scholarly journals Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2803
Author(s):  
Carolin Czauderna ◽  
Martha M. Kirstein ◽  
Hauke C. Tews ◽  
Arndt Vogel ◽  
Jens U. Marquardt
Keyword(s):  
Clinical Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Treatment Modalities ◽  
Precision Oncology ◽  
Recurrence Rates ◽  
Isocitrate Dehydrogenase 1 ◽  
Liver Cancers

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.

scholarly journals Cancer-Associated Fibroblasts in Breast Cancer Treatment Response and Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3146
Author(s):  
Patricia Fernández-Nogueira ◽  
Gemma Fuster ◽  
Álvaro Gutierrez-Uzquiza ◽  
Pere Gascón ◽  
Neus Carbó ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptors ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Cancer Associated Fibroblasts ◽  
Luminal A ◽  
Luminal B ◽  
Number Of Patients ◽  
Current Therapies

Breast cancer (BrCa) is the leading cause of death among women worldwide, with about one million new cases diagnosed each year. In spite of the improvements in diagnosis, early detection and treatment, there is still a high incidence of mortality and failure to respond to current therapies. With the use of several well-established biomarkers, such as hormone receptors and human epidermal growth factor receptor-2 (HER2), as well as genetic analysis, BrCa patients can be categorized into multiple subgroups: Luminal A, Luminal B, HER2-enriched, and Basal-like, with specific treatment strategies. Although chemotherapy and targeted therapies have greatly improved the survival of patients with BrCa, there is still a large number of patients who relapse or who fail to respond. The role of the tumor microenvironment in BrCa progression is becoming increasingly understood. Cancer-associated fibroblasts (CAFs) are the principal population of stromal cells in breast tumors. In this review, we discuss the current understanding of CAFs’ role in altering the tumor response to therapeutic agents as well as in fostering metastasis in BrCa. In addition, we also review the available CAFs-directed molecular therapies and their potential implications for BrCa management.

Dupuytren's Disease: An Outcomes-Focused Update

2021 ◽  
Author(s):  
Yasser H. Almadani ◽  
Joshua Vorstenbosch ◽  
Johnny Ionut Efanov ◽  
Liqin Xu
Keyword(s):  
Patient Education ◽  
Genetic Predisposition ◽  
Treatment Options ◽  
Clinical Treatment ◽  
Dupuytren’S Disease ◽  
Treatment Modalities ◽  
Recurrence Rates ◽  
Dupuytren's Disease ◽  
Associated Factor ◽  
Informed Decisions

AbstractDupuytren's disease (DD) remains a common fibroproliferative condition with significant sequelae and impact on patient's lives. The etiology of DD is poorly understood, and genetic predisposition is thought to be a strongly associated factor. Despite remarkable strides in improving our molecular understanding of DD, clinical treatment options have not yet overcome the frequently encountered challenge of recurrence. Recurrence rates continue to shape the prognosis of this fibrotic condition. In this outcomes-focused article, the various treatment modalities are reviewed. This further emphasizes the importance of patient education and providing them with the information to make informed decisions about their treatment.

scholarly journals Biliary Tract Cancers: Molecular Heterogeneity and New Treatment Options

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3370
Author(s):  
Nicola Personeni ◽  
Ana Lleo ◽  
Tiziana Pressiani ◽  
Francesca Colapietro ◽  
Mark Robert Openshaw ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Advanced Disease ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Resistance Mechanisms ◽  
Anatomical Location ◽  
Molecular Heterogeneity ◽  
Isocitrate Dehydrogenase 1 ◽  
Tract Cancer

Most patients with biliary tract cancer (BTC) are diagnosed with advanced disease, relapse rates are high in those undergoing surgery and prognosis remains poor, while the incidence is increasing. Treatment options are limited, and chemotherapy is still the standard of care in both adjuvant and advanced disease setting. In recent years, different subtypes of BTC have been defined depending on the anatomical location and genetic and/or epigenetic aberrations. Especially for intrahepatic cholangiocarcinoma (iCCA) novel therapeutic targets have been identified, including fibroblast growth factor receptor 2 gene fusions and isocitrate dehydrogenase 1 and 2 mutations, with molecularly targeted agents having shown evidence of activity in this subgroup of patients. Additionally, other pathways are being evaluated in both iCCA and other subtypes of BTC, alongside targeting of the immune microenvironment. The growing knowledge of BTC biology and molecular heterogeneity has paved the way for the development of new therapeutic approaches that will completely change the treatment paradigm for this disease in the near future. This review provides an overview of the molecular heterogeneity of BTC and summarizes new targets and emerging therapies in development. We also discuss resistance mechanisms, open issues, and future perspectives in the management of BTC.

Dermatological toxicities of panitumumab in the treatment of patients with metastatic colorectal cancer (mCRC) from three clinical studies

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14551-14551 ◽  
Author(s):  
D. A. Drelich ◽  
L. Rose ◽  
M. Ramirez ◽  
M. Jacobs ◽  
E. Mitchell
Keyword(s):  
African American ◽  
Clinical Studies ◽  
Human Monoclonal Antibody ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Skin Toxicity ◽  
Metastatic Potential ◽  
Median Number ◽  
Egfr Expression

14551 Introduction: Epidermal growth factor receptor (EGFr) expression in CRC is associated with metastatic potential and poor prognosis. Panitumumab, a fully human monoclonal antibody against EGFr, was approved for the treatment of patients with refractory mCRC. The main side effects of panitumumab include dermatological manifestations that have been termed “rash”. However, classification of the dermatological manifestations has not been clearly described. Methods: We summarized the dermatological manifestations of 19 patients from 3 clinical studies investigating the the safety and efficacy of panitumumab monotherapy in mCRC in a single institution. Two of these studies were open lable, phase 2 in design which enrolled patients with documented disease progression (PD) during or after adequate doses of fluoropyrimidine, irinotecan, and oxaliplatin chemotherapy. In the other panitumumab was given in combination with irinotecan or oxaliplatin with bevacuzumab, 5FU, and leucovorin. Pts received panitumumab at 6mg/kg Q2W until PD or intolerability. Skin assessments were made q2w. Results: Five patients were men (26%) and 14 (73%) women; 12 were Caucasian (63%) and 7 (36%) African American. The median age was 53 (Range 38–80). Tumor response, disease control, and skin manifestations did not correlate with tumor EGFr levels as assessed by immunohisxtochemistry (Dako EGFR pharmDxtm). No enhancement of skin toxicity was observed when panitumumab was combined with chemotherapy. The median number of cycles received was 11 (Range 3–20). All pts experienced erythema; 17 macular/papular; 13 pustular; 18 acneiform rash; 15 pruritis; 3 honey crusting; 15 dry/flaking; 11 paronychia; 9 hirsuitism; 9 trichomegaly; and all 7 African American patients had significant hyperpigmentation. Photograph illustrations of each category and severity will be presented. Conclusion: Rash associated with panitumumab is common and can be classified according to the clinical dermatological manifestations; specific treatment strategies should be developed and evaluated accordingly. This is the first report of hirsuitism in women and hyperpigmentation in African Americans. [Table: see text]

scholarly journals The opioid growth factor-opioid growth factor receptor axis regulates cell proliferation of human hepatocellular cancer

2010 ◽  
Vol 298 (2) ◽  
pp. R459-R466 ◽  
Author(s):  
Diego M. Avella ◽  
Eric T. Kimchi ◽  
Renee N. Donahue ◽  
Hephzibah Rani S. Tagaram ◽  
Patricia J. McLaughlin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Hepatocellular Cancer ◽  
Cell Number ◽  
Treatment Modalities ◽  
Opioid Growth Factor ◽  
Inhibition Of Dna Synthesis ◽  
Relationship Of

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide, with a mortality rate approximating its incidence. Understanding the biology of these tumors, as well as treatment modalities, has been challenging. The opioid growth factor (OGF; [Met5]-enkephalin) and the OGF receptor (OGFr) form an endogenous growth-regulating pathway in homeostasis and neoplasia. In this investigation, we examined the relationship of the OGF-OGFr axis in HCC and define its presence, function, and mechanism. Using SK-HEP-1, Hep G2, and Hep 3B human HCC cell lines, we found that OGF and OGFr were present and functional. Exogenous OGF was observed to have a dose-dependent, reversible, and receptor-mediated inhibitory action on cell proliferation. Endogenous OGF was found to be constitutively produced and tonically active on cell replicative activities, with neutralization of this peptide accelerating cell proliferation. Silencing of OGFr using siRNA stimulated cell replication, even when exogenous OGF was added to the cultures, documenting its importance in mediating OGF activity. The mechanism of OGF-OGFr action on cell number was related to inhibition of DNA synthesis and not to apoptotic or necrotic pathways. Both OGF and OGFr were detected in surgical specimens of HCC, and no quantitative differences were recorded in peptide or receptor between pathological and normal specimens. These data are the first to report that the OGF-OGFr system is a native biological regulator of cell proliferation in HCC. The findings may provide important insight in designing treatment strategies for this deadly disease.

scholarly journals Treatment of Chronic Anal Fissure

2019 ◽  
Vol 19 (2) ◽  
pp. 67-71
Author(s):  
Abdullah Al Tarique ◽  
Md Manjur Alam
Keyword(s):  
Anal Fissure ◽  
Chronic Anal Fissure ◽  
Treatment Options ◽  
Dentate Line ◽  
Primary Treatment ◽  
Treatment Modalities ◽  
Healing Ulcer ◽  
Recurrence Rates ◽  
Support Device ◽  
Perineal Support

Chronic anal fissure is a non healing ulcer in the anoderm appearing as a painful tear below the dentate line. There are debates about the efficacy of different treatment options for chronic anal fissure. This review aims to evaluate existing and newer treatment modalities. Aspects of chronic anal fissure aetiology and pathogenesis are also reviewed. Glyceryl trinitrate (GTN) ointment, Diltiazem ointment can be used as first line and Botulinum toxin (BTX) injection as second line pharmacological treatment. The effects of these chemicals are not permanent with higher fissure recurrence rates. Lateral internal sphincterotomy is the operative treatment of choice for fissures with high anal tone. Flap anoplasty should be done for fissures with normal anal tone especially in female patients. Both surgical procedures can be used as primary treatment option. The newer treatment options like gonyautoxin, controlled balloon anal dilatation, closed anal spand fissurotomy need more research. Perineal support device can be used as an adjunct to other treatment modalities. Journal of Surgical Sciences (2015) Vol. 19 (2) : 67-71

scholarly journals Alcohol-Induced Neuropathy in Chronic Alcoholism: Causes, Pathophysiology, Diagnosis, and Treatment Options

2020 ◽  
Vol 8 (4) ◽  
pp. 87-97
Author(s):  
Iga Dudek ◽  
Danuta Hajduga ◽  
Cezary Sieńko ◽  
Amr Maani ◽  
Elżbieta Sitarz ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Peripheral Neuropathy ◽  
Alcohol Abuse ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Chronic Alcoholism ◽  
Treatment Modalities ◽  
Excessive Alcohol Consumption ◽  
Chronic Alcohol Abuse ◽  
Wide Range

Abstract Purpose of the Review Alcohol abuse causes a wide range of disorders that affect the nervous system. These include confusion, cerebellar ataxia, peripheral neuropathy, and cognitive impairment. Chronic and excessive alcohol consumption is the primary cause of peripheral neuropathy. It is worth noting that peripheral neuropathy has no reliable treatment due to the poor understanding of its pathology. Recent Findings Coasting is a major feature of alcoholic neuropathy, largely due to chronic alcohol abuse. Its major features are hyperalgesia, allodynia, and burning pain. Even though much research was done in this area, still we do not have a full understanding of the mechanism of alcoholic neuropathy. However, some theories have been proposed. These include direct or indirect effects of alcohol metabolites, impaired axonal transport, suppressed excitatory nerve pathway activity, or imbalance in neurotransmitters. Activation of spinal cord microglia, mGlu5 spinal cord receptors, and hypothalamic-pituitary-adrenal axis also seem to be implicated in the pathophysiology of this alcoholic neuropathy. The goal of treatment is to impede further damage to the peripheral nerves while also restoring their normal physiology. Alcohol abstinence, intake of balanced diets, and treatment with medications are suggested including benfotiamine, alpha-lipoic acid, acetyl-l-carnitine, vitamin E, methylcobalamin, myo-inositol, N-acetylcysteine, capsaicin, tricyclic antidepressants, or antiepileptic drugs. Summary This review focuses on the many pathways that play a role in the onset and development of alcohol-induced neuropathy, as well as present the possible treatment strategies of this disorder, providing insights into a further search of new treatment modalities.

Treatment Options for Depression: Women and Primary Service Providers

1999 ◽  
Vol 5 (2) ◽  
pp. 38 ◽  
Author(s):  
Bernadette Hood ◽  
Ronnie Egan ◽  
Heather Gridley ◽  
Christine Brew
Keyword(s):  
Pharmacological Treatment ◽  
Professional Training ◽  
Qualitative Methodology ◽  
Service Providers ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Psychosocial Interventions ◽  
Research Literature ◽  
Treatment Modalities ◽  
Primary Service

A substantive quantitative research literature base exists exploring aspects of treatment for depression. Major themes to emerge from this literature include the use of general practitioners (GPs) in preference to psychiatrists for treatment and the negative public attitudes toward the use of pharmacological treatment strategies for depression. The study reported in this paper utilises a qualitative methodology to explore the experiences and attitudes of women currently being treated for depression. Specifically the paper focusses on the women's attitudes toward psychological versus medical treatment options for the disorder. Attitudes toward treatment modalities of medical and non-medical primary service providers are also investigated. Several significant findings emerged from the study. Women interviewed expressed a sense of personal responsibility for both the occurrence and management of depression.Consequent to this belief psychosocial interventions were critical to 'getting well'. Medication was viewed positively by all women, not as a treatment for depression, rather as a means of relieving the extreme symptoms of the illness, therefore providing space for psychosocial interventions. Medical and non-medical service providers expressed an acceptance of the need for integrating psychological and pharmacological treatment strategies though all providers acknowledged their lack of skills in incorporating treatments outside of their professional training. The study provides insight into the belief structures which influence participants' behaviours, presenting a less polarised view of attitudes toward psychological and pharmacological interventions than suggested by the current quantitative literature.

Hemodynamics Associated With Intracerebral Arteriovenous Malformations: The Effects of Treatment Modalities

Neurosurgery ◽  
2017 ◽  
Vol 83 (4) ◽  
pp. 611-621 ◽  
Author(s):  
Vernard S Fennell ◽  
Nikolay L Martirosyan ◽  
Gursant S Atwal ◽  
M Yashar S Kalani ◽  
Francisco A Ponce ◽  
...  
Keyword(s):  
Arteriovenous Malformations ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Endovascular Embolization ◽  
Treatment Modalities ◽  
Cerebral Arteriovenous Malformations ◽  
Venous Outflow ◽  
Comprehensive Literature Review ◽  
Flow Through ◽  
Changes Over Time

Abstract The understanding of the physiology of cerebral arteriovenous malformations (AVMs) continues to expand. Knowledge of the hemodynamics of blood flow associated with AVMs is also progressing as imaging and treatment modalities advance. The authors present a comprehensive literature review that reveals the physical hemodynamics of AVMs, and the effect that various treatment modalities have on AVM hemodynamics and the surrounding cortex and vasculature. The authors discuss feeding arteries, flow through the nidus, venous outflow, and the relative effects of radiosurgical monotherapy, endovascular embolization alone, and combined microsurgical treatments. The hemodynamics associated with intracranial AVMs is complex and likely changes over time with changes in the physical morphology and angioarchitecture of the lesions. Hemodynamic change may be even more of a factor as it pertains to the vast array of single and multimodal treatment options available. An understanding of AVM hemodynamics associated with differing treatment modalities can affect treatment strategies and should be considered for optimal clinical outcomes.

Cancer Drug Delivery

2016 ◽  
pp. 52-95
Author(s):  
Jai N. Patel ◽  
Jeryl Villadolid
Keyword(s):  
Drug Delivery ◽  
Supportive Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Treatment Modalities ◽  
Cancer Drug ◽  
Cellular Mechanisms ◽  
Drug Dosing ◽  
New Treatment ◽  
Cancer Drug Delivery

Advancements in cancer drug delivery have led to the development of personalized oncology care through molecularly-driven targeted therapies. Understanding molecular and cellular mechanisms which drive tumor progression and resistance is critical in managing new treatment strategies which have shifted from empiric to biomarker-directed therapy selection. Biomarker-directed therapies have improved clinical outcomes in multiple malignancies as monotherapy and in combination with other treatment modalities, however the changing scope of treatment options presents new opportunities and challenges for research. Furthermore, pharmacogenetics may provide a rationale method of personalizing anticancer drug dosing and supportive care management for oncology patients. This chapter reviews biomarker classifications and pharmacogenetics in anticancer therapy and supportive care. Examples of biomarker-directed therapies and clinical assays, in addition to future directions of molecular profiling in oncology therapy management are discussed.

Sign in / Sign up

Export Citation Format

Share Document