Biochimica et Biophysica Acta. Reviews on Cancer

Angiogenesis is a crucial process for tissue development, repair, and tumor survival. Vascular endothelial growth factor (VEGF) is a key driver secreted by cancer cells, promoting neovascularization. While VEGF's role in angiogenesis is well-documented, its influence on the other aspects in tumor microenvironemt is less discussed. This review elaborates on VEGF's impact on intercellular interactions within the tumor microenvironment, including how VEGF affects pericyte proliferation and migration and mediates interactions between tumor-associated macrophages and cancer cells, resulting in PDL-1-mediated immunosuppression and Nrf2-mediated epithelial-mesenchymal transition...

Prostate cancer is unique compared to other major cancers due to the presence of multiple primary malignant foci in the majority of patients at the time of diagnosis. Each malignant focus has distinct somatic mutations and gene expression patterns, which represents a challenge for the development of prognostic tests for localized prostate cancer. Additionally, the molecular heterogeneity of advanced prostate cancer has important implications for management, particularly for patients with metastatic and locally recurrent cancer...

The Heat Shock Response (HSR) is a cellular stress reaction crucial for cell survival against stressors, including heat, in both healthy and cancer cells. Modulated electro-hyperthermia (mEHT) is an emerging non-invasive cancer therapy utilizing electromagnetic fields to selectively target cancer cells via temperature-dependent and independent mechanisms. However, mEHT triggers HSR in treated cells. Despite demonstrated efficacy in cancer treatment, understanding the underlying molecular mechanisms for improved therapeutic outcomes remains a focus...

Cancer vaccines, designed to activate the body's own immune system to fight against tumors, are a current trend in cancer treatment and receiving increasing attention. Cancer vaccines mainly include oncolytic virus vaccine, cell vaccine, peptide vaccine and nucleic acid vaccine. Over the course of decades of research, oncolytic virus vaccine T-VEC, cellular vaccine sipuleucel-T, various peptide vaccines, and DNA vaccine against HPV positive cervical cancer have brought encouraging results for cancer therapy, but are losing momentum in development due to their respective shortcomings...

The composition and pattern of dietary intake have emerged as key factors influencing aging, regeneration, and consequently, healthspan and lifespan. Cancer is one of the major diseases more tightly linked with aging, and age-related mortality. Although the role of nutrition in cancer incidence is generally well established, we are far from a consensus on how diet influences tumour development in different tissues. In this review, we will discuss how diet and dietary restrictions affect cancer risk and the molecular mechanisms potentially responsible for their effects...

Decitabine's early successful therapeutic outcomes in hematologic malignancies have led to regulatory approvals from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for addressing myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). These approvals have sparked keen interest in exploring the potential of decitabine for treating solid tumors. Continuous preclinical and clinical trials have proved that low doses of decitabine also bring benefits in treating solid tumors, and various proposed mechanisms attempt to explain the potential efficacy...

Pancreatic cancer (PC) remains a leading cause of mortality worldwide due to the absence of early detection methods and the low success rates of traditional therapeutic strategies. Drug resistance in PC is driven by its desmoplastic stroma, which creates a barrier that shields cancer niches and prevents the penetration of drugs. The PC stroma comprises heterogeneous cellular populations and non-cellular components involved in aberrant ECM deposition, immunosuppression, and drug resistance. These components can influence PC development through intricate and complex crosstalk with the PC cells...

Prostate cancer (PC) is the second most frequently diagnosed cancer and the fifth leading cause of cancer-related deaths in male population worldwide. Since the growth and progression of PC highly depend on the androgen pathway, androgen deprivation therapy (ADT) is the mainstay of systemic treatment. Enzalutamide is a second-generation antiandrogen, which is widely used for the treatment of advanced and metastatic PC. However, treatment failure and disease progression, caused by the emergence of enzalutamide resistant phenotypes, remains an important clinical challenge...

Renewed interest in tumor metabolism sparked an enthusiasm for dietary interventions to prevent and treat cancer. Changes in diet impact circulating nutrient levels in the plasma and the tumor microenvironment, and preclinical studies suggest that dietary approaches, including caloric and nutrient restrictions, can modulate tumor initiation, progression, and metastasis. Cancers are heterogeneous in their metabolic dependencies and preferred energy sources and can be addicted to glucose, fructose, amino acids, or lipids for survival and growth...

The tumour microenvironment (TME) is usually defined as a cell environment associated with tumours or cancerous stem cells where conditions are established affecting tumour development and progression through malignant cell interaction with non-malignant cells. The TME is made up of endothelial, immune and non-immune cells, extracellular matrix (ECM) components and signalling molecules acting specifically on tumour and non-tumour cells. Breast cancer (BC) is the commonest malignant neoplasm worldwide and the main cause of mortality in women globally; advances regarding BC study and understanding it are relevant for acquiring novel, personalised therapeutic tools...

Several clinical trials and experimental studies have recently shown that vitamin K (VK) supplementation benefits the human body. Specifically, VK participates in coagulation and is associated with cellular senescence and cancer. VK has a potential anticancer effect in various cancers, such as pancreatic and prostate cancers. Through anti-inflammatory and antioxidant effects, VK can prevent senescence and inhibit cancer metastasis. Therefore, cancer prognosis can be improved by preventing cellular senescence...

Cancer and its metastases arise from mutations of genes, drivers that promote a tumor's growth. Analyses of driver events provide insights into cancer cell history and may lead to a better understanding of oncogenesis. We reviewed 27 metastatic research studies, including pan-cancer studies, individual cancer studies, and phylogenetic analyses, and summarized our current knowledge of metastatic drivers. All of the analyzed studies had a high level of consistency of driver mutations between primary tumors and metastasis, indicating that most drivers appear early in cancer progression and are maintained in metastatic cells...

Canonically, the transcription factor interferon regulatory factor 5 (IRF5) is a key mediator of innate and adaptive immunity downstream of pathogen recognition receptors such as Toll-like receptors (TLRs). Hence, dysregulation of IRF5 function has been widely implicated in inflammatory and autoimmune diseases. Over the last few decades, dysregulation of IRF5 expression has been also reported in hematologic malignancies and solid cancers that support a role for IRF5 in malignant transformation, tumor immune regulation, clinical prognosis, and treatment response...

Ovarian cancer is a less common tumor in women compared to cervical or breast cancer, however it is more malignant and has worse outcomes. Ovarian cancer patients still have a five-year survival rate < 50% despite advances in therapy. Due to recent developments in immune checkpoint inhibitors (ICIs), cancer immunotherapy has attracted increased interest. Pyroptosis is a highly inflammatory form of cell death, which is essential for bridging innate and adaptive immunity, and is involved in immune regulation within the tumor microenvironment (TME)...

Glioblastoma multiforme is a highly malignant brain tumor with significant intra- and intertumoral heterogeneity known for its aggressive nature and poor prognosis. The complex signaling cascade that regulates this heterogeneity makes targeted drug therapy ineffective. The development of an optimal preclinical model is crucial for the comprehension of molecular heterogeneity and enhancing therapeutic efficacy. The ideal model should establish a relationship between various oncogenes and their corresponding responses...

Colorectal cancer (CRC) ranks among the leading cancers in terms of incidence and mortality in the Western world. Currently, there are no sufficient diagnostic markers that would enable an early diagnosis and efficient therapy. Unfortunately, a significant number of new CRC cases is detected in late stages, with distant metastases, therefore, new therapeutic approaches, which would alleviate the prognosis for advanced stages of CRC, are highly in demand. SNHG6 belongs to the group of long non-coding RNAs, which are a larger entity of RNAs consisting of >200 nucleotides...

Despite extensive research and refined therapeutic options, the survival for metastasized uveal melanoma (UM) patients has not improved significantly. UM, a malignant tumor originating from melanocytes in the uveal tract, can be asymptomatic and small tumors may be detected only during routine ophthalmic exams; making early detection and treatment difficult. UM is the result of a number of characteristic somatic alterations which are associated with prognosis. Although UM morphology and biology have been extensively studied, there are significant gaps in our understanding of the early stages of UM tumor evolution and effective treatment to prevent metastatic disease remain elusive...

Despite the extensive efforts to find effective therapeutic strategies, glioblastoma (GBM) remains a therapeutic challenge with dismal prognosis of survival. Over the last decade the role of stress responses in GBM therapy has gained a great deal of attention, since depending on the duration and intensity of these cellular programs they can be cytoprotective or promote cancer cell death. As such, initiation of the UPR, autophagy or oxidative stress may either impede or facilitate drug-mediated cell killing...

This review delves into the most recent research on the metabolic adaptability of cancer cells and examines how their metabolic functions can impact their progression into metastatic forms. We emphasize the growing significance of lipid metabolism and dietary lipids within the tumor microenvironment, underscoring their influence on tumor progression. Additionally, we present an outline of the interplay between metabolic processes and the epigenome of cancer cells, underscoring the importance regarding the metastatic process...

High-grade serous ovarian cancer (HGSOC) is the most frequent and aggressive type of epithelial ovarian cancer, with high recurrence rate and chemoresistance being the main issues in its clinical management. HGSOC is specifically challenging due to the metastatic dissemination via spheroids in the ascitic fluid. The HGSOC spheroids represent the invasive and chemoresistant cellular fraction, which is impossible to investigate in conventional two-dimensional (2D) monolayer cell cultures lacking critical cell-to-cell and cell-extracellular matrix interactions...