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The "Road" to Malignant Transformation from Endometriosis to Endometriosis-Associated Ovarian Cancers (EAOCs): An mTOR-Centred Review.

Ovarian cancer is an umbrella term covering a number of distinct subtypes. Endometrioid and clear-cell ovarian carcinoma are endometriosis-associated ovarian cancers (EAOCs) frequently arising from ectopic endometrium in the ovary. The mechanistic target of rapamycin (mTOR) is a crucial regulator of cellular homeostasis and is dysregulated in both endometriosis and endometriosis-associated ovarian cancer, potentially favouring carcinogenesis across a spectrum from benign disease with cancer-like characteristics, through an atypical phase, to frank malignancy. In this review, we focus on mTOR d

Inoperable Renal Malignant Glomus Tumor, the answers for all the "W's"?

Glomus tumor, arising from glomus bodies (specialized neurovascular structures involved in thermoregulation), commonly occurs in extremities and rarely in viscera. The spectrum of glomus tumors range from benign tumors to tumors with uncertain malignant potential to tumors of the malignant subtype. A vast majority of visceral glomus tumors are benign. Most common visceral tumors arise in the gastrointestinal tract. Glomus tumors of the kidney are a rare entity of which malignant glomus tumors are exceedingly rare. The index patients in the existing case reports were middle-aged males. We repor

Mediterranean Diet Food Components as Possible Adjuvant Therapies to Counteract Breast and Prostate Cancer Progression to Bone Metastasis.

Bone metastasis is a serious and often lethal complication of particularly frequent carcinomas, such as breast and prostate cancers, which not only reduces survival but also worsens the patients' quality of life. Therefore, it is important to find new and/or additional therapeutic possibilities that can counteract the colonization of bone tissue. High adherence to the Mediterranean diet (MD) is effective in the prevention of cancer and improves cancer patients' health, thus, here, we considered its impact on bone metastasis. We highlighted some molecular events relevant for the development of

Modeling the Bone Marrow Niche in Multiple Myeloma: From 2D Cultures to 3D Systems.

Multiple myeloma is a hematologic malignancy characterized by the clonal proliferation of plasma cells within the bone marrow. The tumor microenvironment plays a crucial role in multiple myeloma pathogenesis, progression, and drug resistance. Traditional two-dimensional cell culture models have been instrumental in multiple myeloma research. However, they fail to recapitulate the complex in vivo bone marrow microenvironment, leading to limited predictive value for clinical outcomes. Three-dimensional cell culture models emerged as more physiologically relevant systems, offering enhanced insigh

FDA-Approved Drugs Containing Amide Functionality in the Last Five Years (2021-2025): Pharmaceutical Use, Trends and Synthetic Approaches.

The amide functional group remains a cornerstone of medicinal chemistry, serving as an indispensable scaffold in the design of modern therapeutics. This review presents an analysis of FDA-approved drugs (small molecules and peptides with MW ®), amides form the structural backbone of peptidomimetics, enabling high-affinity binding to a viral protease. In precision oncology, as seen with adagrasib (Krazati®), the amide acts as a critical, metabolically stable linker that positions a covalent warhead for selective inhibition of a mutant kinase. This analysis underscores that amide's unique combin

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… Tovorafenib Approved on 23 April 2024, tovorafenib ( 69 , brand name Ojemda ® , Figure 53 ) is an oral, once-weekly, type II RAF kinase inhibitor developed for the treatment of pediatric brain tumors driven by alterations in the MAPK signaling pathway [ 218 , 219 ]. … It targets both mutant and wild-type RAF kinases, including BRAF V600 mutations, as well as BRAF fusions and rearrangements, helping to suppress tumor growth in BRAF-altered cancers [ 220 ]. …

The GH-IGF-SST system in hepatocellular carcinoma: biological and molecular pathogenetic mechanisms and therapeutic targets.

Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide. Different signalling pathways have been identified to be implicated in the pathogenesis of HCC; among these, GH, IGF and somatostatin (SST) pathways have emerged as some of the major pathways implicated in the development of HCC. Physiologically, GH-IGF-SST system plays a crucial role in liver growth and development since GH induces IGF1 and IGF2 secretion and the expression of their receptors, involved in hepatocytes cell proliferation, differentiation and metabolism. On the other hand, somatostatin receptors (SSTRs

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… In a currently completed Phase1b/2 study ( NCT01498952 ), an open-label, randomized study, MEDI-573 has been tested in combination with sorafenib, a small molecule inhibitor of several tyrosine protein kinases (VEGFR and PDGFR) and Raf kinases, in adult subjects with unresectable or metastatic HCC; however …

Keyword Index for Volume 90

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Emerging Frontiers in Colorectal Cancer Therapy: From Targeted Molecules to Immunomodulatory Breakthroughs and Cell-Based Approaches.

Colorectal cancer (CRC) is ranked as the second leading cause of cancer-related deaths globally, necessitating urgent advancements in therapeutic approaches. The emergence of groundbreaking therapies, including chimeric antigen receptor-T (CAR-T) cell therapies, oncolytic viruses, and immune checkpoint inhibitors, marks a transformative era in oncology. These innovative modalities, tailored to individual genetic and molecular profiles, hold the promise of significantly enhancing patient outcomes. This comprehensive review explores the latest clinical trials and advancements, encompassing targe

Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells.

Head and neck cancer (HNC) has frequently an aggressive course for the development of resistance to standard chemotherapy. Thus, the use of innovative therapeutic drugs is being assessed. Bortezomib is a proteasome inhibitor with anticancer effects. In vitro antitumoral activity of Bortezomib was investigated employing human tongue (SCC-15, CAL-27), pharynx (FaDu), salivary gland (A-253) cancer cell lines and a murine cell line (SALTO-5) originated from a salivary gland adenocarcinoma arising in BALB-neuT male mice transgenic for the oncogene neu. Bortezomib inhibited cell proliferation, trigg

Каннабиноиды в раке: Молекулярные механизмы смерти клеток и возможности перевода.

Каннабиноиды представляют собой терпенофенолические соединения, полученные из Cannabis sativa L., которые осуществляют широкий спектр биологической и фармакологической деятельности. Растущие данные свидетельствуют об их потенциале как модуляторов развития рака, особенно посредством подавления роста клеток опухоли, ангиогенеза и метастаза в различных моделях опухоли. В настоящем обзоре содержится всеобъемлющий обзор молекулярных механизмов, с помощью которых природные и синтетические каннабиноиды вызывают регулируемую смерть раковых клеток. Текущие данные свидетельствуют о том, что каннабиноиды

Critical considerations in the administration of antineoplastic therapy for patients with malignant solid tumors undergoing hemodialysis.

Patients with chronic kidney disease exhibit a higher risk of developing malignancies, and among those with end-stage renal disease (ESRD) on dialysis, approximately 7% are diagnosed with new-onset tumors within five years. Patients with ESRD who are receiving antineoplastic treatment exhibit a significantly higher incidence and greater severity of adverse effects associated with antineoplastic agents compared to individuals with normal renal function. This complexity involves multiple factors, including the therapy options and dose adjustment of antineoplastic agents, drug-related toxicities,

Precision Oncology-The Quest for Evidence.

The molecular characterization of patient tumors provides a rational and highly promising approach for guiding oncologists in treatment decision-making. Notwithstanding, genomic medicine still remains in its infancy, with innovators and early adopters continuing to carry a significant portion of the clinical and financial risk. Numerous innovative precision oncology trials have emerged globally to address the associated need for evidence of clinical utility. These studies seek to capitalize on the power of predictive biomarkers and/or treatment decision support analytics, to expeditiously and

" Nucleolus in Human Beasons: Ribosome Biogenesis " , " Nucleolar Survey " и " Terrapeutic Opportunities " .

Nucleolus превратился в динамичную и многофункциональную субядерную органилию, интегрирующую рибосомный биогенез с клеточным ростом и сигнализацией стресса. Регулирование нуклеолярной функции все чаще признается в качестве главного движителя человеческих заболеваний, связывающего изменённое рибосомное производство и нуклеолярное наблюдение с раком, рибосомопатиями, синдромами преждевременного старения, нейродегенерацией и иммунными расстройствами. В этом обзоре мы интегрируем структурные, молекулярные и болезнетворные перспективы нуклеолярной биологии для определения того, как рипосомный биоге

A Preclinical Evaluation of the Antitumor Activities of Edible and Medicinal Mushrooms: A Molecular Insight.

Cancer is the leading cause of morbidity and mortality around the globe. For certain types of cancer, chemotherapy drugs have been extensively used for treatment. However, severe side effects and the development of resistance are the drawbacks of these agents. Therefore, development of new agents with no or minimal side effects is of utmost importance. In this regard, natural compounds are well recognized as drugs in several human ailments, including cancer. One class of fungi, "mushrooms," contains numerous compounds that exhibit interesting biological activities, including antitumor activity

Molecular classification of gastric cancer: Towards a pathway-driven targeted therapy.

Gastric cancer (GC) is the third leading cause of cancer mortality worldwide. Although surgical resection is a potentially curative approach for localized cases of GC, most cases of GC are diagnosed in an advanced, non-curable stage and the response to traditional chemotherapy is limited. Fortunately, recent advances in our understanding of the molecular mechanisms that mediate GC hold great promise for the development of more effective treatment strategies. In this review, an overview of the morphological classification, current treatment approaches, and molecular alterations that have been c

Targeting Protein Degradation Pathways in Tumors: Focusing on their Role in Hematological Malignancies.

Cells must maintain their proteome homeostasis by balancing protein synthesis and degradation. This is facilitated by evolutionarily-conserved processes, including the unfolded protein response and the proteasome-based system of protein clearance, autophagy, and chaperone-mediated autophagy. In some hematological malignancies, including acute myeloid leukemia, misfolding or aggregation of the wild-type p53 tumor-suppressor renders cells unable to undergo apoptosis, even with an intact p53 DNA sequence. Moreover, blocking the proteasome pathway triggers lymphoma cell apoptosis. Extensive studie

Prediction of cancer drugs by chemical-chemical interactions.

Cancer, which is a leading cause of death worldwide, places a big burden on health-care system. In this study, an order-prediction model was built to predict a series of cancer drug indications based on chemical-chemical interactions. According to the confidence scores of their interactions, the order from the most likely cancer to the least one was obtained for each query drug. The 1(st) order prediction accuracy of the training dataset was 55.93%, evaluated by Jackknife test, while it was 55.56% and 59.09% on a validation test dataset and an independent test dataset, respectively. The propos

The Emerging Role of the FGF/FGFR Pathway in Gastrointestinal Stromal Tumor.

Gastrointestinal stromal tumors (GIST) are rare neoplasms of mesenchymal origin arising in the gastrointestinal tract. The vast majority are characterized by mutually exclusive activating mutations in KIT or Platelet-derived growth factor alpha (PDGFRA) receptors, or less frequently by succinate dehydrogenase complex (SDH) or NF1 inactivation, with very rare cases harboring mutant BRAF or RAS alleles. Approximately 5% of GISTs lack any of such mutations and are called quadruple wild-type (WT) GISTs. Recently, deregulated Fibroblast Growth Factor (FGF)/FGF-receptor (FGFR) signaling emerged as a

Past, Present, and a Glance into the Future of Multiple Myeloma Treatment.

Multiple myeloma (MM) is a challenging hematological cancer which typically grows in bone marrow. MM accounts for 10% of hematological malignancies and 1.8% of cancers. The recent treatment strategies have significantly improved progression-free survival for MM patients in the last decade; however, a relapse for most MM patients is inevitable. In this review we discuss current treatment, important pathways for proliferation, survival, immune suppression, and resistance that could be targeted for future treatments.

Precision medicine in nasopharyngeal carcinoma: comprehensive review of past, present, and future prospect.

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with high propensity for lymphatic spread and distant metastasis. It is prominent as an endemic malignancy in Southern China and Southeast Asia regions. Studies on NPC pathogenesis mechanism in the past decades such as through Epstein Barr Virus (EBV) infection and oncogenic molecular aberrations have explored several potential targets for therapy and diagnosis. The EBV infection introduces oncoviral proteins that consequently hyperactivate many promitotic pathways and block cell-death inducers. EBV infection is so prevalent in NPC pat