scholarly journals TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine and Immunotherapy

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 876
Author(s):  
Desh Deepak Singh ◽  
Dharmendra Kumar Yadav
Keyword(s):  
Growth Factor ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Therapeutic Options ◽  
High Rate ◽  
Treatment Modalities ◽  
P53 Signaling ◽  
Multiple Receptors ◽  
Potential Applications ◽  
Clinical Conditions

Triple-negative breast cancer (TNBC) is a heterogeneous, recurring cancer associated with a high rate of metastasis, poor prognosis, and lack of therapeutic targets. Although target-based therapeutic options are approved for other cancers, only limited therapeutic options are available for TNBC. Cell signaling and receptor-specific targets are reportedly effective in patients with TNBC under specific clinical conditions. However, most of these cancers are unresponsive, and there is a requirement for more effective treatment modalities. Further, there is a lack of effective biomarkers that can distinguish TNBC from other BC subtypes. ER, PR, and HER2 help identify TNBC and are widely used to identify patients who are most likely to respond to diverse therapeutic strategies. In this review, we discuss the possible treatment options for TNBC based on its inherent subtype receptors and pathways, such as p53 signaling, AKT signaling, cell cycle regulation, DNA damage, and programmed cell death, which play essential roles at multiple stages of TNBC development. We focus on poly-ADP ribose polymerase 1, androgen receptor, vascular endothelial growth factor receptor, and epidermal growth factor receptor as well as the application of nanomedicine and immunotherapy in TNBC and discuss their potential applications in drug development for TNBC.

scholarly journals Beyond Chemotherapy, PD-1, and HER-2: Novel Targets for Gastric and Esophageal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4322
Author(s):  
Ali Zubair Siddiqui ◽  
Khaldoun Almhanna
Keyword(s):  
Esophageal Cancer ◽  
Growth Factor ◽  
Patient Population ◽  
Treatment Options ◽  
Treatment Algorithm ◽  
Growth Factor Receptor ◽  
Incidence Rates ◽  
Treatment Modalities ◽  
Her 2 ◽  
Endothelial Growth Factor

Together, gastric cancer and esophageal cancer (EC) possess two of the highest incidence rates amongst all cancers. They exhibit poor prognoses in which the 5-year survival rate is dismal. In addition to cytotoxic chemotherapy, treatment efforts have been geared toward targeting human epidermal growth factor receptor 2 (HER-2), vascular endothelial growth factor (VEGF), and programmed death ligand-1 (PD-1). Although ample success has been recorded with these agents, gastric and esophageal cancer remain lethal, and further research into potential treatment alternatives is needed. In this article, we will review some of the targets at the forefront of investigation such as claudin, Dickkopf-related protein 1 (DKK-1), fibroblast growth factor receptor (FGFR), and matrix metalloproteinases (MMPs). These innovative target pathways are in the midst of clinical trials to be implemented in the treatment algorithm for this patient population. Ultimately, exploiting the oncogenic tendencies of these potential biomarkers creates an opportunity for precise treatment and improved prognosis for these cancers. Lastly, research aimed toward reversing PD-1 antibodies resistance by combining it with other novel agents or other treatment modalities is underway in order to expand existing treatment options for this patient population.

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 Protein Tyrosine Kinases: Their Roles and Their Targeting in Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 184
Author(s):  
Kalpana K. Bhanumathy ◽  
Amrutha Balagopal ◽  
Frederick S. Vizeacoumar ◽  
Franco J. Vizeacoumar ◽  
Andrew Freywald ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Protein Kinases ◽  
Tyrosine Kinases ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Tyrosine Protein Kinase ◽  
Mesenchymal Epithelial Transition Factor ◽  
The Impact

Protein kinases constitute a large group of enzymes catalysing protein phosphorylation and controlling multiple signalling events. The human protein kinase superfamily consists of 518 members and represents a complicated system with intricate internal and external interactions. Protein kinases are classified into two main families based on the ability to phosphorylate either tyrosine or serine and threonine residues. Among the 90 tyrosine kinase genes, 58 are receptor types classified into 20 groups and 32 are of the nonreceptor types distributed into 10 groups. Tyrosine kinases execute their biological functions by controlling a variety of cellular responses, such as cell division, metabolism, migration, cell–cell and cell matrix adhesion, cell survival and apoptosis. Over the last 30 years, a major focus of research has been directed towards cancer-associated tyrosine kinases owing to their critical contributions to the development and aggressiveness of human malignancies through the pathological effects on cell behaviour. Leukaemia represents a heterogeneous group of haematological malignancies, characterised by an uncontrolled proliferation of undifferentiated hematopoietic cells or leukaemia blasts, mostly derived from bone marrow. They are usually classified as chronic or acute, depending on the rates of their progression, as well as myeloid or lymphoblastic, according to the type of blood cells involved. Overall, these malignancies are relatively common amongst both children and adults. In malignant haematopoiesis, multiple tyrosine kinases of both receptor and nonreceptor types, including AXL receptor tyrosine kinase (AXL), Discoidin domain receptor 1 (DDR1), Vascular endothelial growth factor receptor (VEGFR), Fibroblast growth factor receptor (FGFR), Mesenchymal–epithelial transition factor (MET), proto-oncogene c-Src (SRC), Spleen tyrosine kinase (SYK) and pro-oncogenic Abelson tyrosine-protein kinase 1 (ABL1) mutants, are implicated in the pathogenesis and drug resistance of practically all types of leukaemia. The role of ABL1 kinase mutants and their therapeutic inhibitors have been extensively analysed in scientific literature, and therefore, in this review, we provide insights into the impact and mechanism of action of other tyrosine kinases involved in the development and progression of human leukaemia and discuss the currently available and emerging treatment options based on targeting these molecules.

Efficacy of Different Treatment Modalities for Eye Cancer in Bovines

2021 ◽  
Author(s):  
M. Prasanna Lakshmi ◽  
P. Veena ◽  
R.V. Suresh Kumar ◽  
D. Rani Prameela ◽  
K. Jagan Mohan Reddy
Keyword(s):  
Squamous Cell Carcinoma ◽  
Growth Factor ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Dietary Habits ◽  
Growth Factor Receptor ◽  
Surgical Excision ◽  
Treatment Modalities ◽  
Treatment Protocols ◽  
Hereditary Factors

Background: Bovine ocular squamous cell carcinoma also called cancer eye, represents the most economically important neoplasm in large animals. Hereditary factors, environmental factors (e.g: latitude, altitude, exposure to sunlight), lack of eyelid pigmentation, age and dietary habits have all been reported to play a role in the etiopathogenesis of bovine ocular squamous cell carcinoma. In addition, in cattle the etiology has been linked to a number of viral agents, especially bovine papilloma virus and bovine herpes virus type 1 and 5. Nevertheless, ultraviolet light, viruses and circumocular pigmentation are the major epidemiologic risk factors for the development of the tumor. The efficacy of different treatment modalities for eye cancer in bovines was studied.Methods: All the animals were divided in to four groups of six animals each. Surgical excision, intra lesion BCG vaccine, surgery with auto vaccine and surgery with mitomycin was the treatment protocols followed. Immunohistochemical studies were conducted to know the rate of proliferation of bovine ye cancer. Immunopositive reaction was observed against Vascular Endothelial Growth Factor and Epidermal Growth Factor Receptor in all the cases.Result: The benefits of different treatment modalities depended on nature, type, location and extensiveness of tumor. Early detection and aggressive treatment were essential in the successful management of these tumors. A multimodal treatment approach was recommended with surgery, immunotherapy and chemotherapy in providing 100% disease free interval.

scholarly journals Safety of Aflibercept in Metastatic Colorectal Cancer: A Literature Review and Expert Perspective on Clinical and Real-World Data

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 844 ◽  
Author(s):  
Kei Muro ◽  
Taylor Salinardi ◽  
Arvind Rup Singh ◽  
Teresa Macarulla
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Tolerability Profile ◽  
Real World Data ◽  
Asian Populations ◽  
Vegf Inhibitor

Background: Metastatic colorectal cancer (mCRC) represents a substantial health burden globally and an increasing challenge in Asian countries. Treatment options include chemotherapy plus a vascular endothelial growth factor (VEGF) inhibitor (such as bevacizumab, aflibercept or ramucirumab), or anti-epidermal growth factor receptor (EGFR) therapies. Aflibercept, a recombinant fusion protein, has been approved for treatment of mCRC in combination with FOLFIRI for patients whose disease progresses during or after treatment with an oxaliplatin-containing regimen, based on its efficacy and tolerability profile in clinical trials. This report aims to provide an overview of both clinical and real-world evidence and experience on the use of aflibercept in routine clinical practice, with a focus on European, American and Asian populations. Methods: A literature search was conducted in PubMed (on 28th February 2019) using the search terms ("aflibercept") and ("Colorectal"OR"CRC") to identify publications containing information on aflibercept-containing regimens. Results: The adverse events (AE) profile was similar between geographical locations. Across trials, real-world and retrospective studies, grade ≥ 3 hypertension and proteinuria were amongst the most frequently reported AEs. Conclusions: The safety profile of aflibercept is generally manageable and comparable across various geographic locations.

MC044h, a phase II trial of sorafenib in patients (pts) with metastatic neuroendocrine tumors (NET): A Phase II Consortium (P2C) study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4504-4504 ◽  
Author(s):  
T. J. Hobday ◽  
J. Rubin ◽  
K. Holen ◽  
J. Picus ◽  
R. Donehower ◽  
...  
Keyword(s):  
Growth Factor ◽  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Uncontrolled Hypertension ◽  
Eligibility Criteria ◽  
Grade 3

4504 Background: Treatment options for metastatic NET, including islet cell carcinoma (ICC) and carcinoid tumor (CT), are limited. These tumors frequently express vascular endothelial growth factor receptor-2 (VEGFR-2) and platelet derived growth factor receptor receptor-β (PDGFR-β). Sorafenib, a small-molecule inhibitor of the VEGFR-2 and PDGFR-β tyrosine kinase domains, is a rational targeted therapy to evaluate in NET. Methods: Eligibility criteria included: ECOG PS = 2, = 1 prior chemotherapy, good organ function and signed informed consent. Prior interferon and prior or concurrent octreotide at a stable dose were allowed. Pts unable to take oral medications, with uncontrolled hypertension or with symptomatic coronary artery disease were excluded. Pts received sorafenib 400 mg po BID. Primary endpoint was response by RECIST in two cohorts (ie, CT and ICC) using separate 2-stage phase II designs. Results: 93 pts were enrolled: (50 CT, 43 ICC). For pts evaluable for the primary endpoint, 4 of 41 (10%) CT pts and 4 of 41 (10%) ICC pts had a PR. There were 3 minor responses (MR = 20–29% decrease in sum of target lesion diameters) in CT pts and 9 MRs in ICC pts for PR+MR rate of 17% for CT pts and 32% for ICC pts. For pts evaluable, 6-month progression-free survival was observed in 8/20 CT and 14/23 ICC pts. Grade 3–4 toxicity occurred in 43% of pts, with skin (20%), GI (7%) and fatigue (9%) most common. Translational studies from tumor tissue will be presented. Conclusions: Sorafenib at 400 mg po BID has modest activity in metastatic neuroendocrine tumors, with frequent grade = 3 toxicity. Supported by NOI CM6225. No significant financial relationships to disclose.

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.

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