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Topic Review
Serrated Pathway in Colorectal Cancer
Colorectal cancer (CRC) is a leading cause of cancer death worldwide. It includes different subtypes that differ in their clinical and prognostic features. In the past decade, in addition to the conventional adenoma-carcinoma model, an alternative multistep mechanism of carcinogenesis, namely the “serrated pathway”, has been described. Approximately, 15 to 30% of all CRCs arise from neoplastic serrated polyps, a heterogeneous group of lesions that are histologically classified into three morphologic categories: hyperplastic polyps, sessile serrated adenomas/polyps, and the traditional serrated adenomas/polyps. Serrated polyps are characterized by genetic (BRAF or KRAS mutations) and epigenetic (CpG island methylator phenotype (CIMP)) alterations that cooperate to initiate and drive malignant transformation from normal colon mucosa to polyps, and then to CRC. The high heterogeneity of the serrated lesions renders their diagnostic and pathological interpretation difficult. 
  • 575
  • 10 Sep 2021
Topic Review
Ion Transport System in Cervical Cancer
Cervical cancer is a significant gynecological cancer and causes cancer-related deaths worldwide. Human papillomavirus (HPV) is implicated in the etiology of cervical malignancy. However, much evidence indicates that HPV infection is a necessary but not sufficient cause in cervical carcinogenesis. Therefore, the cellular pathophysiology of cervical cancer is worthy of study. 
  • 575
  • 06 Jan 2022
Topic Review
Precision Medicine in Cholangiocarcinoma
Cholangiocarcinoma (CCA), or biliary tract cancer, has a poor prognosis. The median survival time among patients with CCA is under 2 years from diagnosis, and the global 5-year survival rate is only 10%. First-line therapy with chemotherapeutic agents, gemcitabine plus cisplatin, has traditionally been used to treat unresectable advanced CCA. Precision medicine has become a mainstream cancer treatment due to innovative next-generation sequencing technology. 
  • 575
  • 14 Jun 2022
Topic Review
GPR56 a Novel Immune Checkpoint on Tumor-Infiltrating Lymphocytes
Despite the clinical efficacy of so-called immune checkpoint inhibitors (ICIs) in various cancers, some cancer types, including epithelial ovarian cancer (EOC), do not effectively respond to current therapeutics. Thus, the identification of new immune checkpoints that regulate T cell immunity remains of great interest. One as yet largely uninvestigated checkpoint of potential interest is the G protein-coupled receptor 56 (GPR56), which belongs to the adhesion GPCR family. Here in this study,   it was identified that GPR56 is expressed on tumor infiltrating lymphocytes (TILs) and investigated its role as a potential immune checkpoint within the context of cancer. Based on the investigated data, GPR56 indeed appears to function as an immune checkpoint in TILs and may thus provide a novel immunotherapeutic target for the reactivation of tumor-infiltrating and tumor-reactive lymphocytes.
  • 575
  • 22 Nov 2022
Topic Review
Development of the Colorectal Cancer Obstructive Mechanism
The spontaneous evolution of colorectal cancer is always burdened by complications. The most common complication is low bowel obstruction, found in approximately 20% of the cases of colorectal cancer, and it can occur either relatively abruptly, or is preceded by initially discrete premonitory symptoms, non-specific (until advanced evolutionary stages) and generally neglected or incorrectly interpreted. Success in the complex treatment of a low neoplastic obstruction is conditioned by a complete diagnosis, adequate pre-operative preparation, a surgical act adapted to the case (in one, two or three successive stages), and dynamic postoperative care. The moment of surgery should be chosen with great care and is the result of the experience of the anesthetic-surgical team. The operative act must be adapted to the case and has as its main objective the resolution of intestinal obstruction and only in a secondary way the resolution of the generating disease.
  • 575
  • 29 May 2023
Topic Review
Key Heterocyclic Anti-Angiogenic Leads
Pathological angiogenesis is a hallmark of cancer; accordingly, a number of anticancer FDA-approved drugs act by inhibiting angiogenesis via different mechanisms. However, the development process of the most potent anti-angiogenics has met various hurdles including redundancy, multiplicity, and development of compensatory mechanisms by which blood vessels are remodeled. Moreover, identification of broad-spectrum anti-angiogenesis targets is proved to be required to enhance the efficacy of the anti-angiogenesis drugs. In this perspective, a proper understanding of the structure activity relationship (SAR) of the recent anti-angiogenics is required. Various anti-angiogenic classes have been developed over the years; among them, the heterocyclic organic compounds come to the fore as the most promising, with several drugs approved by the FDA.
  • 574
  • 24 Feb 2021
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. 
  • 574
  • 20 Oct 2022
Topic Review
Targeting Mononuclear Phagocyte Receptors
Inflammatory cells are major players in the onset of cancer. The degree of inflammation and type of inflammatory cells in the tumor microenvironment (TME) are responsible for tilting the balance between tumor progression and regression. Cancer-related inflammation has also been shown to influence the efficacy of conventional therapy. Mononuclear phagocytes (MPs) represent a major component of the inflammatory circuit that promotes tumor progression. Despite their potential to activate immunosurveillance and exert anti-tumor responses, MPs are subverted by the tumor to support its growth, immune evasion, and spread. MP responses in the TME are dictated by a network of stimuli integrated through the cross-talk between activatory and inhibitory receptors. Alterations in receptor expression/signaling can create excessive inflammation and, when chronic, promote tumorigenesis. Research advances have led to the development of new therapeutic strategies aimed at receptor targeting to induce a tumor-infiltrating MP switch from a cancer-supportive toward an anti-tumor phenotype, demonstrating efficacy in different human cancers.
  • 573
  • 09 Oct 2020
Topic Review
Breast Cancer-Related Lymphedema
Breast cancer-related lymphedema (BCRL) represents a global healthcare issue affecting the emotional and life quality of breast cancer survivors significantly. The clinical presentation is characterized by swelling of the affected upper limb, that may be accompanied by atrophic skin findings, pain and recurrent cellulitis. Cardinal principles of lymphedema management are the use of complex decongestive therapy and patient education. Recently, new microsurgery procedures have been reported with interesting results, bringing in a new opportunity to care postmastectomy lymphedema. However, many aspects of the disease are still debated in the medical community, including clinical examination, imaging techniques, patient selection and proper treatment.
  • 573
  • 23 Jun 2021
Topic Review
Anal Squamous Cell Carcinoma
Anal squamous cell carcinoma (ASCC) is a rare malignancy, with most cases associated with human papilloma virus and an increased incidence in immunocompromised patients.
  • 573
  • 23 Jun 2021
Topic Review
TP53 in Germ Cell Tumours
The cure rate of germ cell tumours (GCTs) has significantly increased from the late 1970s since the introduction of cisplatin-based therapy. The exquisite cisplatin sensitivity has been mainly explained by the over-expression in GCTs of wild-type TP53 protein and the lack of TP53 somatic mutations; however, several other mechanisms seem to be involved, many of which remain still elusive. The findings about the role of TP53 in platinum-sensitivity and resistance, as well as the reported evidence of second cancers (SCs) in GCT patients treated only with surgery, suggesting a spectrum of cancer predisposing syndromes, highlight the need for a deepened understanding of the role of TP53 in GCTs. 
  • 573
  • 27 Jul 2021
Topic Review
Primary Central Nervous System Lymphoma
Primary central nervous system lymphoma (PCNSL) is a highly aggressive non-Hodgkin lymphoma confined to the central nervous system (CNS) and mainly affects elderly patients.
  • 573
  • 30 Aug 2021
Topic Review
Cervical Carcinoma
Cervical cancer is one of the most common types of carcinomas causing morbidity and mortality in women in all countries of the world. At the moment, the oncology, oncobiology, and oncomorphology of cervical cancer are characterized by the accumulation of new information; various molecular biological, genetic, and immunohistochemical methods of investigation of the mechanisms of cervical carcinogenesis are tested and applied; targeted antitumour drugs and diagnostic, prognostic, and predictive biomarkers are being searched for. Many issues of the etiopathogenesis of cervical cancer have not been sufficiently studied, and the role of many biomarkers characterizing various stages of cervical carcinogenesis remains unclear.
  • 573
  • 13 Dec 2021
Topic Review
Revisiting Hepatic Artery Infusion Chemotherapy
Hepatic artery infusion chemotherapy (HAIC) is a well-established and common treatment for advanced hepatocellular carcinoma (HCC), particularly in East Asia. However, HAIC is not recognized internationally. Although several trials have demonstrated the safety and efficacy of HAIC, evidence corroborating its overall survival (OS) benefits compared with standard treatments is insufficient. Nevertheless, HAIC may provide prominent benefits in selected patients such as patients with portal vein thrombosis or high intrahepatic tumor burden. Moreover, HAIC has been combined with several therapeutic agents and modalities, including interferon-alpha, multikinase inhibitors, radiation therapy, and immunotherapy, to augment its treatment efficacy. Most of these combinations appeared to increase overall response rates compared with HAIC alone, but results regarding OS are inconclusive. Two prospective randomized controlled trials comparing HAIC plus sorafenib with sorafenib alone have reported conflicting results, necessitating further research. As immunotherapy-based combinations became the mainstream treatments for advanced HCC, HAIC plus immunotherapy-based treatments also showed encouraging preliminary results. The trials of HAIC were heterogeneous in terms of patient selection, chemotherapy regimens and doses, HAIC combination agent selections, and HAIC technical protocols. These heterogeneities may contribute to differences in treatment efficacy, thus increasing the difficulty of interpreting trial results.
  • 573
  • 29 Mar 2022
Topic Review
Long-Term Management of Advanced Basal Cell Carcinoma
The first-line therapy for locally advanced basal cell carcinoma (laBCC) is Hedgehog pathway inhibitors (HHIs), as they achieve good efficacy and duration of response. However, toxicity in the course of long-term treatment may lead to a decrease in the quality of life, and consequently to interruption or even discontinuation of therapy. As HHI therapy is a balancing act between effectiveness, adverse events, quality of life, and adherence, numerous successful treatment strategies have evolved, such as dose reduction and dose interruptions with on-off treatment schedules or interruptions with re-challenge after progression. As a small percentage of patients show primary or acquired resistance to HHIs, the inhibition of programmed cell death protein 1 (PD-1) has been approved as a second-line therapy, which may also be accompanied by immune-related toxicities and non-response. Thus, optimization of current treatment schedules, novel agents, and combination strategies are urgently needed for laBCC. 
  • 573
  • 01 Dec 2022
Topic Review
Temperature-Sensitive Nanomaterials therapeutic potentials
Nanotechnology has great capability in formulation, reduction of side effects, and enhancing pharmacokinetics of chemotherapeutics by designing stable or long circulating nano-carriers. However, effective drug delivery at the cellular level by means of such carriers is still unsatisfactory. One promising approach is using spatiotemporal drug release by means of nanoparticles with the capacity for content release triggered by internal or external stimuli. Among different stimuli, interests for application of external heat, hyperthermia, is growing. Advanced technology, ease of application and most importantly high level of control over applied heat, and as a result triggered release, and the adjuvant effect of hyperthermia in enhancing therapeutic response of chemotherapeutics, i.e., thermochemotherapy, make hyperthermia a great stimulus for triggered drug release. Therefore, a variety of temperature sensitive nano-carriers, lipid or/and polymeric based, have been fabricated and studied. Importantly, in order to achieve an efficient therapeutic outcome, and taking the advantages of thermochemotherapy into consideration, release characteristics from nano-carriers should fit with applicable clinical thermal setting. Here we introduce and discuss the application of the three most studied temperature sensitive nanoparticles with emphasis on release behavior and its importance regarding applicability and therapeutic potentials.
  • 572
  • 07 Dec 2020
Topic Review
ABHD11 Antisense RNA 1
ABHD11-AS1 is an RNA gene known as long intergenic non-protein coding RNA 35 (LINC00035) and Williams–Beuren syndrome chromosome region 26 (WBSCR26), located at 7q11.23.
  • 572
  • 14 Mar 2022
Topic Review
Markers in Diagnostics and Classification of Breast Cancer
Breast cancer (BC)is etiologically, histopathologically and genetically a heterogeneous disease with both hereditary predispositions and non-hereditary factors. This is certainly true for BC as it refers to mammary carcinoma from ductal or lobular cells in the mammary epithelial tissue. Only a minor portion are sarcomas transformed from connective tissue and vessels. Malignant transformation in BC is the product of accumulations of consecutive mutations in critical regions of the genome that are normally involved in control of cell growth and division, DNA repair and programmed cell death. These mutations are partly inherited but mostly spontaneous. Contribution of genetic factors in BC has been indicated by familial occurrence which is estimated as 5–10% of all cases. High-penetrance genes which are linked with inherited BC susceptibility include BRCA1 and BRCA2, and more rarely TP53, PTEN, CDH1 and SKT11. Heterozygotic mutations in DNA repair genes BRCA1 (locus Ch17q21.31) or BRCA2 (Ch13q13.1) are the most common inherited conditions associated with BC. Absolute risk of BC for BRCA1 mutations reads ~50–65% in females and ~1% in males, while in BRCA2 mutations female risk ranges from 40% to 55% and reaches up to 9% in males. Familiar susceptibility to BC is also associated with mutations of lower penetrance genes as ATM (Ch11q22.3), PALB2 (Ch16p12.2) and CHEK2 (Ch22q12.1). Mutation in the androgen receptor gene (AR) has been found in cases of male BC. Susceptibility to sporadic BC cases can be linked with many more genes: e.g., sporadic invasive ductal variant of BC and lobular BC are associated with somatic mutation of genes RAD54L (Ch1p34.1) and CDH1 (Ch16q22.1), respectively. Other genes candidates associated with sporadic BC include: TP53 (Ch17p13.1), SLC22A1 (Ch11p15.4), PIK3CA (Ch3q26.32), ESR1 (Ch6q25.1-q25.2), RB1CC1 (Ch8q11.23), KRAS (12p12.1), AKT1 (14q32.33), RB1 (Ch13q14.2), PPM1D (Ch17q23.2), MYC (Ch8q24.21), FGFR1 and eventually ERBB2 (Ch17q12), CCND1 (Ch11q13.3), GATA3 (Ch10p14), MAP3K1 (Ch5q11.2) in certain lineages.
  • 572
  • 22 Nov 2022
Topic Review
Current Landscape of HER2-Targeted ADCs
Human epidermal growth factor receptor 2 (HER2) tyrosine kinase is overexpressed in 20% of breast cancers and associated with a less favorable prognosis compared to HER2-negative disease.
  • 572
  • 21 Feb 2024
Topic Review
Triple-Negative Breast Cancer
Triple negative breast cancer (TNBC) is a heterogeneous tumor characterized by early recurrence, high invasion, and poor prognosis. Currently, its treatment includes chemotherapy, which shows a suboptimal efficacy. However, with the increasing studies on TNBC subtypes and tumor molecular biology, great progress has been made in targeted therapy for TNBC. The new developments in the treatment of breast cancer include targeted therapy, which has the advantages of accurate positioning, high efficiency, and low toxicity, as compared to surgery, radiotherapy, and chemotherapy. Given its importance as cancer treatment, we review the latest research on the subtypes of TNBC and relevant targeted therapies. 
  • 571
  • 30 Jun 2021
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