Addressing the elephant in the room, therapeutic resistance in non-small cell lung cancer, with epigenetic therapies

Carter, Corey A.; Zeman, Karen; Day, Regina M.; Richard, Patrick; Oronsky, Arnold L.; Oronsky, Neil; Lybeck, Michelle; Scicinski, Jan; Oronsky, Bryan

doi:10.18632/oncotarget.8205

Cited by 10 publications

(8 citation statements)

References 91 publications

(98 reference statements)

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“…Non-small cell lung cancer (NSCLC) is a prevalent malignant disease [1,2]. Effective prevention and treatment of NSCLC largely relies on a thorough understanding of the molecular mechanisms underlying the growth and invasion of NSCLCs, which requires the participation of cancer-related angiogenesis [3].…”

Section: Introductionmentioning

confidence: 99%

Placental Growth Factor Mediates Crosstalk Between Lung Cancer Cells and Tumor-Associated Macrophages in Controlling Cancer Vascularization and Growth

Zhu

Bai

et al. 2018

Cell Physiol Biochem

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Background/Aims: Assistance with tumor-associated vascularization is needed for the growth and invasion of non-small cell lung cancer (NSCLC). Recently, it was shown that placental growth factor (PLGF) expressed by NSCLC cells had a critical role in promoting the metastasis of NSCLC cells. However, the underlying molecular mechanisms remain elusive. Methods: Here, we first established a NSCLC model in mice that allows us not only to isolate tumor cells from non-tumor cells in the tumor, but also to trace tumor cells in living animals. Levels of PLGF, its unique receptor Flt-1, as well as transforming growth factor β1 (TGFβ1) was examined in tumor cells and tumor-associated macrophages (TAM) by RT-qPCR. A transwell well co-culture system and HUVEC assay were applied to study the crosstalk between NSCLC cells and TAM. Results: NSCLC cells produced and secreted PLGF to signal to tumor-associated macrophages (TAM) through surface expression of Flt-1 on macrophages. In a transwell co-culture system, PLGF secreted by NSCLC cells triggered macrophage polarization to a TAM subtype that promote growth of NSCLC cells. Moreover, polarized TAM seemed to secrete TGFβ1 to enhance the growth of endothelial cells in a HUVEC assay. Conclusion: The cross-talk between TAM and NSCLC cells via PLGF/Flt-1 and TGFβ receptor signaling may promote the growth and vascularization of NSCLC.

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Section: Introductionmentioning

confidence: 99%

Placental Growth Factor Mediates Crosstalk Between Lung Cancer Cells and Tumor-Associated Macrophages in Controlling Cancer Vascularization and Growth

Zhu

Bai

et al. 2018

Cell Physiol Biochem

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“…As described above, hypermethylation of cytosine in CpG islands (CGIs) by DNMTs of promoter regions has been shown to enable gene repression. Therefore, hypermethylation in tumor suppressor genes (TSGs) potentiates tumorigenic activity due to the disruption of critical cellular processes like cell cycle control, DNA repair and apoptosis [ 51 , 52 , 53 ].…”

Section: Gender Dna Methylation and Cancermentioning

confidence: 99%

The Relevance of Gender in Tumor-Influencing Epigenetic Traits

et al. 2019

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Tumorigenesis as well as the molecular orchestration of cancer progression are very complex mechanisms that comprise numerous elements of influence and regulation. Today, many of the major concepts are well described and a basic understanding of a tumor's fine-tuning is given. Throughout the last decade epigenetics has been featured in cancer research and it is now clear that the underlying mechanisms, especially DNA and histone modifications, are important regulators of carcinogenesis and tumor progression. Another key regulator, which is well known but has been neglected in scientific approaches as well as molecular diagnostics and, consequently, treatment conceptualization for a long time, is the subtle influence patient gender has on molecular processes. Naturally, this is greatly based on hormonal differences, but from an epigenetic point of view, the diverse susceptibility to stress and environmental influences is of prime interest. In this review we present the current view on which and how epigenetic modifications, emphasizing DNA methylation, regulate various tumor diseases. It is our aim to elucidate gender and epigenetics and their interconnectedness, which will contribute to understanding of the prospect molecular orchestration of cancer in individual tumors.

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“…90 The dismal 5-year survival rate of 17% 91 in stage 4 EOC is mainly attributable to the materialization of resistance, which has a genetic and epigenetic origin. 92 However, in contrast to the permanence of genetic defects, epigenetic mechanisms are forceful and potentially reversible with epigenetic therapies, which accounts for their appeal when used as pretreatment "primers" to prevent or reverse nonresponsiveness to chemotherapy. Previous experience with RRx-001, an investigational tumor-related macrophage and neutrophil depolarizing agent with epigenetic and vascular normalization properties, has demonstrated resensitization to platinum in other tumor types, like colorectal, small cell lung cancer (SCLC), and non-SCLC (NSCLC).…”

Section: Treatment Of Platinum Refractory Ocmentioning

confidence: 99%

Efficacy of PARP Inhibitors in the Treatment of Ovarian Cancer: A Literature-Based Review

Goswami

Koyyala

Goyal

et al. 2019

Asian Journal of Oncology

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Poly (ADP-ribose) polymerase (PARP) inhibitors are a unique class of therapeutic agents that focus on tumors with deficiencies in the homologous recombination DNA repair mechanism. Genomic instability outlines high-grade serous ovarian cancer, with 50% of all tumors displaying defects in the important DNA repair mechanism of homologous recombination. Earlier research studies have demonstrated considerable efficiency for PARP inhibitors in patients with germ line breast-related cancer antigens 1 and 2 (BRCA-1/BRCA-2) mutations. It has also been observed that BRCA wild-type patients with other defects in the homologous recombination repair mechanism get benefited from this therapy. Companion homologous recombination deficiency (HRD) scores are being developed to guide the selection of patients that are most likely to benefit from PARP inhibition. The selection of PARP inhibitor is mainly dependent upon the number of prior therapies and the presence of a BRCA mutation or HRD. The identification of cases which are most likely to get benefited from PARP inhibitor therapy in view of HRD and other biomarker assessments is still challenging. The purpose of this review is to focus and describe the current evidences for PARP inhibitors in ovarian malignancy, their mechanism of action, and the outstanding issues, including the rate of long-term toxicities and the evolving resistance.

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Addressing the elephant in the room, therapeutic resistance in non-small cell lung cancer, with epigenetic therapies

Cited by 10 publications

References 91 publications

Placental Growth Factor Mediates Crosstalk Between Lung Cancer Cells and Tumor-Associated Macrophages in Controlling Cancer Vascularization and Growth

Placental Growth Factor Mediates Crosstalk Between Lung Cancer Cells and Tumor-Associated Macrophages in Controlling Cancer Vascularization and Growth

The Relevance of Gender in Tumor-Influencing Epigenetic Traits

Efficacy of PARP Inhibitors in the Treatment of Ovarian Cancer: A Literature-Based Review

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