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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.
  • 789
  • 02 Feb 2021
Topic Review
Cathepsin Proteases and Bcl-2 Proteins
Taken with the growing importance of cathepsin-mediated substrate proteolysis in tumor biology and progression, the focus and emphasis placed on therapeutic design and development is coming into fruition. Underpinning this approach is the invariable progression from the direction of fully characterizing cathepsin protease members and their substrate targets, towards targeting such an interaction with tangible therapeutics. The two groups of such substrates that have gained much attention over the years are the pro- and anti- apoptotic protein intermediates from the extrinsic and intrinsic signaling arms of the apoptosis pathway.
  • 789
  • 08 May 2021
Topic Review
Lynch-like Syndrome
Lynch-like syndrome (LLS) is defined as colorectal cancer cases with microsatellite instability (MSI) and loss of expression of MLH1, MSH2, MSH6, or PMS2 by immunohistochemistry (IHC) in the absence of a germline mutation in these genes that cannot be explained by BRAF mutation or MLH1 hypermethylation.
  • 789
  • 11 Mar 2022
Topic Review
Natural Compounds and Lymphoma
       Lymphoma is a group of blood malignancies that develop from lymphocytes        A natural product is a chemical compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life.         Cancer systems biology encompasses the application of systems biology approaches to cancer research, in order to study the disease as a complex adaptive system with emerging properties at multiple biological scales.
  • 786
  • 29 Oct 2020
Topic Review
The Selected Rare B-Cell Lymphoproliferative Disorders
The updated 4th edition WHO classification of lymphoid malignancies and certain lymphoproliferative disorders (LPD), released in 2016, contains pivotal new terminology and information that is important for both radiologists and oncologists to understand. In spite of these updates, some LPDs included within this update have been rarely discussed in radiology literature. Many of these disorders have distinct clinical and imaging features, overlapping with more common disorders. The purpose of this entry is provide an overview for radiologists regarding certain rare LPDs.
  • 785
  • 03 Dec 2021
Topic Review
Gut and Intratumoral Microbiomes in Tumor Metastasis
Cancer cell dissemination involves invasion, migration, resistance to stressors in the circulation, extravasation, colonization, and other functions responsible for macroscopic metastases. By enhancing invasiveness, motility, and intravasation, the epithelial-to-mesenchymal transition (EMT) process promotes the generation of circulating tumor cells and their collective migration. Preclinical and clinical studies have documented intensive crosstalk between the gut microbiome, host organism, and immune system. According to the findings, polymorphic microbes might play diverse roles in tumorigenesis, cancer progression, and therapy response. Microbial imbalances and changes in the levels of bacterial metabolites and toxins promote cancer progression via EMT and angiogenesis. In contrast, a favorable microbial composition, together with microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), can attenuate the processes of tumor initiation, disease progression, and the formation of distant metastases.
  • 782
  • 15 Apr 2024
Topic Review
Iron Dysregulation in Human Cancer
Iron (Fe) is a trace element that plays essential roles in various biological processes such as DNA synthesis and repair, as well as cellular energy production and oxygen transport, and it is currently widely recognized that iron homeostasis is dysregulated in many cancers. Indeed, several iron homeostasis proteins may be responsible for malignant tumor initiation, proliferation, and for the metastatic spread of tumors. A large number of studies demonstrated the potential clinical value of utilizing these deregulated proteins as prognostic and/or predictive biomarkers of malignancy and/or response to anticancer treatments. Additionally, the iron present in cancer cells and the importance of iron in ferroptosis cell death signaling pathways prompted the development of therapeutic strategies against advanced stage or resistant cancers.
  • 782
  • 05 Jan 2021
Topic Review
HOXA9 Transcription Factor in AML
HOXA9 (Homeobox A9) is a homeotic transcription factor known for more than two decades to be associated with leukemia. The expression of HOXA9 homeoprotein is associated with anterior–posterior patterning during embryonic development, and its expression is then abolished in most adult cells, with the exception of hematopoietic progenitor cells. The oncogenic function of HOXA9 was first assessed in human acute myeloid leukemia (AML), particularly in the mixed-phenotype associated lineage leukemia (MPAL) subtype. HOXA9 expression in AML is associated with aggressiveness and a poor prognosis. Since then, HOXA9 has been involved in other hematopoietic malignancies and an increasing number of solid tumors. Despite this, HOXA9 was for a long time not targeted to treat cancer, mainly since, as a transcription factor, it belongs to a class of protein long considered to be an “undruggable” target; however, things have now evolved.
  • 781
  • 09 Sep 2021
Topic Review
Medulloblastoma
Medulloblastoma is the most prevalent malignant brain tumor in children, while it accounts for only 1–2% of adult brain tumors. Recognized as a biologically heterogeneous disease, the World Health Organization (WHO) considers there to be four molecular subgroups: wingless-activated (WNT), sonic hedgehog-activated (SHH); Group 3; and Group 4. Recently, the picture became more complex when 12 different medulloblastoma subtypes were described, including two WNT subtypes, four SHH subtypes, three group 3 subtypes, and three group 4 subtypes, with each subgroup being characterized by specific mutations, copy number variations, transcriptomic/methylomic profiles, and clinical outcomes. For the SHH subgroup MB, germline or somatic mutations and a copy-number variation are the common drivers that affect critical genes involved in SHH signaling, including PTCH1 (patched 1 homologue), SUFU (suppressor of fused homologue), and SMO (smoothened), among others 
  • 781
  • 29 Sep 2021
Topic Review
Pediatric Mixed-Phenotype Acute Leukemia
Mixed phenotypic acute leukemias (MPAL) are rare hematological malignancies in children, accounting for less than 5% of pediatric acute leukemias. MPAL are heterogeneous and can exhibit cross-lineage myeloid, B-lymphoid, or T-lymphoid antigen expression on a single blast population (biphenotypic) or have distinct single-lineage blast populations (bilineal). Due to phenotypic and genetic diversity, lack of well-defined diagnostic criteria, treatment resistance, and lineage switch, MPAL often present a diagnostic dilemma, and prove difficult to treat.
  • 781
  • 30 Nov 2021
Topic Review
Surgical Anatomy of the Upper Abdomen
Cytoreductive surgery (CRS) is the cornerstone of treating advanced ovarian cancer. Approximately 60–70% of patients with advanced ovarian cancer will have involvement in the upper abdomen or the supracolic compartment of the abdominal cavity. Though the involvement of this region results in poorer survival compared, complete cytoreduction benefits overall survival, making upper-abdominal cytoreduction an essential component of CRS for advanced ovarian cancer. The upper abdomen constitutes several vital organs and large blood vessels draped with the parietal or visceral peritoneum, common sites of disease in ovarian cancer. A surgeon treating advanced ovarian cancer should be well versed in upper-abdominal cytoreduction techniques, including diaphragmatic peritonectomy and diaphragm resection, lesser omentectomy, splenectomy with or without distal pancreatectomy, liver resection, cholecystectomy, and suprarenal retroperitoneal lymphadenectomy. Other procedures such as clearance of the periportal region, Glisson’s capsulectomy, clearance of the superior recess of the lesser sac, and Morrison’s pouch are essential as these regions are often involved in ovarian cancer. 
  • 781
  • 03 Jan 2023
Topic Review
Targeted Agents and Immunotherapy in Sinonasal Cancers
Sinonasal cancers (SNCs) include different tumors of the nasal cavities, maxillary, sphenoidal, ethmoidal, and frontal sinuses. Epithelial SNCs include different histological subtypes: the most common is squamous cell carcinoma (SCC), either keratinizing or non-keratinizing, followed by adenocarcinoma (intestinal-type or non-intestinal type), sinonasal undifferentiated carcinoma (SNUC), sinonasal neuroendocrine carcinoma (SNEC), NUT carcinoma, lymphoepithelial carcinoma, teratocarcinosarcoma, and minor salivary gland tumors.
  • 781
  • 23 Dec 2022
Topic Review
Senolytics for Cancer Therapy
Senolytics represent a group of mechanistically diverse drugs that can eliminate senescent cells, both in tumors and in several aging-related pathologies. Consequently, senolytic use has been proposed as a potential adjuvant approach to improve the response to senescence-inducing conventional and targeted cancer therapies. However, the translation of senolytics to the clinic faces many challenges that need to be addressed by the research community. 
  • 780
  • 09 Mar 2021
Topic Review
Keep Calm and Carry on with Extra Centrosomes
Aberrations in the centrosome number and structure can readily be detected at all stages of tumor progression and are considered hallmarks of cancer. Centrosome anomalies are closely linked to chromosome instability and, therefore, are proposed to be one of the driving events of tumor formation and progression. This concept, first posited by Boveri over 100 years ago, has been an area of interest to cancer researchers.
  • 780
  • 10 Feb 2022
Topic Review
Targeted Therapies for Vestibular Schwannoma
Vestibular schwannoma (VS) is a benign tumor that originates from Schwann cells in the vestibular component. Surgical treatment for VS has gradually declined, especially for small tumors. Gamma knife radiosurgery has become an accepted treatment for VS, with a high rate of tumor control. For neurofibromatosis type 2 (NF2)-associated VS resistant to radiotherapy, vascular endothelial growth factor (VEGF)-A/VEGF receptor (VEGFR)-targeted therapy (e.g., bevacizumab) may become the first-line therapy. A clinical trial using a VEGFR1/2 peptide vaccine was also conducted in patients with progressive NF2-associated schwannomas, which was the first immunotherapeutic approach for NF2 patients. Targeted therapies for the gene product of SH3PXD2A-HTRA1 fusion may be effective for sporadic VS. Several protein kinase inhibitors could be supportive to prevent tumor progression because merlin inhibits signaling by tyrosine receptor kinases and the activation of downstream pathways, including the Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 pathways. Tumor-microenvironment-targeted therapy may be supportive for the mainstays of management. The tumor-associated macrophage is the major component of immunosuppressive cells in schwannomas. 
  • 780
  • 26 May 2022
Topic Review
Role of the Microbiota in Lung Cancer
The microbiota is increasingly recognized as a critical player in cancer onset, progression, and response to chemotherapy treatment. In recent years, several preclinical and clinical studies have evidenced the involvement of microbiota in lung cancer, one of the world’s deadliest cancers. 
  • 780
  • 12 Jul 2022
Topic Review
Advanced Melanoma
Therapeutic options for treating advanced melanoma are progressing rapidly. Until 6 years ago, the regimen for treating advanced melanoma mainly comprised cytotoxic agents such as dacarbazine, and type I interferons. Since 2014, anti-programmed cell death 1 (PD1) antibodies have become recognized as anchor drugs for treating advanced melanoma with or without additional combination drugs such as ipilimumab. In addition, BRAF kinase inhibitors in combination with MEK kinase inhibitors are among the most promising chemotherapeutic regimens for treating advanced BRAF-mutant melanoma, especially in patients with low tumor burden. Since anti-PD1 antibodies are widely applicable for the treatment of both BRAF wild-type and mutated advanced melanomas, several clinical trials for drugs in combination with anti-PD1 antibodies are ongoing. This review focuses on the development of the anti-melanoma therapies available today, and discusses the clinical trials of novel regimens for the treatment of advanced melanoma.
  • 778
  • 03 Nov 2020
Topic Review
Therapies for Treating HER2-Positive Advanced Breast Cancer
The advent of anti-HER2 targeted therapies has dramatically improved the outcome of HER2-positive breast cancer; however, resistance to treatment in the metastatic setting remains a challenge, highlighting the need for novel therapies. The arrival of new treatment options and clinical trials examining the efficacy of novel agents may improve outcomes in the metastatic setting, including in patients with brain metastases. In the first-line setting, the researchers can potentially cure a selected number of patients treated with pertuzumab + trastuzumab + taxane. In the second-line setting, clinical trials show that trastuzumab deruxtecan (T-DXd) is a highly effective option, resulting in a shift from trastuzumab emtansine (T-DM1) as the previous standard of care. Moreover, the researchers now have data for patients with brain metastases to show that tucatinib + trastuzumab + capecitabine can improve survival in this higher-risk group and be an effective regimen for all patients in the third-line setting. Finally, the researchers have a number of effective anti-HER2 therapies that can be used in subsequent lines of therapy to improve patient outcomes. 
  • 778
  • 22 Apr 2022
Topic Review
Pterostilbene in Gastrointestinal Cancer Cells
Pterostilbene (PTE) is a natural sterbenoid contained in blueberries that has an antioxidant effect. In contrast, PTE also generates oxidative stress in cancer cells and provides an antitumor effect.
  • 777
  • 30 Dec 2020
Topic Review
Tumour Hypoxia-Mediated Immunosuppression
The magnitude of the host immune response can be regulated by either stimulatory or inhibitory immune checkpoint molecules. Receptor-ligand binding between inhibitory molecules is often exploited by tumours to suppress anti-tumour immune responses. Immune checkpoint inhibitors that block these inhibitory interactions can relieve T-cells from negative regulation, and have yielded remarkable activity in the clinic. 
  • 777
  • 29 Jun 2021
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