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Topic Review
Immunotherapy Drugs and Combinations of HNCSCC
Cutaneous squamous cell carcinoma (CSCC) is the second most common non-melanoma skin cancer. A majority of patients present with localized disease, but some can present with locally advanced or metastatic disease. Most of these advanced cases occur in the anatomical head and neck region and are associated with more aggressive disease, necessitating prompt and effective treatment. Prior to the emergence of immunotherapy, systemic treatment options were limited to platinum-based chemotherapy and salvaged with targeted epidermal growth factor therapy. These therapies were associated with poor efficacy and increased toxicity in an often frail, older population. Immunotherapy has dramatically improved outcomes in this patient population due to its favorable side effect profile, durable treatment response, and improved overall outcomes. 
  • 786
  • 29 Jan 2023
Topic Review
Immune Microenvironment in CNS Tumors
Gliomas are the most common primary brain tumors and are classified by the World Health Organization (WHO) as grade I–IV tumors based on molecular and genomic features, allowing a more accurate classification of patients. Given the transition from histological characterization, this newer molecular classification system enables precision medicine therapeutic selection and leads to a more accurate prediction of prognosis. Despite the evolution of such classifications and of immunotherapies, these tumors remain refractory to immune therapeutics. Understanding the microenvironment of gliomas and it's heterogeneity is key to discover potential future immunotherapeutic strategies. Recent findings show that immune activity against tumors may be dependent of the tumor microenvironment, especially in hot spots of immune reactivity like the invasive edge.
  • 785
  • 27 Aug 2021
Topic Review
Breast Cancer Aptamers
The aptamer was also tested in vivo with mice models and was able to inhibit breast cancer progression. This aptamer proves promising for therapeutic treatment of breast cancer and likely sensing as well due to its high specificity and affinity. The RNA aptamer pegaptanib sodium, commonly shortened to pegaptanib, binds only to the VEGF165isoform, and selectively binds with the heparin-binding site.
  • 785
  • 02 Dec 2021
Topic Review
The Interaction of COVID-19 and Lung Cancer Treatment
SARS-CoV-2 infection has dramatically impacted the real-world management of cancer patients. Given the higher risk of a longer and more severe course of COVID-19 disease in lung cancer patients, oncological services have been profoundly reorganized. The world’s leading professional organizations provided new recommendations for the diagnosis, treatment, and follow-up of lung cancer patients during the pandemic. Telemedicine was preferred for non-urgent visits, and screening programs were temporarily suspended, leading to possible diagnostic delays and an estimated increase of cause-specific mortality. The vaccination campaign has definitively inverted this negative trend, with the administration of the booster dose prioritized in frail immune-depressed patients. The efficacy and duration of a humoral immune response in cancer patients still represents an opened question, requiring further investigation in dedicated studies.
  • 784
  • 29 Apr 2022
Topic Review
Adrenocortical Carcinoma
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options in the advanced stages.
  • 783
  • 07 Apr 2021
Topic Review
Genetics in Epstein–Barr Virus-Associated Malignancies
Global genomic studies have detected the role of genomic alterations in the pathogenesis of Epstein–Barr virus (EBV)-associated tumors. EBV oncoproteins cause a vital shift of EBV from an infectious virus to an oncogenic form during the latent and lytic phase within the lymphoid B cells and epithelial cells. This epigenetic alteration modulates the virus and host genomes and inactivates and disrupts numerous tumor suppressors and signaling pathways. Genomic profiling has played the main role in identifying EBV cancer pathogenesis and its related targeted therapies. 
  • 783
  • 29 Mar 2022
Topic Review
Large B-Cell Lymphoma
Diffuse large B-cell lymphomas (DLBCLs) are aggressive B-cell neoplasms with considerable clinical, biologic, and pathologic diversity. The application of high throughput technologies to the study of lymphomas has yielded abundant molecular data leading to the identification of distinct molecular identities and novel pathogenetic pathways.
  • 783
  • 20 Jul 2021
Topic Review
HMGB1 in Cutaneous Melanoma
High-mobility Group Box 1 (HMGB1) is a nuclear protein that plays a key role in acute and chronic inflammation. HMGB1 is closely associated with cell survival and proliferation and may be directly involved in tumor cell metastasis development thanks to its ability to promote cell migration. HMGB1 is closely associated with cell survival and proliferation and may be directly involved in tumor cell metastasis development thanks to its ability to promote cell migration. 
  • 783
  • 24 Aug 2022
Topic Review
Necroptosis: Biological Relevance in Cancer
Necroptosis is a caspase independent form of regulated cell death, investigated as a novel therapeutic strategy to eradicate apoptosis resistant cancer cells. The process can be triggered by a variety of stimuli and is controlled by the activation of RIP kinases family as well as MLKL. The well-studied executor, RIPK1, is able to modulate key cellular events through the interaction with several proteins, acting as strategic crossroads of several molecular pathways. Little evidence is reported about the involvement of RIPK1 in tumorigenesis. Of particular interest is its contradictory role in cancer and its function in cell fate control. Targeting necroptosis might be a novel therapeutic intervention strategy in anticancer therapies as pharmacologically controllable event.
  • 782
  • 26 Feb 2021
Topic Review
Pediatric Gliomas
pLGGs or glioneuronal tumors (WHO grade 1 or 2) are highly heterogeneous entities. The most common single entity is pilocytic astrocytoma (0.91/100.000 patients age 0 to 19 years), followed by ganglioglioma, dysembryoplastic neuroepithelial tumor (DNET), and Grade 2 diffuse gliomas. High-grade gliomas of childhood are a histologically less heterogenic group of tumors with lower incidence compared to pLGGs (age-adjusted incidence, 0–19 years of age, is 0.26/100.000 without DIPGs). pHGGs consist of Grade 3 tumors like anaplastic astrocytomas (0.1/100.000 patients age 0 to 19 years) and anaplastic gangliogliomas, and Grade 4 tumors include GBM (0.18/100.000 patients age 0 to 19 years), DIPG (80% of brain stem tumors, which accounts for 15% of all CNS tumors), and gliomatosis cerebri, which is a highly infiltrative, special manifestation of HGG affecting multiple brain regions, not regarded as a separate subgroup any more.
  • 782
  • 08 Sep 2021
Topic Review
Metaplastic Carcinoma of the Breast
Metaplastic carcinoma of the breast (MpBC) is a very rare and aggressive type of breast cancer. Data focusing on MpBC are limited. Eligible articles about MpBC were identified by searching CASES SERIES gov and the MEDLINE bibliographic database for the period of 1 January 2010 to 1 June 2021 with the keywords metaplastic breast cancer, mammary gland cancer, neoplasm, tumor, and metaplastic carcinoma.
  • 781
  • 07 Jun 2023
Topic Review
Combined Strategies with PARP Inhibitors in Ovarian Cancer
Poly (ADP-ribose) polymerase (PARP) inhibitors are the first clinically approved drugs designed to exploit synthetic lethality, and were first introduced as a cancer-targeting strategy in 2005. They have led to a major change in the treatment of advanced ovarian cancer, and altered the natural history of a disease with extreme genetic complexity and defective DNA repair via homologous recombination (HR) pathway. Furthermore, additional mechanisms apart from breast related cancer antigens 1 and 2 (BRCA1/2) mutations can also result in HR pathway alterations and consequently lead to a clinical benefit from PARP inhibitors. Novel combinations of PARP inhibitors with other anticancer therapies are challenging, and better understanding of PARP biology, DNA repair mechanisms, and PARP inhibitor mechanisms of action is crucial. It seems that PARP inhibitor and biologic agent combinations appear well tolerated and clinically effective in both BRCA-mutated and wild-type cancers. They target differing aberrant and exploitable pathways in ovarian cancer, and may induce greater DNA damage and HR deficiency. The input of immunotherapy in ovarian cancer is based on the observation that immunosuppressive microenvironments can affect tumour growth, metastasis, and even treatment resistance. Several biologic agents have been studied in combination with PARP inhibitors, including inhibitors of vascular endothelial growth factor (VEGF; bevacizumab, cediranib), and PD-1 or PD-L1 (durvalumab, pembrolizumab, nivolumab), anti-CTLA4 monoclonal antibodies (tremelimumab), mTOR-(vistusertib), AKT-(capivasertib), and PI3K inhibitors (buparlisib, alpelisib), as well as MEK 1/2, and WEE1 inhibitors (selumetinib and adavosertib, respectively). Olaparib and veliparib have also been combined with chemotherapy with the rationale of disrupting base excision repair via PARP inhibition. Olaparib has been investigated with carboplatin and paclitaxel, whereas veliparib has been tested additionally in combination with temozolomide vs. pegylated liposomal doxorubicin, as well as with oral cyclophosphamide, and topoisomerase inhibitors. However, overlapping myelosuppression observed with PARP inhibitor and chemotherapy combinations requires further investigation with dose escalation studies. In this review, we discuss multiple clinical trials that are underway examining the antitumor activity of such combination strategies.
  • 781
  • 27 Sep 2023
Topic Review
Hyperoxia Effects in Cancer
Hyperoxia effects on cancer biology were explored following multiple pathways, using both in vitro cancer cell cultures and in vivo tumoral animal models. Experimental data support clinical evidences demonstrating that hyperoxia, mainly if prolonged, can induce lung injury and cerebral damage, and this can be counteracted by down-modulation of Akt, by low-dose vitamin D or aspirin.
  • 781
  • 10 Dec 2021
Topic Review
MiR-146a in Lung Cancer
Lung cancer is a well-known malignant tumor of the respiratory tract, which has caused a significant level of damage to human health in the 21st century. Micro-RNAs (miRNAs) are tiny, non-coding RNA stem-loop structures with a length of roughly 20–25 nucleotides that function as powerful modulators of mRNA and protein products of a gene. miRNAs may modulate many biological processes involving growth, differentiation, proliferation, and cell death and play a key role in the pathogenesis of various types of malignancies. Several accumulating pieces of evidence have proven that miRNA, especially miR-146a, are crucial modulators of innate immune response sequences. Changes in miR-146a expression levels have biomarker importance and possess a high potential as a therapeutic target in lung cancer. It retards epithelial-mesenchymal transition and promotes the therapeutic action of anticancer agents in lung cancer. Studies have also suggested that miR-146a affects gene expression through different signaling pathways viz.
  • 780
  • 07 May 2021
Topic Review
Aspirin and Colorectal Cancer Prevention in Lynch Syndrome
Cancer prevention in the era of precision medicine has to consider integrated therapeutic approaches. Therapeutic cancer prevention should be offered to selected cohorts with increased cancer risk. Undoubtedly, carriers of hereditary cancer syndromes have a well-defined high cancer risk. Lynch Syndrome is one of the most frequent hereditary syndromes; it is mainly associated with colorectal cancer (CRC). Nonsteroidal anti-inflammatory drugs and, in particular, aspirin use, has been associated with reduced CRC risk in several studies, initially with contradictory results; however, longer follow-up confirmed a reduced CRC incidence and mortality. The CAPP2 study recruited 861 Lynch syndrome participants randomly assigned to 600 mg of aspirin versus placebo. Like sporadic CRCs, a significant CRC risk reduction was seen after an extended follow-up, with a median treatment time that was relatively short (2 years). The ongoing CAPP3 will address whether lower doses are equally effective. Based on pharmacology and clinical data on sporadic CRCs, the preventive effect should also be obtained with low-dose aspirin. The leading international guidelines suggest discussing with Lynch syndrome carriers the possibility of using low-dose aspirin for CRC prevention. 
  • 780
  • 20 Apr 2022
Topic Review
MicroRNA in Epstein–Barr Virus-Associated Cancers
A conservative estimate suggests that almost 1.4 million of malignancies are associated with oncogenic viruses, including the hepatitis B virus, hepatitis C virus, Kaposi sarcoma-associated herpesvirus, human T lymphotropic virus type 1, human papillomaviruses, and Epstein–Barr virus (EBV). The oncogenic properties of these viruses are directly related to their ability to activate processes needed for cellular proliferation, survival, migration, and immune evasion. Among these viruses, EBV, formerly designated as the human herpesvirus type 4 (HHV-4), is a y-herpesvirus containing a linear, double-stranded DNA genome of ~172 kilobase pairs (kbp), encoding nearly 80 proteins and 46 functional small untranslated RNAs. The genetic material of EBV is enclosed in an icosahedral nucleocapsid surrounded by the viral tegument and lipid-containing outer envelope. EBV is transmitted through oral contact, particularly in the early years of life, usually without causing disease. EBV can also be transmitted through organ transplantation and blood transfusion. The life cycle of EBV primarily involves the infection of lymphocytes and potentially epithelial cells. Although EBV often exists as an asymptomatic infection, it is involved in the development of about 1.5% of all cancers worldwide. In fact, EBV was the first virus to have been directly associated with cancer in humans. EBV-associated neoplasms affect both immune-competent and immunocompromised hosts, including, for example, some organ transplant recipients. Immune dysregulation and genetic susceptibility are probable co-factors in most, if not all, EBV-associated cancers.
  • 779
  • 22 Sep 2021
Topic Review
Hedgehog Pathway
The hedgehog pathway, which plays a significant role in embryonic development and stem cell regulation, is activated in gastrointestinal cancers. Chemotherapy is widely used in cancer treatment. However, chemoresistance becomes a substantial obstacle in cancer therapy.
  • 779
  • 07 Sep 2021
Topic Review
IAPs in Cancer
The Inhibitor of Apoptosis (IAP) family of proteins has emerged as a potential pharmacological target in cancer. Abnormal expression of IAPs can lead to dysregulated cell suicide, promoting the development of different pathologies. In several cancer types, members of this protein family are overexpressed while their natural antagonist (Smac) appears to be downregulated, contributing to the acquisition of resistance to traditional therapy. 
  • 779
  • 12 Apr 2022
Topic Review
Systemic Therapy De-Escalation in Early-Stage Triple-Negative Breast Cancer
Early-stage triple negative breast cancer (TNBC) has been traditionally treated with surgery, radiation, and chemotherapy. The current standard of care systemic treatment of early-stage II and III TNBC involves the use of anthracycline-cyclophosphamide and carboplatin-paclitaxel with pembrolizumab in the neoadjuvant setting followed by adjuvant pembrolizumab per KEYNOTE-522. It is increasingly clear that not all patients with early-stage TNBC need this intensive treatment, thus paving the way for exploring opportunities for regimen de-escalation in selected subgroups. For T1a tumors (≤5 mm), chemotherapy is not used, and for tumors 6–10 mm (T1b) in size with negative lymph nodes, retrospective studies have failed to show a significant benefit with chemotherapy. In low-risk patients, anthracycline-free chemotherapy may be as effective as conventional therapy, as shown in some studies where replacing anthracyclines with carboplatin has shown non-inferior results for pathological complete response (pCR), which may form the backbone of future combination therapies.
  • 779
  • 19 Apr 2022
Topic Review
Ascorbate in Cancer Therapy
Cancer is a disease of high mortality, and its prevalence has increased steadily in the last few years. Ascorbate (ascorbic acid or vitamin C) is a potent water-soluble antioxidant that is produced in most mammals but is not synthesised endogenously in humans, which lack enzymes for its synthesis. Ascorbate has antioxidant effects that correspond closely to the dose administered. Interestingly, this natural antioxidant induces oxidative stress when given intravenously at a high dose, a paradoxical effect due to its interactions with iron. Importantly, this deleterious property of ascorbate can result in increased cell death. Although, historically, ascorbate has been reported to exhibit anti-tumour properties, this effect has been questioned due to the lack of available mechanistic detail. Recently, new evidence has emerged implicating ferroptosis in several types of oxidative stress-mediated cell death, such as those associated with ischemia–reperfusion. This effect could be positively modulated by the interaction of iron and high ascorbate dosing, particularly in cell systems having a high mitotic index. In addition, it has been reported that ascorbate may behave as an adjuvant of favourable anti-tumour effects in cancer therapies such as radiotherapy, radio-chemotherapy, chemotherapy, immunotherapy, or even in monotherapy, as it facilitates tumour cell death through the generation of reactive oxygen species and ferroptosis.
  • 779
  • 28 Jun 2022
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