabine and paclitaxel. By using customization methods such as incorporating conjugated targeting ligands, tumor-penetrating peptides, and therapeutic nucleic acids, these nanoparticle-based systems enhance drug solubility, extend circulation time, improve tumor targeting, and control drug release, thereby minimizing side effects and toxicity in healthy tissues. Moreover, nanoparticles have also shown potential in precise diagnostic methods for PDAC. This literature review will delve into targeted mechanisms, pathways, and approaches in treating pancreatic cancer. Additional emphasis is placed on the study of nanoparticle-based delivery systems, with a brief mention of those in clinical trials. Overall, the overview illustrates the significant advances in nanomedicine, underscoring its role in transcending the constraints of conventional PDAC therapies and diagnostics.

Abstract: Background: Robot-assisted partial nephrectomy (RAPN) is increasingly being employed in the management of renal cell carcinoma (RCC) and it is expanding in the field of complex renal tumors. The aim of this systematic review was to consolidate and assess the results of RAPN when dealing with entirely central hilar masses and to examine the various methods used to address the surgical difficulties associated with them. Methods: A thorough literature search in September 2023 across various databases focused on RAPN for renal hilar masses, adhering to PRISMA guidelines. The primary goal was to evaluate RAPN’s surgical and functional outcomes, with a secondary aim of examining different surgical techniques. Out of 1250 records, 13 full-text manuscripts were reviewed. Results: Evidence is growing in favor of RAPN for renal hilar masses. Despite a predominance of retrospective studies and a lack of long-term data, RAPN shows positive surgical outcomes and preserves renal function without compromising cancer treatment effectiveness. Innovative suturing and clamping methods are emerging in surgical management. Conclusions: RAPN is a promising technique for managing renal hilar masses in RCC, offering effective surgical outcomes and renal function preservation. The study highlights the need for more long-term data and prospective studies to further validate these findings.

Abstract: Simple Summary Endometrial cancer is the fourth most common female malignancy in high socioeconomic index nations and the sixth most common cancer in women worldwide. The disease incidence has increased globally by 132% in the last 30 years, and this trend is set to continue in light of an ageing population and increasing levels of obesity and diabetes. Although more women than ever before are dying of endometrial cancer, the mortality rates are falling due to recent advances in early diagnosis and treatment. Our understanding of the molecular drivers of endometrial cancer has increased substantially, and doctors are now, for the first time, starting to translate this knowledge into the true personalisation of care. This review summarises the recent advances in the field and identifies avenues for future exploration. Abstract Endometrial cancer is the sixth commonest cancer in women worldwide, with over 417,000 diagnoses in 2020. The disease incidence has increased by 132% over the last 30 years and is set to continue to rise in response to an ageing population and increasing global rates of obesity and diabetes. A greater understanding of the mechanisms driving endometrial carcinogenesis has led to the identification of potential strategies for primary disease prevention, although prospective evaluation of their efficacy within clinical trials is still awaited. The early diagnosis of endometrial cancer is associated with improved survival, but has historically relied on invasive endometrial sampling. New, minimally invasive tests using protein and DNA biomarkers and cytology have the potential to transform diagnostic pathways and to allow for the surveillance of high-risk populations. The molecular classification of endometrial cancers has been shown to not only have a prognostic impact, but also to have therapeutic value and is increasingly used to guide adjuvant treatment decisions. Advanced and recurrent disease management has also been revolutionised by increasing the use of debulking surgery and targeted treatments, particularly immunotherapy. This review summarises the recent advances in the prevention, diagnosis and treatment of endometrial cancer and seeks to identify areas for future research.

Abstract: Simple Summary The prevalence of cancer related to the digestive system keeps rising. We examined the 2024 literature on gastric cancer. Apart from surgery, which remains the primary treatment option for gastric cancer, immunotherapy and therapeutic targeting are becoming increasingly significant in the management of this disease. Following gastric cancer surgery, a multidisciplinary approach is required, with nutritionists and psychologists playing fundamental roles. Abstract Due to the high death rate associated with gastric cancer, a great deal of research has been conducted on this disease. The goal of this paper was to start a trimestral review of 2024 for the year that had just started. The scientific literature from 1 January 2024 was chosen with consideration of the the guidelines of the European Society of Medical Oncology (ESMO), which are updated with new findings but not systematically reviewed annually. We used the search term “gastric cancer” to find the most current publications in the PubMed database related to the prognosis and treatment of gastric cancer. As previously said, the only articles that satisfied the inclusion criteria were those from 2024. Articles with case reports were eliminated since they had nothing to do with our research. The treatment of gastric cancer is the focus of the majority of articles from 2024. The primary research axes include surgery and immunonutrition, immunotherapy and Helicobacter pylori, and therapeutic targets. Patients with GC may experience less psychological, social, and financial hardship if the recently identified markers discovered in circulation are better assessed and validated. This could be achieved by either including the markers in an artificial intelligence-based diagnostic score or by using them in conjunction with traditional diagnostic methods. Due to the rising death rate associated with GC, funding for research into diagnosis, prognosis, therapy, and therapeutic targets is essential.

Abstract: Artificial intelligence (AI) is currently becoming a leading field in data processing [...]

Abstract: Simple Summary The role of gender in oncology is an issue that is starting to be recognized as being of extreme importance in the last few years. While breast cancer is commonly perceived as a female-only disease, it does also occur in men, although rarely, thus opening relevant gender issues. Breast cancer in men is much less studied, with most knowledge coming from research on female breast cancer; however, several crucial differences have begun to be discovered between male and female patients. For example, the gender-specific impact and magnitude of risks conferred by breast cancer genetic risk factors are emerging, and they should be taken into consideration for a proper personalized clinical management. Overall, addressing all the challenges and the open issues regarding breast cancer genetic predisposition, including gender, will have an important clinical impact on the management of patients of both sexes. Abstract Among neoplastic diseases, breast cancer (BC) is one of the most influenced by gender. Despite common misconceptions associating BC as a women-only disease, BC can also occur in men. Additionally, transgender individuals may also experience BC. Genetic risk factors play a relevant role in BC predisposition, with important implications in precision prevention and treatment. The genetic architecture of BC susceptibility is similar in women and men, with high-, moderate-, and low-penetrance risk variants; however, some sex-specific features have emerged. Inherited high-penetrance pathogenic variants (PVs) in BRCA1 and BRCA2 genes are the strongest BC genetic risk factor. BRCA1 and BRCA2 PVs are more commonly associated with increased risk of female and male BC, respectively. Notably, BRCA-associated BCs are characterized by sex-specific pathologic features. Recently, next-generation sequencing technologies have helped to provide more insights on the role of moderate-penetrance BC risk variants, particularly in PALB2, CHEK2, and ATM genes, while international collaborative genome-wide association studies have contributed evidence on common low-penetrance BC risk variants, on their combined effect in polygenic models, and on their role as risk modulators in BRCA1/2 PV carriers. Overall, all these studies suggested that the genetic basis of male BC, although similar, may differ from female BC. Evaluating the genetic component of male BC as a distinct entity from female BC is the first step to improve both personalized risk assessment and therapeutic choices of patients of both sexes in order to reach gender equality in BC care. In this review, we summarize the latest research in the field of BC genetic predisposition with a particular focus on similarities and differences in male and female BC, and we also discuss the implications, challenges, and open issues that surround the establishment of a gender-oriented clinical management for BC.

Abstract: Simple Summary The estrogen receptor (ER) plays a critical role in the initiation and progression of breast cancer. Utilizing specialized therapies aimed at the ER has been effective in many instances and is commonly employed in breast cancer treatment protocols. The selection of therapy depends on multiple factors, including the menopausal status, breast cancer stage, and unique tumor attributes. These therapies can function independently as monotherapy, or in conjunction or sequential alignment with other treatments, based on the distinct characteristics of the breast cancer and the patient’s overall health. Furthermore, current research endeavors are focused on producing newer and more precise therapies for breast cancer, which include strategies to combat resistance mechanisms. The objective of this review is to provide a snapshot of the existing landscape and sketch out future paths for the progression of HR+ breast cancer treatments currently under clinical development. Abstract The hormone receptor-positive (HR+) type is the most frequently identified subtype of breast cancer. HR+ breast cancer has a more positive prognosis when compared to other subtypes, such as human epidermal growth factor protein 2-positive disorder and triple-negative disease. The advancement in treatment outcomes for advanced HR+ breast cancer has been considerably elevated due to the discovery of cyclin-dependent kinase 4/6 inhibitors and their combination effects with endocrine therapy. However, despite the considerable effectiveness of tamoxifen, a selective estrogen receptor modulator (SERMs), and aromatase inhibitors (AI), the issue of treatment resistance still presents a significant challenge for HR+ breast cancer. As a result, there is a focus on exploring new therapeutic strategies such as targeted protein degradation and covalent inhibition for targeting ERα. This article discusses the latest progress in treatments like oral selective ER degraders (SERDs), complete estrogen receptor antagonists (CERANs), selective estrogen receptor covalent antagonists (SERCAs), proteolysis targeting chimera (PROTAC) degraders, and combinations of CDK4/6 inhibitors with endocrine therapy. The focus is specifically on those compounds that have transitioned into phases of clinical development.

Abstract: Simple Summary A promising approach to combat aggressive prostate cancer involves androgen receptor degraders, which break down the crucial protein driving cancer progression. In contrast to traditional drugs, these degraders offer a potential solution to drug resistance. Methods like PROTACs have shown promise in reducing androgen receptor levels in cells and clinical benefits in patients. Six PROTACs and two other degraders have entered early clinical trials for potential treatment. While progress has been made in understanding these degraders, it is essential to stay updated on emerging developments. This article provides an overview of advancements in this field since 2020. Abstract Induced protein degradation has emerged as an innovative drug discovery approach, complementary to the classical method of suppressing protein function. The androgen receptor signaling pathway has been identified as the primary driving force in the development and progression of lethal castration-resistant prostate cancer. Since androgen receptor degraders function differently from androgen receptor antagonists, they hold the promise to overcome the drug resistance challenges faced by current therapeutics. Proteolysis-targeting chimeras (PROTACs), monomeric degraders, hydrophobic tagging, molecular glues, and autophagic degradation have demonstrated their capability in downregulating intracellular androgen receptor concentrations. The potential of these androgen receptor degraders to treat castration-resistant prostate cancer is substantiated by the advancement of six PROTACs and two monomeric androgen receptor degraders into phase I or II clinical trials. Although the chemical structures, in vitro and in vivo data, and degradation mechanisms of androgen receptor degraders have been reviewed, it is crucial to stay updated on recent advances in this field as novel androgen receptor degraders and new strategies continue to emerge. This review thus provides insight into recent advancements in this paradigm, offering an overview of the progress made since 2020.

Abstract: Simple Summary We summarize the current knowledge of the signaling pathways involved in anticancer drug-induced cell death. We discuss the common signaling pathways of apoptotic cell death, antiapoptotic pathways, non-apoptotic cell death mechanisms (autophagic, necrotic, and other), signaling pathways involved in the death of drug-sensitive and -resistant tumor cells (with emphasis on c-Jun/activator protein 1 and crosstalk with mitochondrial and endoplasmic reticulum pathways), and therapeutic implications of the modification of signaling pathways leading to cell death (with emphasis on cell death-related gene targeting, interactions of drug resistance factors in drug-resistant cells, and the unfolded protein response pathway). We provide suggestions for the restoration of these altered signaling pathways to potentially restore the drug sensitivity of tumor cells. Abstract Anticancer drugs induce apoptotic and non-apoptotic cell death in various cancer types. The signaling pathways for anticancer drug-induced apoptotic cell death have been shown to differ between drug-sensitive and drug-resistant cells. In atypical multidrug-resistant leukemia cells, the c-Jun/activator protein 1 (AP-1)/p53 signaling pathway leading to apoptotic death is altered. Cancer cells treated with anticancer drugs undergo c-Jun/AP-1–mediated apoptotic death and are involved in c-Jun N-terminal kinase activation and growth arrest- and DNA damage-inducible gene 153 (Gadd153)/CCAAT/enhancer-binding protein homologous protein pathway induction, regardless of the p53 genotype. Gadd153 induction is associated with mitochondrial membrane permeabilization after anticancer drug treatment and involves a coupled endoplasmic reticulum stress response. The induction of apoptosis by anticancer drugs is mediated by the intrinsic pathway (cytochrome c, Cyt c) and subsequent activation of the caspase cascade via proapoptotic genes (e.g., Bax and Bcl-xS) and their interactions. Anticancer drug-induced apoptosis involves caspase-dependent and caspase-independent pathways and occurs via intrinsic and extrinsic pathways. The targeting of antiapoptotic genes such as Bcl-2 enhances anticancer drug efficacy. The modulation of apoptotic signaling by Bcl-xS transduction increases the sensitivity of multidrug resistance-related protein-overexpressing epidermoid carcinoma cells to anticancer drugs. The significance of autophagy in cancer therapy remains to be elucidated. In this review, we summarize current knowledge of cancer cell death-related signaling pathways and their alterations during anticancer drug treatment and discuss potential strategies to enhance treatment efficacy.

Abstract: Objective: In a previous study, we proved that an experienced urologist is more likely to adapt to the Hugo RAS system. Based on this, we further examine various parameters in this study. Parameters included in this study consisted of console time, functional outcomes, and oncological outcomes. Materials and Methods: A total of 60 patients who underwent robot-assisted radical prostatectomy (RARP) performed by a single surgeon using the da Vinci (DV) system (n = 30) or the Hugo RAS system (n = 30) between March 2023 and August 2023 were included in the analysis. The intraoperative operative time was categorized into vesicourethral anastomosis time and overall console time. Functional and oncological outcomes were documented at the 1st and 3rd postoperative months. Parametric and non-parametric methods were adopted after checking skewness and kurtosis, and an α value of 5% was used to determine the significance. Results: The vesicourethral anastomosis time was significantly lengthened (Hedge’s g: 0.87; 95% confidence interval (CI): 0.34–1.39; J factor = 0.987). However, the overall console time was not affected. The functional (postoperative 3rd month: p = 0.130) and oncological outcomes (postoperative 3rd month: p = 0.103) were not significantly different. We also found that the adverse effect on surgical specimens and positive surgical margins was not affected (p = 0.552). Conclusion: During the process of adaptation, although intricate motions (such as the vesicourethral anastomosis time) would be lengthened, the overall console time would not change remarkably. In this process, the functional and oncological outcomes would not be compromised. This encourages urologists to adopt the Hugo RAS system in RARP if they have previous experiences of using the DV system, since their trifecta advantage would not be compromised.

Abstract: Simple Summary Glioblastoma (GBM) poses a formidable challenge as a central nervous system tumor with extremely limited responsiveness to conventional treatments. While immunotherapeutic approaches have shown success in treating other solid tumors, their effectiveness against GBM is limited. Our review systematically addresses the intrinsic features of GBM that hinder the success of both standard therapies and immunotherapies. Furthermore, we comprehensively analyze all the immune-based approaches currently undergoing clinical evaluation for GBM, both as standalone treatments and in combination with standard therapy or other immunotherapies. Abstract Despite decades of research and the best up-to-date treatments, grade 4 Glioblastoma (GBM) remains uniformly fatal with a patient median overall survival of less than 2 years. Recent advances in immunotherapy have reignited interest in utilizing immunological approaches to fight cancer. However, current immunotherapies have so far not met the anticipated expectations, achieving modest results in their journey from bench to bedside for the treatment of GBM. Understanding the intrinsic features of GBM is of crucial importance for the development of effective antitumoral strategies to improve patient life expectancy and conditions. In this review, we provide a comprehensive overview of the distinctive characteristics of GBM that significantly influence current conventional therapies and immune-based approaches. Moreover, we present an overview of the immunotherapeutic strategies currently undergoing clinical evaluation for GBM treatment, with a specific emphasis on those advancing to phase 3 clinical studies. These encompass immune checkpoint inhibitors, adoptive T cell therapies, vaccination strategies (i.e., RNA-, DNA-, and peptide-based vaccines), and virus-based approaches. Finally, we explore novel innovative strategies and future prospects in the field of immunotherapy for GBM.

Abstract: The incidence of skin cancer is rising globally, posing a significant public health threat. An early and accurate diagnosis is crucial for patient prognoses. However, discriminating between malignant melanoma and benign lesions, such as nevi and keratoses, remains a challenging task due to their visual similarities. Image-based recognition systems offer a promising solution to aid dermatologists and potentially reduce unnecessary biopsies. This research investigated the performance of four unified convolutional neural networks, namely, YOLOv3, YOLOv4, YOLOv5, and YOLOv7, in classifying skin lesions. Each model was trained on a benchmark dataset, and the obtained performances were compared based on lesion localization, classification accuracy, and inference time. In particular, YOLOv7 achieved superior performance with an Intersection over Union (IoU) of 86.3%, a mean Average Precision (mAP) of 75.4%, an F1-measure of 80%, and an inference time of 0.32 s per image. These findings demonstrated the potential of YOLOv7 as a valuable tool for aiding dermatologists in early skin cancer diagnosis and potentially reducing unnecessary biopsies.