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Topic Review
Stem Cell Theory of Cancer
The stem cell theory of cancer predicates that both normal and cancer stem cells can be induced into or released from dormancy depending on their multipotential constraints and microenvironment restraints. A unified theory of cancer predicts that even though genetic makeup in cancer dormancy maybe pivotal, cellular context must be paramount. After all, both normal stem cells and cancer stem cells proliferate and differentiate. They can be stationary and migratory. They can be static and dynamic. Importantly, gonadal germ cells are prototype stem cells and germ cell tumor of the testis (TGCT) is a model stem cell cancer.
  • 1.2K
  • 09 Feb 2022
Topic Review
The Microbiome in Pancreatic Ductal Adenocarcinoma
Pancreatic cancer is a highly lethal cancer and less than 10% of patients survive the 5-year mark. The molecular and biological underpinnings leading to this dismal prognosis are well-described, however, translation of these findings with subsequent improvement of the poor prognosis has been slow. The complex and dynamic accumulation of microbes, also called the microbiome, has attracted scientific interest in the pathogenesis of several diseases including pancreatic cancer. Since then, a limited number of significant findings were published pointing towards an important role of the microbiome in cancer, in particular pancreatic cancer.
  • 1.2K
  • 16 Dec 2022
Topic Review
COVID-19 Impact on Cancer-Related Care in America
COVID-19 impacted several health services, including cancer-related care. Its implications were significant due to the lapse in hospital resources, compounded by the delays stemming from the economic effects on patients’ jobs and medical coverage. Furthermore, reports suggesting an increased risk for morbidity and mortality from COVID-19 in patients with cancer and those on active cancer treatment caused additional fear and potential delays in seeking medical services.
  • 1.2K
  • 19 Jan 2023
Topic Review
Targeted Therapy for EWS-FLI1 in Ewing Sarcoma
Ewing sarcoma (EwS) is a highly aggressive and metastatic cancer in children and adolescents. Canonical therapy mainly comprises the combination of intensive chemotherapy, radiation, and local surgery, which give rise to acute and chronic adverse effects. Drugs targeting EwS without side effects are in urgent demand. Genetically, EwS is characterized by chromosomal translocations with a low mutation burden. As a result, the chimeric protein EWS-ETS, mainly EWS-FLI1(85%), is critical for the malignancy of EwS. EWS-FLI1 directly binds to GGAA microsatellites in enhancers and promotors of the target genes and recruits multiple transcription factors or epigenetic regulators to reprogramme the epigenome.
  • 1.2K
  • 17 Aug 2023
Topic Review
Mismatch Repair Deficiency
Universal MMR/MSI testing is standard of care for all patients with newly diagnosed CRC based on multi-society guidelines in the United States. Such testing is intended to identify patients with Lynch Syndrome due to a germline mutation in an MMR gene, but also detects those with sporadic dMMR/MSI-high CRCs.
  • 1.2K
  • 19 Feb 2021
Topic Review
MiRNA Epitranscriptomic Modifications in Cancer
MicroRNAs are small non-coding RNAs, acting as post-transcriptional regula- tors of gene expression. In the last two decades, their role in cancer as oncogenes (oncomir), as well as tumor suppressors, has been extensively demonstrated. Recently, epitranscriptomics, namely the study of RNA modifications, has emerged as a new field of great interest, being an additional layer in the regulation of gene expression. Almost all classes of eukaryotic RNAs, including miRNAs, undergo epitranscriptomic modifications. Alterations of RNA modification pathways have been de- scribed for many diseases—in particular, in the context of malignancies. 
  • 1.2K
  • 20 Jul 2021
Topic Review
JAK inhibitors and immune system
The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is aberrantly activated in many malignancies. Inhibition of this pathway via JAK inhibitors (JAKinibs) is therefore an attractive therapeutic strategy underlined by Ruxolitinib (JAK1/2 inhibitor) being approved for the treatment of myeloproliferative neoplasms. As a consequence of the crucial role of the JAK-STAT pathway in the regulation of immune responses, inhibition of JAKs suppresses the immune system. This review article provides a thorough overview of the current knowledge on JAKinibs’ effects on immune cells in the context of hematological malignancies. We also discuss the potential use of JAKinibs for the treatment of diseases in which lymphocytes are the source of the malignancy.
  • 1.2K
  • 23 Jun 2021
Topic Review
Antibody–Drug Conjugate for Cancer Treatment
Cancer, also known as malignant tumour or neoplasm, is a leading cause of death worldwide. One distinct feature from normal cells is that cancerous cells often overexpress protein on the cell membrane—for instance, the overexpression of human epidermal growth factor receptor 2. The expression of a specific protein on the cancerous cell surface acts as a marker that differentiates the normal cell and facilitates the recognition of cancerous cells. An emerging anticancer treatment, Antibody–Drug Conjugates (ADCs), utilises this unique feature to kill cancerous cells. ADCs consist of an antibody linked with a cytotoxic payload, mainly targeting the antigen found on cancerous cells. This design can increase the specificity in delivering the cytotoxin to the drug target, thus increasing the drug efficacy and reducing the side effect of cancer treatment due to off-target toxicities. 
  • 1.2K
  • 23 Oct 2023
Topic Review
Cancer Treatment-Induced Accelerated Aging
There is a growing concern about accelerated aging among the rapidly increasing number of cancer survivors. Clinically, “accelerated aging” phenotypes in cancer survivors include premature mortality and comorbidities – secondary cancers, frailty, chronic organ dysfunction, and cognitive impairment which can impact long-term health and quality of life in cancer survivors.
  • 1.2K
  • 28 Sep 2021
Topic Review
Cancer Vaccines
Therapeutic cancer vaccines target TAAs alongside adjuvant molecules that can elicit specific antibodies or cytotoxic immune responses against cancer cells. There are different ways to present TAAs to the immune system. DNA and RNA encoding TAAs or whole peptides can be recognized and processed by the APCs; tumor cell lines express TAAs and can chemotactically attract APCs; viral vectors transfect APCs after being loaded with prespecified antigens; finally, DCs act as APCs and can be loaded with TAAs.
  • 1.2K
  • 29 Mar 2022
Topic Review
Boron Neutron Capture Therapy
Boron neutron capture therapy (BNCT) is a type of targeted radiotherapy. BNCT shows promising results in treating lung cancer, recurrent head and neck cancer, sarcomas, and high grade brain tumors.
  • 1.2K
  • 29 Nov 2021
Topic Review
Vaccines for Human Papillomavirus-Associated Head and Neck Cancers
Human papillomavirus (HPV) is recognized as a significant risk factor for head and neck cancers worldwide, and it is the most common cause of oropharyngeal cancers in the United States. Prophylactic HPV vaccines have demonstrated effectiveness against oral infection of HPV 16 and HPV 18. There are also various strategies in development of therapeutic HPV vaccines underway.
  • 1.2K
  • 10 Jan 2022
Topic Review
MET in Non-Small-Cell Lung Cancer
Non-Small-Cell Lung Cancer (NSCLC) can harbour different MET alterations, such as MET overexpression (MET OE), MET gene amplification (MET AMP), or MET gene mutations. Retrospective studies of surgical series of patients with MET-dysregulated NSCLC have shown worse clinical outcomes irrespective of the type of specific MET gene alteration. On the other hand, earlier attempts failed to identify the ‘druggable’ molecular gene driver until the discovery of MET exon 14 skipping mutations (METex14). METex14 are rare and amount to around 3% of all NSCLCs. Patients with METex14 NSCLC attain modest results when they are treated with immune checkpoint inhibitors (ICIs). New selective MET inhibitors (MET-Is) showed a long-lasting clinical benefit in patients with METex14 NSCLC and modest activity in patients with MET AMP NSCLC. 
  • 1.2K
  • 19 Oct 2023
Topic Review
Bladder Cancer
The overwhelming majority of bladder cancers are transitional cell carcinomas. Albeit mostly monotonous, carcinomas in the bladder may occasionally display a broad spectrum of histological features that should be recognized by pathologists because some of them represent a diagnostic problem and/or lead prognostic implications. Sometimes these features are focal in the context of conventional transitional cell carcinomas, but some others are generalized across the tumor making its recognition a challenge. For practical purposes, the review distributes the morphologic spectrum of changes in architecture and cytology. Thus, nested and large nested, micropapillary, myxoid stroma, small tubules and adenoma nephrogenic-like, microcystic, verrucous, and diffuse lymphoepithelioma-like, on one hand, and plasmacytoid, signet ring, basaloid-squamous, yolk-sac, trophoblastic, rhabdoid, lipid/lipoblastic, giant, clear, eosinophilic (oncocytoid), and sarcomatoid, on the other, are revisited. Key histological and immunohistochemical features useful in the differential diagnosis are mentioned. In selected cases, molecular data associated with the diagnosis, prognosis, and/or treatment are also included.
  • 1.2K
  • 30 Dec 2020
Topic Review
Cutaneous Findings in NF1
Neurofibromatosis type 1 (NF1) is a complex autosomal dominant disorder associated with germline mutations in the NF1 tumor suppressor gene. NF1 belongs to a class of congenital anomaly syndromes called RASopathies, a group of rare genetic conditions caused by mutations in the Ras/mitogen-activated protein kinase pathway. Generally, NF1 patients present with dermatologic manifestations.
  • 1.2K
  • 02 Feb 2021
Topic Review
Dual Kinase Targeting in Leukemia
Pharmacological cancer therapy is often based on the concurrent inhibition of different survival pathways to improve treatment outcomes and to reduce the risk of relapses. While this strategy is traditionally pursued only through the co-administration of several drugs, the recent development of multi-targeting drugs (i.e., compounds intrinsically able to simultaneously target several macromolecules involved in cancer onset) has had a dramatic impact on cancer treatment.
  • 1.2K
  • 21 Feb 2021
Topic Review
Oncolytic Viruses in Controlled Trials
Oncolytic virotherapy is a promising antitumor therapeutic strategy. It is based on the ability of viruses to selectively kill cancer cells and induce host antitumor immune responses. However, the clinical outcomes of oncolytic viruses (OVs) vary widely. Therefore, we performed a meta-analysis to illustrate the efficacy and safety of oncolytic viruses. The Cochrane Library, PubMed, and EMBASE databases were searched for randomized controlled trials (RCTs) published up to January 31, 2020. The data for objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were independently extracted by two investigators from 11 studies that met the inclusion criteria. In subgroup analyses, the objective response rate benefit was observed in patients treated with oncolytic DNA viruses (odds ratio (OR) = 4.05; 95% confidence interval (CI): 1.96–8.33; p = 0.0002), but not in those treated with oncolytic RNA viruses (OR = 1.00, 95% CI: 0.66–1.52, p = 0.99). Moreover, the intratumoral injection arm yielded a statistically significant improvement (OR = 4.05, 95% CI: 1.96–8.33, p = 0.0002), but no such improvement was observed for the intravenous injection arm (OR = 1.00, 95% CI: 0.66–1.52, p = 0.99). Among the five OVs investigated in RCTs, only talimogene laherparepvec (T-VEC) effectively prolonged the OS of patients (hazard ratio (HR), 0.79; 95% CI: 0.63–0.99; p = 0.04). None of the oncolytic virotherapies improved the PFS (HR = 1.00, 95% CI: 0.85–1.19, p = 0.96). Notably, the pooled rate of severe AEs (grade ≥3) was higher for the oncolytic virotherapy group (39%) compared with the control group (27%) (risk difference (RD), 12%; risk ratio (RR), 1.44; 95% CI: 1.17–1.78; p = 0.0006). This review offers a reference for fundamental research and clinical treatment of oncolytic viruses. Further randomized controlled trials are needed to verify these results.
  • 1.2K
  • 14 Oct 2020
Topic Review
Pancreatic Ductal Adenocarcinoma Therapy
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in the US, and it is expected to be the second leading cause of cancer deaths by 2030. The lack of effective early screening tests and alarming symptoms with early undetectable micro-metastasis at the time of presentation play a vital role in the high death rate from pancreatic cancer. In addition to this, the low mutation burden in pancreatic cancer, low immunological profile, dense tumorigenesis stroma, and decreased tumor sensitivity to cytotoxic drugs contribute to the low survival rates in PDAC patients. Despite breakthroughs in chemotherapeutic and immunotherapeutic drugs, pancreatic cancer remains one of the solid tumors that exhibit meager curative rates.
  • 1.2K
  • 23 Jun 2021
Topic Review
Protein Lipidation
Proteins play indispensable roles in maintaining cell survival, and their functions are often regulated by post-translational modifications (PTMs), in which proteins are proteolytically cleaved or enzymatically conjugated with modifying groups. Various enzymes, including kinases, phosphatases, transferases, and ligases, catalyze approximately 500 discrete PTMs of a diverse set of proteins. PTMs regulate diverse activities of a colossal number of proteins. For example, various types of lipids can be covalently linked to proteins enzymatically or non-enzymatically. Protein lipidation is perhaps not as extensively studied as protein phosphorylation, ubiquitination, or glycosylation although it is no less significant than these modifications. Evidence suggests that proteins can be attached by at least seven types of lipids, including fatty acids, lipoic acids, isoprenoids, sterols, phospholipids, glycosylphosphatidylinositol anchors, and lipid-derived electrophiles.
  • 1.2K
  • 11 Mar 2022
Topic Review
Role of Endoscopy in Upper Gastrointestinal Cancers
Upper gastrointestinal (GI) malignancy is a leading cause of cancer-related morbidity and mortality. Upper endoscopy has an established role in diagnosing and staging upper GI cancers, screening for pre-malignant lesions, and providing palliation in cases of advanced malignancy. New advances in endoscopic techniques and technology have improved diagnostic accuracy and increased the therapeutic potential of upper endoscopy.
  • 1.2K
  • 16 Jan 2023
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