scholarly journals NGAL as a Potential Target in Tumor Microenvironment

2021 ◽  
Vol 22 (22) ◽  
pp. 12333
Author(s):  
Elvira Crescenzi ◽  
Antonio Leonardi ◽  
Francesco Pacifico
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Stromal Cells ◽  
Checkpoint Inhibitors ◽  
Multiple Roles ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Promising Target ◽  
Car T ◽  
Inhibitory Signaling ◽  
Neutrophil Gelatinase

The signaling network between cancer and stromal cells plays a crucial role in tumor microenvironment. The fate of tumor progression mainly depends on the huge amount of information that these cell populations exchange from the onset of neoplastic transformation. Interfering with such signaling has been producing exciting results in cancer therapy: just think of anti-PD-1/anti-PD-L1/anti-CTLA-4 antibodies that, acting as immune checkpoint inhibitors, interrupt the inhibitory signaling exerted by cancer cells on immune cells or the CAR-T technology that fosters the reactivation of anti-tumoral immunity in a restricted group of leukemias and lymphomas. Nevertheless, many types of cancers, in particular solid tumors, are still refractory to these treatments, so the identification of novel molecular targets in tumor secretome would benefit from implementation of current anti-cancer therapeutical strategies. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a secreted protein abundantly expressed in the secretome of various human tumors. It represents a promising target for the multiple roles that are played inside cancer and stromal cells, and also overall in their cross-talk. The review focuses on the different roles of NGAL in tumor microenvironment and in cancer senescence-associated secretory phenotype (SASP), highlighting the most crucial functions that could be eventually targetable in cancer therapy.

scholarly journals Positron Emission Tomography for Response Evaluation in Microenvironment-Targeted Anti-Cancer Therapy

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 371
Author(s):  
Noboru Oriuchi ◽  
Shigeyasu Sugawara ◽  
Tohru Shiga
Keyword(s):  
Positron Emission Tomography ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Fdg Pet ◽  
Cell Tracking ◽  
Therapeutic Response ◽  
Tumor Response ◽  
Checkpoint Inhibitors ◽  
Emission Tomography ◽  
Positron Emission

Therapeutic response is evaluated using the diameter of tumors and quantitative parameters of 2-[18F] fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET). Tumor response to molecular-targeted drugs and immune checkpoint inhibitors is different from conventional chemotherapy in terms of temporal metabolic alteration and morphological change after the therapy. Cancer stem cells, immunologically competent cells, and metabolism of cancer are considered targets of novel therapy. Accumulation of FDG reflects the glucose metabolism of cancer cells as well as immune cells in the tumor microenvironment, which differs among patients according to the individual immune function; however, FDG-PET could evaluate the viability of the tumor as a whole. On the other hand, specific imaging and cell tracking of cancer cell or immunological cell subsets does not elucidate tumor response in a complexed interaction in the tumor microenvironment. Considering tumor heterogeneity and individual variation in therapeutic response, a radiomics approach with quantitative features of multimodal images and deep learning algorithm with reference to pathologic and genetic data has the potential to improve response assessment for emerging cancer therapy.

scholarly journals Targeting the Tumor Microenvironment for Improving Therapeutic Effectiveness in Cancer Immunotherapy: Focusing on Immune Checkpoint Inhibitors and Combination Therapies

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1188
Author(s):  
I-Tsu Chyuan ◽  
Ching-Liang Chu ◽  
Ping-Ning Hsu
Keyword(s):  
T Cell ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cell Activity ◽  
Immune Checkpoint Blockade ◽  
Immune Checkpoints

Immune checkpoints play critical roles in the regulation of T-cell effector function, and the effectiveness of their inhibitors in cancer therapy has been established. Immune checkpoint inhibitors (ICIs) constitute a paradigm shift in cancer therapy in general and cancer immunotherapy in particular. Immunotherapy has been indicated to reinvigorate antitumor T-cell activity and dynamically modulate anticancer immune responses. However, despite the promising results in the use of immunotherapy in some cancers, numerous patients do not respond to ICIs without the existence of a clear predictive biomarker. Overall, immunotherapy involves a certain degree of uncertainty and complexity. Research on the exploration of cellular and molecular factors within the tumor microenvironment (TME) aims to identify possible mechanisms of immunotherapy resistance, as well as to develop novel combination strategies involving the specific targeting of the TME for cancer immunotherapy. The combination of this approach with other types of treatment, including immune checkpoint blockade therapy involving multiple agents, most of the responses and effects in cancer therapy could be significantly enhanced, but the appropriate combinations have yet to be established. Moreover, the in-depth exploration of complexity within the TME allows for the exploration of pathways of immune dysfunction. It may also aid in the identification of new therapeutic targets. This paper reviews recent advances in the improvement of therapeutic efficacy on the immune context of the TME and highlights its contribution to cancer immunotherapy.

CDK1 in Breast Cancer: Implications for Theranostic Potential

2020 ◽  
Vol 20 (7) ◽  
pp. 758-767 ◽  
Author(s):  
Sepideh Izadi ◽  
Afshin Nikkhoo ◽  
Mohammad Hojjat-Farsangi ◽  
Afshin Namdar ◽  
Gholamreza Azizi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Cancer Therapeutics ◽  
Detection Methods ◽  
Breast Cancer Therapy ◽  
Promising Target ◽  
Anti Cancer

Breast cancer has been identified as one of the main cancer-related deaths among women during some last decades. Recent advances in the introduction of novel potent anti-cancer therapeutics in association with early detection methods led to a decrease in the mortality rate of breast cancer. However, the scenario of breast cancer is yet going on and further improvements in the current anti-cancer therapeutic approaches are needed. Several factors are present in the tumor microenvironment which help to cancer progression and suppression of anti-tumor responses. Targeting these cancer-promoting factors in the tumor microenvironment has been suggested as a potent immunotherapeutic approach for cancer therapy. Among the various tumorsupporting factors, Cyclin-Dependent Kinases (CDKs) are proposed as a novel promising target for cancer therapy. These factors in association with cyclins play a key role in cell cycle progression. Dysregulation of CDKs which leads to increased cell proliferation has been identified in various cancers, such as breast cancer. Accordingly, the development and use of CDK-inhibitors have been associated with encouraging results in the treatment of breast cancer. However, it is unknown that the inhibition of which CDK is the most effective strategy for breast cancer therapy. Since the selective blockage of CDK1 alone or in combination with other therapeutics has been associated with potent anti-cancer outcomes, it is suggested that CDK1 may be considered as the best CDK target for breast cancer therapy. In this review, we will discuss the role of CDK1 in breast cancer progression and treatment.

scholarly journals Combinatorial Approaches with Checkpoint Inhibitors to Enhance Anti-Tumor Immunity as Advantages of Targeting the Tumor Immune Microenvironment over Blocking Immune Checkpoint in Cancer Immunotherapy

2021 ◽  
pp. 501-547
Author(s):  
Elena Locci ◽  
Silvia Raymond
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Checkpoint Inhibitors ◽  
Repetitive Sequences ◽  
Treatment Strategies ◽  
Cellular Aging ◽  
The Body ◽  
Chromatin Interaction ◽  
Age Related

Aging is a condition in which the cell cycle is essentially irreversible and is caused by a variety of stressors such as obesity, radiation and chemotherapy. Aging cells that accumulate in the body during this period communicate with surrounding tissues through the production of proinflammatory proteins, called the SASP, and play a number of physiological and pathological roles. In the elderly, inflammatory agents of SASP increase various age-related diseases, including cancer; therefore, clarification of the SASP monitoring mechanism is essential for the development of new prevention and treatment strategies against age-related cancer. A group of Cancer Research Institute (CRI) of California South University researchers have hypothesized that the abnormal chromatin architecture observed in aging cells is related to SASP, and have begun analyzing chromatin interaction at the genome level and gene expression using next-generation sequencing techniques. They showed that the region containing the pericentromeric repetitive sequences called Human Satellite II (hSATII), which is genetically inactive in normal cells, has a significant state in aging cells; In addition, non-coding RNA expression (hSATII RNA) was significantly regulated during cellular aging. Further analysis showed that hSATII RNA regulated the expression of SASP-like inflammatory genes by disrupting chromatin interactions in some regions of the SASP gene through dysfunction of the CCCTC-binding factor (CTCF), which is important for maintaining genomic integrity. Small extracellular vehicles (EVs) secreted by cancer cells and stromal cells are dynamically involved in the development and progression of non-cellular tumors in the tumor microenvironment, and surprisingly more than the amount of hSATII RNA in small EVs caused by aging cells. Thus, our data suggest that hSATII RNA derived from aging stromal cells is transported to surrounding cells via small EVs and acts as an SASP-like inflammatory agent in the tumor microenvironment. In addition, the researchers found that hSATII RNA could be detected in cancer cells in surgical specimens of patients with primary colon cancer. Significantly, the population of hSATII-positive RNA cells was higher among cancer-associated fibroblasts than in fibroblasts in normal stromal tissues. These findings demonstrate the new role of hSATII RNA, which supports non-cellular tumor growth by secreting inflammatory agents similar to SASPs and small EVs. Understanding this molecular mechanism could facilitate new preventive and therapeutic development and provide solutions for future age-related injuries. Keywords: Cancer; Cells; Tissues; Tumors; Prevention; Prognosis; Diagnosis; Imaging; Screening; Treatment; Management

scholarly journals Oncolytic Adenoviruses for Cancer Therapy

2021 ◽  
Vol 22 (5) ◽  
pp. 2517
Author(s):  
Lorella Tripodi ◽  
Maria Vitale ◽  
Vincenzo Cerullo ◽  
Lucio Pastore
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Therapeutic Strategies ◽  
T Cell Response ◽  
Oncolytic Adenoviruses ◽  
Tumor Selectivity ◽  
Transgene Delivery ◽  
Fight Against Cancer

Many immuno-therapeutic strategies are currently being developed to fight cancer. In this scenario, oncolytic adenoviruses (Onc.Ads) have an interesting role for their peculiar tumor selectivity, safety, and transgene-delivery capability. The major strength of the Onc.Ads is the extraordinary immunogenicity that leads to a strong T-cell response, which, together with the possibility of the delivery of a therapeutic transgene, could be more effective than current strategies. In this review, we travel in the adenovirus (Ads) and Onc.Ads world, focusing on a variety of strategies that can enhance Onc.Ads antitumoral efficacy, passing through tumor microenvironment modulation. Onc.Ads-based therapeutic strategies constitute additional weapons in the fight against cancer and appear to potentiate conventional and immune checkpoint inhibitors (ICIs)-based therapies leading to a promising scenario.

Sign in / Sign up

Export Citation Format

Share Document