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Topic Review
Manipulating EVs for Therapeutic Applications
Extracellular vesicles (EVs) receive special attention from clinicians due to their assumed usefulness as prognostic markers, immune modulators and physiological delivery tools. The latter application, that supports the reduction of side effects of treatment, is still fraught with many challenges, including established methods for loading EVs with selected cargo and directing them towards target cells. EVs could be loaded with selected cargo either in vitro using several physicochemical techniques, or in vivo by modification of parental cell. Otherwise, EVs may be passively supplemented with selected cargo, such as miRNAs or siRNA. Furthermore, recent findings imply that antigen-specific antibody light chains could coat the surface of EVs to increase the specificity of cell targeting. In addition, the route of EVs’ administration also determines their bioavailability and eventually induced therapeutic effect.
  • 899
  • 03 Jul 2020
Topic Review
Therapy for Brain Metastases
This manuscript reviews the impact of tumor biology and molecular profiles on the management paradigm for BM patients and critically analyzes the current landscape of SRS, with a specific focus on integration with systemic therapy. We also discuss emerging treatment strategies combining SRS and ICIs, the impact of timing and the sequencing of these therapies around SRS, the effect of corticosteroids, and review post-treatment imaging findings, including pseudo-progression and radiation necrosis.
  • 899
  • 29 Mar 2022
Topic Review
Vitamins and Cancer
There is a large body of evidence suggesting a strong correlation between vitamin intake as well as vitamin blood concentrations with the occurrence of certain types of cancer. The direction of association between the concentration of a given vitamin and cancer risk is tumor specific.
  • 899
  • 19 Nov 2021
Topic Review
Cancer Stem Cells in TNBC
Triple negative breast cancer (TNBC) remains an aggressive disease due to the lack of targeted therapies and low rate of response to chemotherapy that is currently the main treatment modality for TNBC. Breast cancer stem cells (BCSCs) are a small subpopulation of breast tumors and recognized as drivers of tumorigenesis. TNBC tumors are characterized as being enriched for BCSCs. Growing evidence has shown that breast cancer stem cells are associated with tumor initiation and metastasis and may play a critical role in chemoresistance. Multiple targets against breast cancer stem cells are now under investigation. Recent advances in the role of breast cancer stem cells in triple negative breast cancer and the identification of cancer stem cell biomarkers have paved the way for the development of new targeted therapies.
  • 899
  • 17 Dec 2021
Topic Review
Autophagy in Tumor Immune System
Autophagy is a stress-induced process that eliminates damaged organelles and dysfunctional cargos in cytoplasm, including unfolded proteins. Autophagy is involved in constructing the immunosuppressive microenvironment during tumor initiation and progression. It appears to be one of the most common processes involved in cancer immunotherapy, playing bidirectional roles in immunotherapy. Accumulating evidence suggests that inducing or inhibiting autophagy contributes to immunotherapy efficacy. Exploring autophagy targets and their modifiers to control autophagy in the tumor microenvironment is an emerging strategy to facilitate cancer immunotherapy. 
  • 899
  • 17 Oct 2022
Topic Review
Metabolic Biomarkers of Colorectal Cancer
Metabolic biomarkers of colorectal cancer (CRC) can be found in several matrices obtained from human body, such as breath, urine, feces, blood, intestinal gas, and tissue. Metabolic CRC biomarkers consist of small molecules, including volatile organic compounds (VOCs), which patterns (profiles) can be acquired by analytical techniques and be used to study the presence and progression of disease in the organism. Gas chromatography-mass spectrometry is a technique that allows to analyze volatiles and other classes of compounds of different chemical groups. Molecular profiles may indicate very specific biochemical ongoing processes in a biological system. Comparisons of metabolic profiles and the processing of this data using statistical tools can potentially enacoloble to distinguish diseased subjects from healthy ones.
  • 898
  • 15 Feb 2021
Topic Review
Biomarkers of Small Cell Lung Cancer
Small cell lung cancer (SCLC) is a high-grade neuroendocrine malignancy with an aggressive behavior and dismal prognosis. 5-year overall survival remains a disappointing 7%. Genomically, SCLCs are homogeneous compared to non-small cell lung cancers and are characterized almost always by functional inactivation of RB1 and TP53 with no actionable mutations. Additionally, SCLCs histologically appear uniform. Thus, SCLCs are managed as a single disease with platinum-based chemotherapy remaining the cornerstone of treatment. Recent studies have identified expression of dominant transcriptional signatures which may permit classification of SCLCs into four biologically distinct subtypes, namely, SCLC-A, SCLC-N, SCLC-P, and SCLC-I. These groups are readily detectable by immunohistochemistry and also have potential predictive utility for emerging therapies, including PARPi, immune checkpoint inhibitors, and DLL3 targeted therapies. In contrast with their histology, studies have identified that SCLCs display both inter- and intra-tumoral heterogeneity. Identification of subpopulations of cells with high expression of PLCG2 has been linked with risk of metastasis. SCLCs also display subtype switching under therapy pressure which may contribute furthermore to metastatic ability and chemoresistance. 
  • 898
  • 26 Oct 2022
Topic Review
Non-Invasive Biomarkers for Immunotherapy with Hepatocellular Carcinoma
Tumor biomarkers are cellular and molecular products linked directly or indirectly to the presence of cancer cells that are an expression of the tumor’s intrinsic characteristics and can be identified, measured, and analyzed by specific tests.  Currently, there is an increasing interest in developing novel techniques to extract information on tumor biology directly from patient’s body fluids in a non-invasive way. Liquid biopsy, a non-invasive approach of tumor biomarkers detection, permits a dynamic picture of HCC’s evolution and response to therapy. 
  • 897
  • 20 Oct 2022
Topic Review
Low-Grade Gliomas
Low-Grade Gliomas (LGGs) represent a diverse group of brain tumors originating from glial cells, characterized by their unique histopathological and molecular features. Here offers a comprehensive exploration of LGGs, shedding light on their subtypes, histological and molecular aspects. By delving into the World Health Organization’s grading system, 5th edition, various specificities were added due to an in-depth understanding of emerging laboratory techniques, especially genomic analysis.
  • 897
  • 18 Dec 2023
Topic Review
Bruton’s Tyrosine Kinase Signaling in Tumor Microenvironment
Protein tyrosine kinase Bruton’s tyrosine kinase (BTK) is essential for B cell maturation and proliferation. Dysregulation of BTK signaling in B cells leads to B cell lymphoma. In addition to B cells, BTK is also expressed in other types of immune cells including myeloid derived suppressor cells (MDSC), dendritic cells, mast cells and macrophages, all of which comprise the tumor microenvironment in solid cancers.
  • 897
  • 25 Oct 2022
Topic Review
Causal Diagrams in Oncology
Causal diagrams can be used to facilitate patient-specific decision-making by showing what data should be used and by explicitly representing the assumptions needed to combine data obtained from different sources.
  • 896
  • 26 Aug 2022
Topic Review
PD-1/PD-L1-Based Immunotherapy for Metastatic Triple-Negative Breast Cancer
Triple-negative breast cancer (TNBC) refers to a type of breast cancer in which the immunohistochemistry of the cancer tissue is negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2), and it accounts for 15–20% of all breast cancer patients. Because of its rapid progression, most patients with TNBC have progressed to the more malignant and aggressive metastatic TNBC (mTNBC), with a shorter survival period by the time they seek medical attention. The majority of breast cancer deaths are caused by mTNBC. According to pathological characteristics, it lacks specific therapeutic targets, and it cannot be completely removed surgically due to unclear distant micro-metastases. Therefore, treatment of mTNBC is usually based on chemotherapy. However, according to clinical statistics, the overall response rate (ORR‘) of mTNBC with single-agent chemotherapy is only 10–30%, and with the best multi-drug combination chemotherapy regimen it is only 63%. The average pathologically complete response (pCR) to mTNBC with multi-drug combination chemotherapy regimen is about 30–40%. In summary, the benefit of chemotherapy for patients with mTNBC is not promising. The search for treatments with high clearance, good targeting, and few side effects has become a major focus of medical research.
  • 896
  • 07 Sep 2022
Topic Review
Targeting Glucose Metabolism to Overcoming Drug Resistance
The “Warburg effect” consists of a metabolic shift in energy production from oxidative phosphorylation to glycolysis. The continuous activation of glycolysis in cancer cells causes rapid energy production and an increase in lactate, leading to the acidification of the tumour microenvironment, chemo- and radioresistance, as well as poor patient survival. Nevertheless, the mitochondrial metabolism can be also involved in aggressive cancer characteristics. The metabolic differences between cancer and normal tissues can be considered the Achilles heel of cancer, offering a strategy for new therapies. One of the main causes of treatment resistance consists of the increased expression of efflux pumps, and multidrug resistance (MDR) proteins, which are able to export chemotherapeutics out of the cell. Cells expressing MDR proteins require adenosine triphosphate (ATP) to mediate the efflux of their drug substrates. Thus, inhibition of the main energy-producing pathways in cancer cells, not only induces cancer cell death per se, but also overcomes multidrug resistance. 
  • 896
  • 24 Jan 2024
Topic Review
3 Cycles of 177Lu-PSMA Therapy
The [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) has emerged as a successful treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC). 
  • 896
  • 23 Jun 2021
Topic Review
SBRT-PATHY
Encouraging SBRT-PATHY-clinical outcomes, together with immunohistochemical and gene-expression analyses of surgically removed abscopal-tumor sites, suggested that delivery of the high-dose radiation to the partial (hypoxic) tumor volume, with optimal timing based on the homeostatic fluctuation of the immune response and sparing the peritumoral immune-environment, would significantly enhance the immune-mediated anti-tumor effects.
  • 895
  • 14 Jan 2021
Topic Review
Ferroptosis in Non-Small Cell Lung Cancer
As a main subtype of lung cancer, the current situation of non-small cell lung cancer (NSCLC) remains severe worldwide with a 19% survival rate at 5 years. As the conventional therapy approaches, such as chemotherapy, radiotherapy, targeted therapy, and immunotherapy, gradually develop into therapy resistance, searching for a novel therapeutic strategy for NSCLC is urgent. Ferroptosis, an iron-dependent programmed necrosis, has now been widely considered as a key factor affecting the tumorigenesis and progression in various cancers. 
  • 895
  • 13 Dec 2021
Topic Review
Cutaneous Immune-Related Adverse Events
Dermatologic complications arise as the earliest and most frequently observed adverse events among all immune-related adverse events (irAEs), affecting between 30 and 50% of patients on Immune checkpoint inhibitors (ICIs). The symptoms may significantly impair patients’ quality of life, and even lead to a pause of immunotherapy treatment. Fortunately, the majority of cirAEs seem to be mild and manageable, but there are still a few serious events (grade III or IV) being observed. Maculopapular rash, pruritus, lichenoid eruptions, and vitiligo are the most widely reported cutaneous adverse events. Severe cutaneous adverse reactions (SCARs), consisting of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug rash with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), are rare but potentially life-threatening. Other less-frequent manifestations include ICI-induced dermatomyositis, Sweet syndrome, interstitial granulomatous dermatitis, pityriasis rubra pilaris-like erythroderma, and lupus-like cutaneous reaction.
  • 895
  • 28 Apr 2022
Topic Review
Diagnosis of Retroperitoneal Sarcoma
Soft tissue sarcomas (STS) are an uncommon and biologically heterogeneous group of tumors arising from mesenchymal cells. The incidence is estimated at five cases per 100,000 people per year. Retroperitoneal sarcomas (RPS) account for 10–15% of all STS, and their management depends on their anatomical characteristics and histotype. Due to their very low incidence, it is recommended that RPS be treated in reference centers and evaluated by an experienced multidisciplinary team (MDT). In Spain, the Spanish Group for Research in Sarcomas (GEIS) brings together experts from various specialties to promote research on sarcomas and improve treatment results.
  • 895
  • 25 Sep 2023
Topic Review
Oligometastatic Adenocarcinoma of the Esophagus
Esophageal adenocarcinoma is an aggressive cancer of increasing incidence and is associated with poor prognosis. The early recognition of synchronous and metachronous oligometastasis in esophageal adenocarcinoma may allow for prompt intervention and potentially improved survival. However, curative approaches to oligometastatic esophageal disease remain unproven and may represent an area of emerging divergence of opinion for surgical and medical oncologists. We sought to identify the current understanding and evidence for management of oligometastatic esophageal adenocarcinoma by performing a thorough review of the available literature
  • 894
  • 10 Sep 2021
Topic Review
Cervical Cancer
Cervical cancer is one of the most common malignancies in women worldwide and its management remains challenging and complex. As Cytochrome4Z1 (CYP4Z1) is overexpressed in many tumours, its expression in cervical cancer is unknown. Therefore, the present study aimed to evaluate CYP4Z1 expression in cervical cancers. Methods: CYP4Z1 expression was immunohistochemically assessed in 100 cases of cervical cancers along with ten normal cervix tissues, and the enzyme’s relationship to several clinicopathological features and survival was explored. Results: CYP4Z1 was strongly expressed in 55% of cervical cancer patients. Normal cervix samples were negative for CYP4Z1 expression. Importantly, this expression was significantly found in patients with the late stage of the disease, lymph node metastasis, and high tumour invasion (p < 0.05). Interestingly, CYP4Z1 expression was significantly correlated with shorter survival times of cervical cancer patients. Univariate analysis showed that CYP4Z1 expression, tumour stage, lymph node metastasis, and tumour invasion were significantly correlated with patient survival (p < 0.05). The multivariate analysis revealed that only CYP4Z1 expression and tumour stage were significantly correlated with patient survival (p < 0.05). Conclusions: CYP4Z1 expression is associated with cervical cancer patients’ survival and may serve as an independent predictor of poor prognosis in cervical cancer patients. 
  • 894
  • 22 Sep 2021
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