Role of PI3K and EGFR in Oral Cancer Progression and Drug Resistance

Microvesicles are shed constitutively, or upon activation, from both normal and malignant cells. The process is dependent on an increase in cytosolic Ca2+, which activates different enzymes, resulting in depolymerization of the actin cytoskeleton and release of the vesicles. Drug resistance can be defined as the ability of cancer cells to survive exposure to a wide range of anti-cancer drugs, and anti-tumour chemotherapeutic treatments are often impaired by innate or acquired MDR (multidrug resistance). Microvesicles released upon chemotherapeutic agents prevent the drugs from reaching their targets and also mediate intercellular transport of MDR proteins.

Download Full-text

Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma

Cancers ◽

10.3390/cancers12020396 ◽

2020 ◽

Vol 12 (2) ◽

pp. 396

Author(s):

Estíbaliz Tamayo-Orbegozo ◽

Laura Amo ◽

Javier Díez-García ◽

Elena Amutio ◽

Marta Riñón ◽

...

Keyword(s):

Drug Resistance ◽

B Cell ◽

Hodgkin Lymphoma ◽

Cancer Progression ◽

Current Knowledge ◽

Cell Types ◽

Metabolic Reprogramming ◽

Non Hodgkin Lymphoma ◽

New Evidence

Mature B-cell non-Hodgkin lymphoma (B-NHL) constitutes a group of heterogeneous malignant lymphoproliferative diseases ranging from indolent to highly aggressive forms. Although the survival after chemo-immunotherapy treatment of mature B-NHL has increased over the last years, many patients relapse or remain refractory due to drug resistance, presenting an unfavorable prognosis. Hence, there is an urgent need to identify new prognostic markers and therapeutic targets. Podocalyxin (PODXL), a sialomucin overexpressed in a variety of tumor cell types and associated with their aggressiveness, has been implicated in multiple aspects of cancer progression, although its participation in hematological malignancies remains unexplored. New evidence points to a role for PODXL in mature B-NHL cell proliferation, survival, migration, drug resistance, and metabolic reprogramming, as well as enhanced levels of PODXL in mature B-NHL. Here, we review the current knowledge on the contribution of PODXL to tumorigenesis, highlighting and discussing its role in mature B-NHL progression.

Download Full-text

Role of VEGF-Flt-1 Signaling in Oral Cancer Progression

Oral Surgery Oral Medicine Oral Pathology and Oral Radiology ◽

10.1016/j.oooo.2014.07.149 ◽

2015 ◽

Vol 119 (3) ◽

pp. e136-e137

Author(s):

Ajiravudh Subarnbhesaj ◽

Mutsumi Miyauchi ◽

Chea Chanbora ◽

Nurina Febriyanti Ayuningtyas ◽

Phuong Thao Nguyen ◽

...

Keyword(s):

Oral Cancer ◽

Cancer Progression

Download Full-text

Cancer-Associated Fibroblasts in Oral Cancer: A Current Perspective on Function and Potential for Therapeutic Targeting

Frontiers in Oral Health ◽

10.3389/froh.2021.686337 ◽

2021 ◽

Vol 2 ◽

Author(s):

Kamila J. Bienkowska ◽

Christopher J. Hanley ◽

Gareth J. Thomas

Keyword(s):

Oral Cancer ◽

Cancer Progression ◽

Immune Cell ◽

Checkpoint Inhibitors ◽

Tumour Microenvironment ◽

Cancer Associated Fibroblasts ◽

Current Perspective ◽

And Function ◽

Exciting Development

The role of the tumour microenvironement (TME) in cancer progression and resistance to therapies is now widely recognized. The most prominent non-immune cell type in the microenvironment of oral cancer (OSCC) is cancer-associated fibroblasts (CAF). Although CAF are a poorly characterised and heterogenous cell population, those with an “activated” myofibroblastic phenotype have been shown to support OSCC progression, promoting growth, invasion and numerous other “hallmarks of malignancy.” CAF also confer broad resistance to different types of therapy, including chemo/radiotherapy and EGFR inhibitors; consistent with this, CAF-rich OSCC are associated with poor prognosis. In recent years, much CAF research has focused on their immunological role in the tumour microenvironment, showing that CAF shield tumours from immune attack through multiple mechanisms, and particularly on their role in promoting resistance to anti-PD-1/PD-L1 checkpoint inhibitors, an exciting development for the treatment of recurrent/metastatic oral cancer, but which fails in most patients. This review summarises our current understanding of CAF subtypes and function in OSCC and discusses the potential for targeting these cells therapeutically.

Download Full-text

The Role of Cysteine Cathepsins in Cancer Progression and Drug Resistance

International Journal of Molecular Sciences ◽

10.3390/ijms20143602 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3602 ◽

Cited By ~ 15

Author(s):

Magdalena Rudzińska ◽

Alessandro Parodi ◽

Surinder M. Soond ◽

Andrey Z. Vinarov ◽

Dmitry O. Korolev ◽

...

Keyword(s):

Drug Resistance ◽

Cancer Progression ◽

Cancer Biology ◽

Lysosomal Enzymes ◽

Tumor Biology ◽

Therapeutic Strategies ◽

Cysteine Cathepsins ◽

Aggressive Tumor ◽

Tumor Phenotypes

Cysteine cathepsins are lysosomal enzymes belonging to the papain family. Their expression is misregulated in a wide variety of tumors, and ample data prove their involvement in cancer progression, angiogenesis, metastasis, and in the occurrence of drug resistance. However, while their overexpression is usually associated with highly aggressive tumor phenotypes, their mechanistic role in cancer progression is still to be determined to develop new therapeutic strategies. In this review, we highlight the literature related to the role of the cysteine cathepsins in cancer biology, with particular emphasis on their input into tumor biology.

Download Full-text

Selected Micro RNAs Regulate Drug Resistance Genes in Breast Cancer.

10.21203/rs.3.rs-580368/v1 ◽

2021 ◽

Author(s):

Shumaila Zaib ◽

Azra Yasmin ◽

Nosheen Masood

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Cancer Progression ◽

Progression Free Survival ◽

Pten Gene ◽

Over Expression ◽

Micro Rnas ◽

Exact Etiology

Abstract Background: Breast cancer initiation is an unresolved phenomenon although many genes are known to be involved in its initiation but its exact etiology is still unexplained in many aspects and recently microRNAs are found to regulate many genes expressions. Method: This case control study has been designed to evaluate the role of selected miRNAs in gene expression and subsequent association with drug resistance. Genetic polymorphisms were confirmed by PCR-SSCP followed by sequencing and microRNA expression was measured by realtime PCR with specific primers. Follow up was done for patients whose samples were used in the study. Results: This study revealed 15 germline mutations in mdr1, 5 in ABCG2, 8 in BRCA1 and 8 in PTEN gene. These mutations were significantly associated with breast cancer compared with control tissues (P<0.05). miR-21, miR-146a and miR-328 were over expressed whereas miR-451 was under expressed. Progression free survival (PFS) was linked with reduced polymorphisms in genes as well as microRNAs. Conclusion: Over expression of miRNA-21 and miRNA-146a may lead towards lower expression of PTEN and BRCA1 genes causing cancer progression. miRNA-328 and miRNA-451 reduced expression resulted in overexpressed ABCG2 and MDR1 genes in this study.

Download Full-text

Mechanistic Insights Delineating the Role of Cholesterol in Epithelial Mesenchymal Transition and Drug Resistance in Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.728325 ◽

2021 ◽

Vol 9 ◽

Author(s):

Naaziyah Abdulla ◽

C. Theresa Vincent ◽

Mandeep Kaur

Keyword(s):

Drug Resistance ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Epithelial Mesenchymal Transition ◽

Cholesterol Metabolism ◽

Cholesterol Content ◽

Multi Drug Resistance ◽

Mesenchymal Transition ◽

Proposed Model

Despite the significant advancements made in targeted anti-cancer therapy, drug resistance constitutes a multifaceted phenomenon leading to therapy failure and ultimately mortality. Emerging experimental evidence highlight a role of cholesterol metabolism in facilitating drug resistance in cancer. This review aims to describe the role of cholesterol in facilitating multi-drug resistance in cancer. We focus on specific signaling pathways that contribute to drug resistance and the link between these pathways and cholesterol. Additionally, we briefly discuss the molecular mechanisms related to the epithelial-mesenchymal transition (EMT), and the documented link between EMT, metastasis and drug resistance. We illustrate this by specifically focusing on hypoxia and the role it plays in influencing cellular cholesterol content following EMT induction. Finally, we provide a proposed model delineating the crucial role of cholesterol in EMT and discuss whether targeting cholesterol could serve as a novel means of combatting drug resistance in cancer progression and metastasis.

Download Full-text

Current Molecular Concept of Oral Carcinogenesis and Invasion

Medicine Today ◽

10.3329/medtoday.v22i1.5605 ◽

1970 ◽

Vol 22 (1) ◽

pp. 38-42 ◽

Cited By ~ 2

Author(s):

Mahfujul Haq Khan ◽

Masuma Pervin Mishu ◽

Syed Touseef Imam

Keyword(s):

Oral Cancer ◽

Cancer Progression ◽

Cellular Proliferation ◽

Current Knowledge ◽

Oncogenic Viruses ◽

Chewing Tobacco ◽

Increased Risk ◽

Medicine Today ◽

Molecular Concept

Oral cancer is the commonest cancer in the South East Asia. Approximately 20-30% suffer from oral caner in out of all cancer patients diagnosed each year in this subcontinent. In Bangladesh the chronic use of betel quid and chewing tobacco in the mouth has been strongly associated with an increased risk for oral cancer. The last two-decade has been enormous advances in our understanding of cancer at molecular level. This review will give a out line of current knowledge of oral cancer, including basic over view of genetic mechanism involving cell regulation and cancer production. It is generally accepted that neoplasm arises from series of genetic alteration that lead to cellular proliferation & differentiation. In this review article, a brief discussion of important gene responsible for oral cancer, role of oncogenic viruses and molecular aspect of oral cancer progression, invasion & metastasis has been described. Key words: Oral Cancer; invasion; molecular concept. DOI: 10.3329/medtoday.v22i1.5605 Medicine Today Vol.22(1) 2010. 38-42

Download Full-text

Nuclear Lipid Microdomains Regulate Daunorubicin Resistance in Hepatoma Cells

International Journal of Molecular Sciences ◽

10.3390/ijms19113424 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3424 ◽

Cited By ~ 3

Author(s):

Michela Codini ◽

Carmela Conte ◽

Samuela Cataldi ◽

Cataldo Arcuri ◽

Andrea Lazzarini ◽

...

Keyword(s):

Drug Resistance ◽

Fatty Acid ◽

Cancer Progression ◽

Chain Fatty Acid ◽

Active Chromatin ◽

Long Chain Fatty Acid ◽

Lipid Microdomains ◽

Neutral Sphingomyelinase ◽

Long Chain

Daunorubicin is an anticancer drug, and cholesterol is involved in cancer progression, but their relationship has not been defined. In this study, we developed a novel experimental model that utilizes daunorubicin, cholesterol, and daunorubicin plus cholesterol in the same cells (H35) to search for the role of nuclear lipid microdomains, rich in cholesterol and sphingomyelin, in drug resistance. We find that the daunorubicin induces perturbation of nuclear lipid microdomains, localized in the inner nuclear membrane, where active chromatin is anchored. As changes of sphingomyelin species in nuclear lipid microdomains depend on neutral sphingomyelinase activity, we extended our studies to investigate whether the enzyme is modulated by daunorubicin. Indeed the drug stimulated the sphingomyelinase activity that induced reduction of saturated long chain fatty acid sphingomyelin species in nuclear lipid microdomains. Incubation of untreated-drug cells with high levels of cholesterol resulted in the inhibition of sphingomyelinase activity with increased saturated fatty acid sphingomyelin species. In daunodubicin-treated cells, incubation with cholesterol reversed the action of the drug by acting via neutral sphingomyelinase. In conclusion, we suggest that cholesterol and sphingomyelin-forming nuclear lipid microdomains are involved in the drug resistance.

Download Full-text

Hypoxia and Extracellular Acidification as Drivers of Melanoma Progression and Drug Resistance

Cells ◽

10.3390/cells10040862 ◽

2021 ◽

Vol 10 (4) ◽

pp. 862

Author(s):

Ewelina Dratkiewicz ◽

Aleksandra Simiczyjew ◽

Justyna Mazurkiewicz ◽

Marcin Ziętek ◽

Rafał Matkowski ◽

...

Keyword(s):

Drug Resistance ◽

Cancer Progression ◽

Immune Therapy ◽

Response To Therapy ◽

Braf V600e ◽

Relevant Research ◽

Extracellular Acidification ◽

Therapy Effectiveness ◽

Physicochemical Features

Hypoxia and elevated extracellular acidification are prevalent features of solid tumors and they are often shown to facilitate cancer progression and drug resistance. In this review, we have compiled recent and most relevant research pertaining to the role of hypoxia and acidification in melanoma growth, invasiveness, and response to therapy. Melanoma represents a highly aggressive and heterogeneous type of skin cancer. Currently employed treatments, including BRAF V600E inhibitors and immune therapy, often are not effective due to a rapidly developing drug resistance. A variety of intracellular mechanisms impeding the treatment were discovered. However, the tumor microenvironment encompassing stromal and immune cells, extracellular matrix, and physicochemical conditions such as oxygen level or acidity, may also influence the therapy effectiveness. Hypoxia and acidification are able to reprogram the metabolism of melanoma cells, enhance their survival and invasiveness, as well as promote the immunosuppressive environment. For this reason, these physicochemical features of the melanoma niche and signaling pathways related to them emerge as potential therapeutic targets.

Download Full-text