Cancer is characterized by abnormal cell proliferation. Cyclins and cyclin-dependent kinases (CDKs) have been recognized as essential regulators of the intricate cell cycle, orchestrating DNA replication and transcription, RNA splicing, and protein synthesis. Dysregulation of the CDK pathway is prevalent in the development and progression of human cancers, rendering cyclins and CDKs attractive therapeutic targets. Several CDK4/6 inhibitors have demonstrated promising anti-cancer efficacy and have been successfully translated into clinical use, fueling the development of CDK-targeted therapies. With this enthusiasm for finding novel CDK-targeting anti-cancer agents, there have also been exciting advances in the field of targeted protein degradation through innovative strategies, such as using proteolysis-targeting chimera, heat shock protein 90 (HSP90)‍-mediated targeting chimera, hydrophobic tag-based protein degradation, and molecular glue. With a focus on the translational potential of cyclin- and CDK-targeting strategies in cancer, this review presents the fundamental roles of cyclins and CDKs in cancer. Furthermore, it summarizes current strategies for the proteasome-dependent targeted degradation of cyclins and CDKs, detailing the underlying mechanisms of action for each approach. A comprehensive overview of the structure and activity of existing CDK degraders is also provided. By examining the structure‍‒‍activity relationships, target profiles, and biological effects of reported cyclin/CDK degraders, this review provides a valuable reference for both CDK pathway-targeted biomedical research and cancer therapeutics.

Cancer immunotherapy targeting the PD-1/PD-L1 pathway has demonstrated efficacy across a range of common solid tumors and some hematopoietic malignancies. Despite these groundbreaking successes, the clinical development of other 'checkpoint inhibitors' targeting molecules like TIM-3, TIGIT, ICOS and others, has largely fallen short, often showing minimal clinical benefit even in combination with anti-PD therapy. This article explores three key hypotheses that help explain the disparity in therapeutic success: (1) the absence of tumor- specific immunosuppressive logic in many checkpoint targets, (2) the dominance-but not redundancy-of immune evasion mechanisms within the tumor microenvironment (TME), and (3) the emergence of therapy-induced resistance. This is not intended as a comprehensive review of the literature. Instead, it highlights select evidence to explain past failures and to illuminate a more strategic, biologically informed path forward.

Lung cancer remains one of the most prevalent and lethal malignancies worldwide, responsible for nearly 1.8 million deaths annually, which accounts for approximately 18.7% of global cancer-related mortality. Cisplatin, a highly effective and widely utilized anticancer drug, is particularly effective against solid tumors and serves as a cornerstone of adjuvant chemotherapy for lung cancer. Despite continuous optimization of cisplatin-based chemotherapy regimens, the emergence of cisplatin resistance frequently results in treatment failure, significantly limiting its clinical utility and therapeutic efficacy. To address this challenge, researchers have extensively investigated the biological mechanisms underlying cisplatin resistance, including impaired DNA repair pathways and inhibition of apoptosis. Among these mechanisms, epigenetic regulation-encompassing DNA methylation, histone modifications, and noncoding RNA (ncRNA) regulation-has emerged as a critical factor in mediating cisplatin resistance by modulating gene expression and signaling pathways. This review comprehensively explores the role of epigenetic mechanisms in cisplatin resistance in lung cancer, highlighting recent research findings and their potential implications for developing strategies to overcome drug resistance.

Breast cancer is the most prevalent cancer in women. Anthracyclines are commonly used as the first line of treatment, often combined with other agents, including trastuzumab. Despite their efficacy, both drugs pose a risk of cardiotoxicity, which may impair patients' quality of life (QoL) and hinder treatment persistence. Anthracycline-induced cardiotoxicity is dose-dependent and generally irreversible, whereas trastuzumab is associated with potentially reversible cardiac dysfunction. This review discusses the risk factors and biological mechanisms underlying chemotherapy-induced cardiotoxicity in breast cancer and explores effective strategies for prevention and treatment. It has been demonstrated that several cardioprotective strategies, such as treatments with angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), beta-blockers, and dexrazoxane, can help lessen cardiotoxic effects. A better understanding of cardioprotective strategies may help optimize cancer treatment without compromising cardiovascular function.

Doxorubicin is an antitumor antibiotic. It is often used in veterinary medicine to treat and extend the lives of dogs with cancer. A cardiotoxic side effect can lead to heart failure and treatment discontinuation. This systematic review and meta-analysis aimed to evaluate the drug's cardiotoxic effects on the ejection fraction (EF) of dogs in doxorubicin protocols. The search was done in eight databases, with a total of 3587 articles screened, resulting in fifteen eligible articles included. A report on the included studies' methods and results was done. It also assessed the risk of bias. Thirteen articles demonstrated cardiac changes in echocardiography with different routes of administration (intravenous and intracoronary). The intracoronary route was more toxic, and in all six studies performed, there was heart failure. The intravenous route caused heart failure in six of the nine studies. A meta-analysis showed this drug worsened heart disease. It included four studies where it significantly lowered the EF. Overall, the intervention produced a mean reduction of 21.24% in EF. This review shows doxorubicin's impact on cardiac function. It reveals the need for careful monitoring of each patient.

Brain tumors, particularly gliomas, are among the most lethal malignancies, with high mortality driven by a delayed diagnosis and limited therapeutic efficacy. A central challenge lies in the presence of the blood‑brain barrier (BBB), which severely impedes the delivery of systemically administered therapeutics to tumor sites. Addressing this clinical urgency, nanoparticle (NP)‑based delivery systems have emerged as a transformative strategy to enhance brain‑specific drug accumulation, minimize off‑target toxicity and improve treatment outcomes. The present review systematically examined the recent advances in nanocarrier technologies for targeted brain tumor therapy, including liposomes, solid lipid NPs, dendrimers, polymeric nanoplatforms and inorganic nanomaterials. The design principles, mechanisms for BBB traversal, therapeutic payload compatibility and tumor‑targeting capabilities of NP technologies demonstrated in preclinical models have also been highlighted. In addition to drug delivery, emerging applications of nanocarriers in gene therapy were explored and the impact of protein corona formation on NP behavior in vivo was discussed. Finally, current translational bottlenecks were identified and future design considerations to achieve clinically viable, precision‑targeted nanomedicines for brain tumors were outlined.

The B-cell lymphoma-2 (Bcl-2) family proteins, key regulators of apoptosis, are frequently dysregulated in cancer, tipping the balance of cell survival and apoptosis in favor of survival. The ubiquitin-proteasome system (UPS) is a critical cellular machinery that controls the Bcl-2 levels through regulation of protein stability. This review delves into the intricate interplay between the proteasome and Bcl-2 family members, exploring how proteasome-mediated degradation impacts cell survival and proliferation to influence cancer progression. We discuss the therapeutic potential of targeting the proteasome-Bcl-2 axis, including the use of proteasome inhibitors as anticancer agents. We examine their mechanisms of action, clinical efficacy, and limitations while exploring emerging strategies to overcome these challenges.

N6-methyladenosine (m6A) is the most prevalent internal modification of eukaryotic mRNA, playing a crucial role in the regulation of gene expression. Methyltransferase-like 3 (METTL3), a key catalytic component of the m6A methyltransferase complex, is primarily responsible for the deposition of m6A on target RNA. Recent studies have revealed that METTL3 contributes to diverse pathological processes, particularly tumorigenesis, through both m6A-dependent and independent mechanisms. As a result, METTL3 has attracted increasing interest as a potential therapeutic target across various cancer types. This review summarizes recent advances in the discovery of small molecules targeting METTL3, including substrate-competitive inhibitors, allosteric inhibitors, and proteolysis-targeting chimeras (PROTACs). It also discusses the strategies in their discovery, the associated structural features, and the remaining challenges and future directions in this field. Overall, these efforts provide valuable insights into the design and discovery of METTL3-targeted therapeutics with potential clinical applications.

Bone cancer remains a life-threatening malignancy predominantly affecting pediatric and adolescent populations, with tyrosine kinase inhibitors (TKIs) emerging as promising therapeutic agents; however, their clinical utility is limited by poor bioavailability, systemic toxicity, and inadequate tumor targeting. Recent advancements in nanocarrier-based delivery systems have significantly mitigated these limitations by enhancing targeted accumulation of TKIs at tumor sites, reducing off-target effects, and enabling controlled drug release. Various nanocarrier platforms, including liposomes, polymeric nanoparticles, micelles, dendrimers, metal- and metal oxide-based nanoparticles, carbon-based carriers, polymeric implants, and hydroxyapatite-based systems, have been systematically evaluated for their efficacy in delivering TKIs for bone cancer therapy. This review further examines the impact of nanoparticle size on cellular uptake and tumor penetration, with emphasis on liposomal and proteinaceous carriers (albumin-bound and transferrin-conjugated nanoparticles) that optimize tumor selectivity while minimizing systemic toxicity. Inorganic nanocarriers such as gold, silver, and metal oxides also demonstrate potential for multimodal therapeutic and diagnostic applications. Notwithstanding these advances, challenges including drug resistance, toxicity, and regulatory barriers remain, necessitating ongoing efforts to optimize nanocarrier formulations. This comprehensive review provides critical insights into the evolving landscape of nanotechnology-driven TKI delivery strategies aimed at enhancing therapeutic outcomes in bone cancer management.

Melanoma is a type of aggressive cancer distinguished by its high propensity for recurrence, the development of metastases, and an unfavorable outlook for recovery. Treatment modalities for melanoma encompass surgery, immunotherapy, and targeted therapies. In recent decades, berberine has garnered attention for its significant anticancer properties across various cancer types. This review systematically examines the molecular mechanisms of berberine in melanoma, particularly its modulation of critical signaling pathways, including B-RAF/MEK/ERK, PI3K/AKT, and NF-κB, which are essential for regulating melanoma cell proliferation and promoting apoptosis. Furthermore, berberine activates AMP-activated protein kinase, leading to the inhibition of cyclooxygenase-2, thereby reducing melanoma cell migration and invasion through decreased inflammation and enhanced cellular energy regulation. It also induces mitochondrial dysfunction and oxidative stress, promoting apoptosis while simultaneously inhibiting epithelial-to-mesenchymal transition, a key process in metastasis. Additionally, berberine modulates the immune microenvironment through Toll-like receptors, cytokine networks, and the regulation of various immune cells, thereby enhancing its antitumor effects. Recent studies have shown that the therapeutic effect of berberine is enhanced when used in combination with other therapies, especially immune checkpoint inhibitors, to improve antitumor immune responses. These findings highlight the potential of berberine as a multi-targeted agent for the treatment of melanoma, providing an avenue for further clinical exploration and integration into therapeutic strategies.

The advent of immune checkpoint inhibitors has introduced innovative therapeutic paradigms for the management of human epidermal growth factor receptor 2 (HER2)-negative advanced gastric or gastroesophageal junction cancer (GC/GEJC). However, the efficacy and safety of programmed cell death protein 1 (PD-1) inhibitors combined with chemotherapy versus chemotherapy alone in patients with HER2-negative advanced GC/GEJC remain contentious. The comparability among different subgroups is not fully understood, necessitating the identification of optimal patient demographics and the exploration of potential biomarkers.

Ferroptosis is a nonapoptotic form of cell death characterized by lethal membrane lipid peroxidation. This mechanism was first characterized in cancer cells well over a decade ago, and there is much enthusiasm for the concept that certain cancers may be treated by inducing ferroptosis. However, therapies that engage ferroptosis have yet to enter clinical testing. In this Review, we highlight the gap between our rapidly expanding knowledge of the ferroptosis mechanism and its translation into cancer therapies. We discuss the known challenges that may be slowing ferroptosis therapies from reaching the clinic.

The emergence of immune checkpoint inhibitors (ICIs) have provided a new perspective for cancer immunotherapy. Immune checkpoint inhibitors significantly improve the survival prognosis of patients with various advanced cancers by inhibiting immune checkpoint molecules, thereby releasing the suppression of T cells by tumor microenvironment, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Immune checkpoint inhibitor (ICI) therapy, while effective, gives rise to distinct immune-related adverse events (irAEs), including cardiovascular toxicities, necessitating focused research efforts to better understand and address these specific complications. The myocarditis-associated toxicity has been extensively studied. This article reviews the latest clinical and preclinical literature on the epidemiology and pathogenesis of ICI-related atherosclerosis, explores the pathophysiological mechanisms by which ICIs promote atherosclerosis, and discusses risk assessment, identification and monitoring methods, and intervention strategies for ICI treatment related atherosclerosis.

"Glutamine addiction" is a hallmark metabolic feature of many cancer cells. Driven by the "Warburg effect," tumor cells exhibit an increased reliance on glutamine uptake and metabolism to sustain rapid proliferation and survival. As such, precise modulation of glutamine metabolic pathways has emerged as a promising strategy for cancer therapy. Alanine - serine - cysteine transporter 2 (ASCT2), a key glutamine transporter, is frequently overexpressed in a variety of cancer cells, facilitating elevated glutamine influx to meet the metabolic demands of malignant cells. Accordingly, pharmacological inhibition of ASCT2 represents an attractive approach to reduce intracellular glutamine availability and suppress tumor cell growth. This review provides a comprehensive overview of ASCT2, including its structural and functional characteristics, recent progress in small-molecule inhibitor development, and the potential for future therapeutic applications.

Breast cancer is the most common cancer and the main cause of death because of malignant tumors in women, worldwide. The impact of Crocus sativus on several cancers has been discussed. Recent studies provide evidence regarding the anticancer properties of C. sativus and its bioactive constituents against breast cancer. This study aims to systematically review the efficacy of this botanical drug and its constituents on breast cancer, and their mechanism of action for the first time. Due to the lack of human studies in this field, the present research focused on preclinical studies.

Tremella fuciformis (TF) is a valuable edible fungus rich in various nutrients, with TF polysaccharide (TFP) as its primary bioactive component. Extensive studies have demonstrated that TFP exhibits significant bioactivities, including antioxidant, antitumor, immunomodulatory, memory-enhancing, anti-inflammatory, hypoglycemic, and hypolipidemic effects, as well as skin-protective properties and gut microbiota modulation. Due to these multifunctional properties, TFP has garnered considerable attention in the food, pharmaceutical, and cosmetic industries. This review summarizes recent research on TFP, focusing on its preparation methods, structural characteristics, and diverse biological activities. Additionally, it provides a theoretical basis for the potential applications of TFP in the food, pharmaceutical, and cosmetic industries, while also discussing future research directions and development prospects.

Epithelial ovarian cancer (EOC), accounting for 90-95% of all ovarian cancer (OC) cases, is the most lethal gynaecological malignancy, primarily due to late-stage diagnosis and the development of chemoresistance. While initial responses to Platinum- and Taxane-based chemotherapy are favorable, nearly 70% of patients relapse within five years. Although signaling pathways such as PI3K/AKT, MAPK, NF-κB, Notch, and Wnt/β-catenin have been individually studied in the context of chemoresistance, recent evidence highlights the importance of dynamic feedback loops and crosstalk among these networks in sustaining the resistant phenotype. Moreover, dysregulated microRNAs (miRNAs), as post-transcriptional regulators, fine-tune these pathways, creating self-sustaining circuits that promote drug efflux, inhibit apoptosis, and maintain cancer stemness. Reciprocal regulation between miRNAs and signaling components establishes robust networks that amplify chemoresistant phenotypes. The review provides a comprehensive overview of the molecular mechanisms driving chemoresistance, emphasising critical elements of signalling pathways and associated miRNAs that contribute to resistance and may function as biomarkers or therapeutic targets to mitigate chemoresistance. To improve clinical outcomes, future research should focus on identifying resistance-associated miRNA signatures and targeting nodal points within miRNA-signaling networks, thereby enabling the development of personalized therapies to overcome drug resistance in EOC.

Doxorubicin is a commonly used antitumor drug for the treatment of various cancers. However, its clinical application is greatly restricted by its severe cardiotoxicity. At present, doxorubicin-induced cardiotoxicity is categorized into acute and chronic forms, depending on the dosage and duration of exposure, which may eventually lead to the occurrence of heart failure. The pathogenesis of doxorubicin cardiotoxicity is associated with oxidative stress, mitochondrial damage, calcium overload, dysregulation of autophagy, and apoptosis. In forensic medical practice, cases of poisoning or even cardiac death caused by doxorubicin showed no obvious changes in cardiac morphology through routine forensic pathological examinations. The paper aims to summarize the research on the mechanisms of action of doxorubicin-induced cardiotoxicity in recent years, analyze and discuss the possible pathways of cardiomyocyte injury caused by doxorubicin, and provide references for research on the mechanisms of doxorubicin-induced cardiotoxicity and forensic application.

FDA approval of selective CDK4/6 inhibitors (CDK4/6i) marked a groundbreaking development in cancer treatment. Decades of pre-clinical studies elucidated the route that certain cancer cells take to gain the cancer hallmark of uncontrolled proliferation, uncovering CDK4/6 as key players. Further investigation into the molecular underpinnings of this process revealed interconnected signaling between the CDK4/6 and estrogen receptor (ER) signaling axes, providing evidence that CDK4/6i would be particularly relevant in estrogen-driven cancers. Three FDA-approved CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, were independently developed and all exhibited efficacy against in vivo models of ER+ breast cancer. Clinical trials then confirmed the safety and efficacy of these drugs in patients. Ongoing clinical trials are now testing CDK4/6i in several other cancer models, including other hormone-driven cancers. Further mechanistic insights should reveal predictive biomarkers of response, and potential combination therapies to overcome resistance. This chapter provides an overview of the development of these drugs, their current utility, and their potential use in the treatment of multiple malignancies.

Steroid Hormone Receptors (SHRs) when bound to its ligand can act as transcription factors, which are responsible for transcription of important genes via hormone responsive element in our genome. Many studies have revealed the molecular mechanisms involved with SHRs. Cancer specific aberrant expression pattern of SHR and variation in their mechanism created an opportunity to specifically target SHRs for developing highly effective anti-cancer therapeutics. Further, these receptors can be targeted using different nanodelivery systems thus proving to be a potent target. The anticancer nanodelivery system can selectively target cancer cells due to the newly discovered aberrant nature of SHRs in cancer making it unique from other membrane bound receptors that are relatively more easily accessible as these are mostly overexpressed on the surface of the cells. One such interesting receptor which is present in the cytoplasm of the cells and ubiquitously expressed in both cancer and non-cancer cells is glucocorticoid receptor (GR). GR as studied earlier behaves in a unique way in cancer cells which facilitates the nanodelivery system including small molecules to selectively target cytoplasmic GR and hence makes the anticancer therapeutics more precise in its own way. Here, we will summarize the knowledge of SHR providing information about its role in its molecular mechanisms in cells and mostly to dig into its anticancer therapeutic roles in cancer cells. Most importantly how the lipid nanoformulation can modulate the SHRs ligand binding domain in cancer therapeutics is also discussed. This also deals with all the SHRs including estrogen, progesterone, mineralocorticoid receptors and androgen receptors.