Non–Small Cell Lung Cancer as a Precision Oncology Paradigm: Emerging Targets and Tumor Mutational Burden (TMB)

Non–small cell lung cancer (NSCLC), since the recognition of epidermal growth factor receptor (EGFR) mutations that sensitized tumors to EGFR tyrosine kinase inhibitors, has been a poster child for precision oncology in solid tumors. The emergence of resistance to the EGFR tyrosine kinase inhibitors led to the unveiling of multiple resistance mechanisms that are now recognized to be frequent mechanisms across multiple tumor types. Coevolution of technological advancements in testing methods available to clinical laboratories now has identified a growing number of molecularly defined subsets of NSCLC that have new therapeutic implications. In addition, identifying patients eligible for immunotherapy is another goal for precision oncology. Recently, studies suggest that TMB may be a promising biomarker for selecting patients with NSCLC for immunotherapy. This review focuses on emerging potentially targetable alterations specifically in RET, ERBB2 (HER2), MET, and KRAS and current evidence and controversies surrounding TMB testing.
Source: Advances in Anatomic Pathology - Category: Pathology Tags: Review Articles Source Type: research

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ins I Abstract Allogeneic cancer cell lines serve as universal source of tumor-associated antigens in cancer vaccines. Immunogenic high hydrostatic pressure-killed cancer cells derived from cell lines can be used for the generation of dendritic cell (DC)-based active cellular immunotherapy of non-small cell lung cancer (NSCLC). We investigated the expression of 12 known NSCLC tumor-associated antigens (TAA) (CEA, MAGE-A1, MAGE-A3, MAGE-A4, PRAME, hTERT, HER2, MUC1, Survivin, STEAP1, SOX2 and NY-ESO-1) in 6 NSCLC cell lines as candidates for the generation of DC-based lung cancer vaccine. We showed that the selecte...
Source: Immunology Letters - Category: Allergy & Immunology Authors: Tags: Immunol Lett Source Type: research
Authors: Han RH, Dunn GP, Chheda MG, Kim AH Abstract Metastases from melanoma, lung and breast cancer are among the most common causes of intracranial malignancy. Standard of care for brain metastases include a combination of surgical resection, stereotactic radiosurgery, and whole-brain radiation. However, evidence continues to accumulate regarding the efficacy of molecularly-targeted systemic treatments and immunotherapy. For non-small cell lung cancer (NSCLC), numerous clinical trials have demonstrated intracranial activity for inhibitors of EGFR and ALK. Patients with melanoma brain metastases may benefit from ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
AbstractPurpose of ReviewThe goal of our review is to describe the rationale for immunotherapy in the treatment of breast cancer brain metastases (BCBM), the current landscape of clinical trials for this disease process, and possible future directions based on anticipated results.Recent FindingsImmune checkpoint inhibition has shown efficacy in the treatment of several solid tumor brain metastases (i.e., melanoma and non-small cell lung cancer), but data specific to BCBM is relatively sparse. Preclinical studies in BCBM have illustrated a lower immune content in the brain microenvironment measured by tumor-infiltrating lym...
Source: Current Breast Cancer Reports - Category: Cancer & Oncology Source Type: research
Conclusions: ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with theKRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Conclusion MTDH is pro-oncogenic factor playing multifaceted and diverse roles in cancer progression. Its association and central role in regulating signaling pathways such a MAPK, wnt/β-catenin, PI3K/AkT, NF-κβ pathways in various cancers shows that it plays a vital role in metastasis. MTDH contribution to chemo and radiotherapy resistance provides a new direction for the development of anticancer therapeutics. Multiple mechanisms converge to promote expression of MTDH in cancers. Further studies are therefore warranted to determine whether the elevated MTDH expression has prognostic value for development...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, our WGCNA analysis identified candidate prognostic biomarkers for further basic and clinical researches. Introduction Breast cancer is a frequently diagnosed malignancy and the leading cause of cancer death among females around the world, accounting for 24% of cancer diagnoses and 15% of cancer deaths in females. According to Global Cancer Statistics 2018, there will be nearly 2.1 million new cases diagnosed globally, with ~62 thousand deaths. The incident rates of breast cancer increased in most developing countries during last decades, resulting from a combination of social and economic factors, incl...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study, we evaluated whether the combination of focused ultrasound (FUS) and microbubbles can improve adoptively NK-92MI cell infiltration into ovarian tumors through biodistribution, immunofluorescence, and flow cytometry. The treatment effects of using this strategy twice a week were explored. The potential molecular mechanism of FUS assisting NK cell therapy was also initially explored through evaluating the expression of ICAM1 and CX3CL1 by qRT-PCR. Our results indicated that FUS and microbubbles can improve NK-92MI cells’ infiltration into tumors, and the combination of FUS and NK-92MI cells had a better ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
This study was supported by the Shanghai Sailing Program [grant number 17YF1425200, 2017]; Chinese National Natural Science Funding [grant number 81702249, 2017]; Science and Technology Commission of Shanghai Municipality [grant number 17511103403, 2017]; The funder has no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments We acknowledge the ex...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSION: There is a great variation between countries with respect to all discussed topics. However, the majority recognized a necessity of introducing next generation sequencing (NGS)-based diagnostics and potential of testing from blood. The biggest problem in the treatment of NSCLC is still an access to innovative drugs. PMID: 30941946 [PubMed - in process]
Source: Journal of B.U.ON. - Category: Cancer & Oncology Tags: J BUON Source Type: research
ConclusionsOur results demonstrate that DOC induces CD8+ T cell recruitment to the tumor microenvironment by enhancing the secretion of HMGB1 and CXCL11, thus improving the anti-tumor efficacy, indicating that modulating the HMGB1-CXCL11 axis might be helpful for NSCLC treatment.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
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