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Topic Review
Breast Cancer Stem Cells
Breast cancer is a highly heterogeneous and phenotypically diverse group of diseases, which require different selection of treatments. Accurately being able to distinguish between the various subtypes of breast cancer is vital as they have different prognoses and responses to therapy. Gene expression studies have identified six distinct molecular subtypes for breast cancer, which characterize distinct physiological presentation, gene expression profile, prognosis and clinical outcomes. These subtypes are classified according to the presence or absence of hormone (estrogen (ER) or progesterone (PR)) receptors (HR+/HR-) and human epidermal growth factor receptor 2 (HER2+/HER2-). Luminal A (HR+/HER2-) represents a slow-growing and less aggressive subtype, while luminal B (HR+/HER2+) seems to be more aggressive than luminal A. HER2-positive (HR-/HER2+) breast cancers, which express excess HER2 and do not express hormone receptors, grow and spread more aggressively than other breast cancers and are correlated with poorer prognosis than ER+ breast cancers. 
  • 641
  • 04 Aug 2021
Topic Review
Wnt Signaling in Keratinocyte Carcinomas
The skin functions as a barrier between the organism and the surrounding environment. Direct exposure to external stimuli and the accumulation of genetic mutations may lead to abnormal cell growth, irreversible tissue damage and potentially favor skin malignancy. Skin homeostasis is coordinated by an intricate signaling network, and its dysregulation has been implicated in the development of skin cancers. Wnt signaling is one such regulatory pathway orchestrating skin development, homeostasis, and stem cell activation. Aberrant regulation of Wnt signaling cascades not only gives rise to tumor initiation, progression and invasion, but also maintains cancer stem cells which contribute to tumor recurrence.
  • 641
  • 22 Sep 2021
Topic Review
Natural Blockers of PD-1/PD-L1 Interaction
The limited treatment options for triple-negative breast cancer with brain metastasis (TNBC-BM) have left the door of further drug development for these patients wide open. Although immunotherapy via monoclonal antibodies has shown some promising results in several cancers including TNBC, it cannot be considered the most effective treatment for brain metastasis. This is due to the protective role of the blood–brain barrier (BBB) which limits the entrance of most drugs, especially the bulky ones such as antibodies, to the brain. For a drug to traverse the BBB via passive diffusion, various physicochemical properties should be considered. 
  • 641
  • 11 Jan 2023
Topic Review
Immunotherapy for Glioblastoma
       Glioblastoma (GBM) is the deadliest and most aggressive neuroepithelial cancer of the central nervous system (CNS) with an abysmal median survival of 14.6-month despite the multiple forms of intervention. In the United States, the total annual incidence rate of glioma has been ~6 cases per 100,000 individuals, of which GBM accounts for about 50% of the cases, with a higher predominance in males. Clinical studies have indicated that most of the GBM patients present an intact blood–brain barrier (BBB) for certain brain regions, capable of blocking the delivery of agents to cancer sites. The BBB is considered to prevent diffusion of 98% of small-molecule and 100% of large-molecule agents into the brain from blood circulation. Given the aggressive and heterogeneous nature of GBM and the blocking capability of BBB, a very limited number of medications for patients with GBM is available in clinics. In addition, due to the existence of other cellular and extracellular barriers, as well as the development of drug resistance over the treatment course, the efficacy of many current therapeutic approaches has been compromised.        Currently available standards of care for GBM include maximal tumor resection followed by radiotherapy, chemotherapy, and corticosteroids, all of which have immune suppressive characteristics. Unfortunately, complete surgical removal of the whole tumor is almost impossible due to their diffusive characteristics into normal brain tissue. Some reports indicated that ~65% of the post-surgery cases still showed residual tumor cells, which eventually contributed to a high relapse rate of GBM . Therefore, GBM patients may undergo repeated surgical resection, radiotherapy, chemotherapy, or additional bevacizumab treatment. Eventually, most of the patients suffering from GBM will relapse despite an ample set of interventional approaches. According to the data from Surveillance and Epidemiology, the median overall survival (OS) of GBM patients was normally less than 2 years from the time of first progression or relapse. An international phase III randomized trial, conducted by the European Organization for Research and Treatment of Cancer/National Cancer Institute of Canada (EORTC/NCIC), has shown that the median OS of GBM patients who received radiotherapy and Temozolomide therapy remains poor (14.6 months). Moreover, Grossman and colleagues found that the utilization of systemic chemotherapy and hyperfractionated radiation therapy with corticosteroids is likely to disable immune activity. Immune-suppressive characteristics, high toxicity, and lower OS of traditional care made a considerable number of GBM patients (~50%) not accept any second-line of anti-tumor treatment. In addition, there is no evidence that traditional intervention can significantly impact the OS rate under a recurrence setting. Accordingly, given the poor prognosis and limited therapy regimens for patients affected by GBM, there is an urgent need to develop novel therapeutic approaches.
  • 640
  • 25 Aug 2020
Topic Review
Allogeneic Hematopoietic Cell Transplantation
Allogeneic hematopoietic cell transplantation (alloHCT) represents a treatment option for multiple myeloma (MM) patients. As shown in several studies, alloHCT is highly effective, but it is hampered by a high toxicity, mainly related to the graft-versus-host disease (GVHD), a complex immunological reaction ascribable to the donor’s immune system. The morbidity and mortality associated with GVHD can weaken the benefits of this procedure. On the other side, the high therapeutic potential of alloHCT is also related to the donor’s immune system, through immunological activity known as the graft-versus-myeloma effect.
  • 640
  • 09 Nov 2020
Topic Review
Gastric Carcinoma and Pre-neoplastic Lesions
Gastric carcinoma (GC) represents one of the most common and most lethal malignancies worldwide. The histopathological characterization of GC precursor lesions has provided great knowledge about gastric carcinogenesis, with the consequent introduction of effective strategies of primary and secondary prevention. In recent years, a large amount of data about the molecular events in GC development is emerging, flanking the histomorphological descriptions. 
  • 640
  • 24 Sep 2021
Topic Review
Gal-9/TIM-3 Immune Checkpoint with α-Lactose
The disaccharide lactose is an excipient commonly used in pharmaceutical products. The two anomers, α- and β-lactose (α-L/β-L), differ by the orientation of the C-1 hydroxyl group on the glucose unit. In aqueous solution, a mutarotation process leads to an equilibrium of about 40% α-L and 60% β-L at room temperature.
  • 640
  • 04 Jan 2022
Topic Review
Salt-Tolerant Plants for Cancer Prevention and Treatment
Halophytes and xerophytes, plants with adequate tolerance to high salinity with strong ability to survive in drought ecosystem, have been recognized for their nutritional and medicinal values owing to their comparatively higher productions of secondary metabolites, primarily the phenolics, and the flavonoids, as compared to the normal vegetation in other climatic regions. Given the consistent increases in desertification around the world, which are associated with increasing salinity, high temperature, and water scarcity, the survival of halophytes due to their secondary metabolic contents has prioritized these plant species, which have now become increasingly important for environmental protection, land reclamation, and food and animal-feed security, with their primary utility in traditional societies as sources of drugs. On the medicinal herbs front, because the fight against cancer is still ongoing, there is an urgent need for development of more efficient, safe, and novel chemotherapeutic agents, than those currently available.
  • 640
  • 16 Mar 2023
Topic Review
Cancer Associated Fibroblasts
Cancer-associated fibroblasts are important players of the tumour microenvironment. They influence numerous processes during tumour development and progression, including the response of cancer cells to treatment. As a consequence, this cell type has emerged has a prominent target in anti-cancer therapy.
  • 640
  • 28 Jul 2021
Topic Review
Neoadjuvant treatment in breast cancer
Neoadjuvant Chemotherapy (NAC) in Breast Cancer (BC) has proved useful for the reduction in tumor burden prior to surgery, allowing for a more extensive breast preservation and the eradication of subjacent micrometastases. However, the impact on prognosis is highly dependent on the establishment of Pathological Complete Response (pCR), in particular for Triple Negative (TN) and Hormonal Receptor negative/Human Epidermal growth factor Receptor 2 positive (HR−/HER2+) subtypes. Several pCR predictors, such as PAM50, Integrative Cluster (IntClust), mutations in PI3KCA, or the Trastuzumab Risk model (TRAR), are useful molecular tools for estimating response to treatment and are prognostic. Major evolution events during BC NAC that feature the Residual Disease (RD) are the loss of HR and HER2, which are prognostic of bad outcome, and stemness and immune depletion-related gene expression aberrations. This dynamic nature of the determinants of response to BC NAC, together with the extensive heterogeneity of BC, raises the need to discern the individual and subtype-specific determinants of resistance. Moreover, refining the current approaches for a comprehensive monitoring of tumor evolution during treatment, RD, and eventual recurrences is essential for identifying new actionable alterations and the integral best management of the disease.breast cancer; neoadjuvant chemotherapy; pathological complete response; predictive markers; residual diseasebreast cancer; neoadjuvant chemotherapy; pathological complete response; predictive markers; residual disease
  • 639
  • 08 Aug 2020
Topic Review
P53, micro-RNA and Cathepsin Protease
As the direct regulatory role of p53 and some of its isoform proteins are becoming established in modulating gene expression in cancer research, another aspect of this mode of gene regulation that has captured significant interest over the years is the mechanistic interplay between p53 and micro-RNA transcriptional regulation. The input of this into modulating gene expression for some of the cathepsin family members has been viewed as carrying noticeable importance based on their biological effects during normal cellular homeostasis and cancer progression. 
  • 639
  • 19 Dec 2020
Topic Review
5-Aminolevulinic Acid in Gliomas
5-aminolevulinic acid (5-ALA) is a porphyrin precursor in the heme synthesis pathway. When supplied exogenously, certain cancers consume 5-ALA and convert it to the fluorogenic metabolite protoporphyrin IX (PpIX), causing tumor-specific tissue fluorescence. Preoperative administration of 5-ALA is used to aid neurosurgical resection of high-grade gliomas such as glioblastoma, allowing for increased extent of resection and progression free survival for these patients. Targeting the heme synthesis pathway and understanding its dysregulation in malignant tissues could aid the development of adjunct therapies to increase intraoperative fluorescence after 5-ALA treatment
  • 639
  • 14 Apr 2021
Topic Review
Application of Plasma Proteome Signature in Breast Cancer
The prognostic impact of plasma protein biomarkers in breast cancer patients treated with neoadjuvant chemotherapy (NCT) was evaluated using a proteomics approach. Three biomarkers were identified among differentially expressed proteins. The plasma concentration of APOC3 was higher in the pathological complete response (pCR) group, whereas MBL2, ENG, and P4HB were upregulated in the non-pCR group.
  • 639
  • 28 Dec 2021
Topic Review
Functional Decline in the Older Cancer Patient
A decline in functional status, an individual’s ability to perform the normal activities required to maintain adequate health and meet basic needs, is part of normal ageing. Functional decline, however, appears to be accelerated in older patients with cancer. Such decline can occur as a result of a cancer itself, cancer treatment-related factors, or a combination of the two. The accelerated decline in function seen in older patients with cancer can be slowed, or even partly mitigated through routine assessments of functional status and timely interventions where appropriate. This is particularly important given the link between functional decline and impaired quality of life, increased mortality, comorbidity burden, and carer dependency.
  • 639
  • 11 Apr 2022
Topic Review
Obesity and Immunometabolic Changes in Adipose Tissue
White adipose tissue (WAT) represents an endocrinologically and immunologically active tissue whose primary role is energy storage and homeostasis. Breast WAT is involved in the secretion of hormones and proinflammatory molecules that are associated with breast cancer development and progression.
  • 639
  • 12 May 2023
Topic Review
Potentiality of Nanoenzymes for Cancer Treatment
Nanozyme synthesis is an innovative technology since it connects nanoparticles with biological activities and framework. Various assays have been implemented for the enzymes of proteins that also implement nanozymes, which could also have the potential for performing the catalysis of similar substrates. Due to such different functions of nanozymes, they are used for the treatment of the environment, biosensing, agents that act against microbes, cytoprotection of different cell biomolecules with management, diagnosis of diseases, etc..
  • 638
  • 22 Oct 2021
Topic Review
Atypical Teratoid/Rhabdoid Tumor in Taiwan
Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, highly aggressive embryonal brain tumor most commonly presenting in young children. Older age, supratentorial site, and treatment with radiotherapy, chemotherapy, or both were significantly associated with better survival of patients with AT/RT in Taiwan. 
  • 638
  • 08 Feb 2022
Topic Review
Oncofertility in Patients with Breast Cancer
Breast cancer is the most common malignancy occurring in young women.  Improving the prognosis of breast cancer patients is of utmost importance in terms of increasing survival rates. Modern medicine has therefore prioritized better quality of life for patients, even after the disease, through a better management of the potential long-term side effects induced by anticancer treatments. Fertility preservation and family planning are therefore crucial issues to be addressed in all cancer patients of reproductive age. Along those lines, a new branch of medicine with distinct multidisciplinary characteristics has developed over the years: oncofertility.
  • 638
  • 06 Apr 2022
Topic Review
Mycobacteria and Cancer
Although the therapeutic effect of mycobacteria as antitumor agents has been known for decades, recent epidemiological and experimental studies have revealed that mycobacterium-related chronic inflammation may be a possible mechanism of cancer pathogenesis. Mycobacterium tuberculosis and non-tuberculous Mycobacterium avium complex infections have been implicated as potentially contributing to the etiology of lung cancer, whereas Mycobacterium ulcerans has been correlated with skin carcinogenesis. The risk of tumor development with chronic mycobacterial infections is thought to be a result of many host effector mechanisms acting at different stages of oncogenesis.
  • 637
  • 28 Sep 2021
Topic Review
Biliary Tract Cancer Management
Biliary tract cancers (BTC) comprise a group of malignancies originating in the epithelium of the biliary tract. These include cholangiocarcinoma (CCA) and gallbladder carcinoma (GBC). Intrahepatic cholangiocarcinoma or iCCA refers to tumors proximal to the second-order ducts, while extrahepatic cholangiocarcinoma or eCCA refers to tumors arising more distally (perihilar CCA, between second-order ducts and cystic duct and distal CCA, distal to cystic duct). Perihilar CCA represents 50% of the total CCAs, with distal lesions comprising 40% and the final 10% being intrahepatic. BTC are often diagnosed at advanced stages and have a grave outcome due to limited systemic options. Gemcitabine and cisplatin combination (GC) has been the first-line standard for more than a decade. Second-line chemotherapy (CT) options are limited. Targeted therapy or TT (fibroblast growth factor 2 inhibitors or FGFR2, isocitrate dehydrogenase 1 or IDH-1, and neurotrophic tyrosine receptor kinase or NTRK gene fusions inhibitors) have had reasonable success, but <5% of total BTC patients are eligible for them. The use of immune checkpoint inhibitors (ICI) such as pembrolizumab is restricted to microsatellite instability high (MSI-H) patients in the first line. The success of the TOPAZ-1 trial (GC plus durvalumab) is promising, with numerous trials underway that might soon bring targeted therapy (pemigatinib and infrigatinib) and ICI combinations (with CT or TT in microsatellite stable cancers) in the first line.
  • 637
  • 20 May 2022
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