MicroRNA, AXL Gene Potentially Responsible for Drug Resistance in Certain Non-Small Cell Lung Cancers

Investigators have found that a small percentage of epidermal growth factor receptor (EGFR) inhibitor-resistant cancer cells are present in certain patients with non-small cell lung cancers (NSCLCs), potentially explaining tumor regrowth in these patients, according to a study published in eLife. Mutations in the EGFR growth receptor occur in approximately 15% of NSCLCs, according to the study.
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Considerations for Immunotherapy-Based Combinations in the Frontline Treatment of PD-L1–Positive NSCLC

Case-Based Roundtable Meetings Spotlight, Case-Based Roundtable Meetings Spotlight July 1 2021,. Ronald J. Scheff, MD, reviews the molecular testing practices for non–small cell lung cancer and frontline treatment of patients with PD-L1-positive non–small cell lung cancer during a Case-Based Roundtable event. Ronald J. Scheff, MD, reviews the molecular testing practices...

Barriers of Treating EGFR-Mutant NSCLC With Adjuvant Osimertinib

Nathan Pennell, MD, PhD, discusses the cost-effectiveness of adjuvant osimertinib in resected EGFR-mutant non-small cell lung cancer. Nathan Pennell, MD, PhD, a medical oncologist at the Cleveland Clinic, discusses the cost-effectiveness of adjuvant osimertinib (Tagrisso) in resected EGFR-mutant non-small cell lung cancer (NSCLC). According to Pennell, at a 5% improvement...

The Promising Future of Immunotherapies in Cancer Research

Dr. Mazzocchi discusses the limits and benefits of immunotherapies, as well as the importance of genetic testing in determining cancer diagnosis and treatment in patients. Mutations in cancer have always presented a challenge for doctors and patients alike. Lung cancer has several known mutations that have been extensively studied, with an ever-evolving list of inhibitors and therapies that followed suit.

ASCO 2021: New Data for NSCLC Treatment Options

Ben Levy, MD, The Johns Hopkins University School of Medicine, Melissa Johnson, MD, Tennessee Oncology, Edward Kim, MD, MBA, City of Hope National Medical Center, Jacob Sands, MD, Dana-Farber Cancer Institute, Alexander Spira, MD, PhD, FACP, Virginia Cancer Specialists, US Oncology. Jacob Sands, MD, reviews data regarding the investigational oral...
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Immunotherapies for Non-Small Cell Lung Cancer

Immunotherapy modifies some aspects of the body's immune system to help manage a number of illnesses, including non-small cell lung cancer (NSCLC). Certain cancers have distinct molecular features. By identifying them with genetic testing, doctors can select an immunotherapy drug that is designed to attack a patient's specific type of NSCLC in a more targeted way.

Smart combination therapy for liver cancer tackles drug resistance

Liver cancer is one of the most common cancer types worldwide and is especially common in China. A collaborative effort between researchers at the Netherlands Cancer Institute and Shanghai using CRISPR/Cas has led to the discovery that insensitivity to a liver cancer drug can be prevented if it is given in combination with a second drug.
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New York Real Estate Heats Up as Life Sciences Market Grows

New York City may be the business center for an awful lot of the world’s economy, but despite its size, population and access to venture capital as well as top academic institutions, it’s not typically viewed as a major site for life sciences startups. However, the last several years have marked several attempts to stimulate life sciences startups to pick the Big Apple.

PSMC2/CCND1 axis promotes development of ovarian cancer through regulating cell growth, apoptosis and migration

Ovarian cancer is known as one of the most common malignancies of the gynecological system, whose treatment is still not satisfactory because of the unclear understanding of molecular mechanism. PSMC2 is an essential component of 19 S regulatory granules in 26 S proteasome and its relationship with ovarian cancer is still not clear. In this study, we found that PSMC2 was upregulated in ovarian cancer tissues, associated with tumor grade and could probably predict poor prognosis. Knocking down the endogenous PSMC2 expression in ovarian cancer cells could decrease colony formation ability, cell motility and cell proliferation rate, along with increasing cell apoptosis rate. Cells models or xenografts formed by cells with relatively lower expression of PSMC2 exhibited weaker oncogenicity and slower growth rate in vivo. Moreover, gene microarray was used to analyze the alteration of gene expression profiling of ovarian cancer induced by PSMC2 knockdown and identify CCND1 as a potential downstream of PSMC2. Further study revealed the mutual regulation between PSMC2 and CCND1, and demonstrated that knockdown of CCND1 could enhance the regulatory effects induced by PSMC2 knockdown and overexpression of CCND1 reverses it. In summary, PSMC2 may promote the development of ovarian cancer through CCND1, which may predict poor prognosis of ovarian cancer patients.

Precise Management of EGFR exon 20-Positive Non–Small Cell Lung Cancer

Research shows that methods used to treat the wide epidermal growth factor receptor-positive population are often not successful for patients with specific biomarkers like EGFR exon 20 insertion mutations, highlighting an ongoing need for more targeted therapies. Non–small cell lung cancer (NSCLC) carries many disease variations that each require slightly...

Afatinib induces pro-survival autophagy and increases sensitivity to apoptosis in stem-like HNSCC cells

Afatinib, a second-generation tyrosine kinase inhibitor (TKI), exerts its antitumor effects in head and neck squamous cell carcinoma (HNSCC) by inducing intrinsic apoptosis through suppression of mTORC1. However, the detailed mechanism and biological significance of afatinib-induced autophagy in HNSCC remains unclear. In the present study, we demonstrated that afatinib induced mTORC1 suppression-mediated autophagy in HNSCC cells. Further mechanistic investigation revealed that afatinib stimulated REDD1-TSC1 signaling, giving rise to mTORC1 inactivation and subsequent autophagy. Moreover, ROS generation elicited by afatinib was responsible for the induction of the REDD1-TSC1-mTORC1 axis. In addition, pharmacological or genetic inhibition of autophagy sensitized HNSCC cells to afatinib-induced apoptosis, demonstrating that afatinib activated pro-survival autophagy in HNSCC cells. Importantly, in vitro and in vivo assays showed that afatinib caused enhanced apoptosis but weaker autophagy in stem-like HNSCC cells constructed by CDH1 knockdown. This suggested that blocking autophagy has the potential to serve as a promising strategy to target HNSCC stem cells. In conclusion, our findings suggested that the combination treatment with afatinib and autophagy inhibitors has the potential to eradicate HNSCC cells, especially cancer stem cells in clinical therapy.

BioSpace’s Business Report Highlights Sustained Growth and New Blood

The life sciences is always a frenetic sector when it comes to mergers & acquisitions, initial public offerings (IPOs) and Series A announcements (not to mention B and C rounds). But during the second quarter of 2021, these companies were especially busy bees – all positive signs that the industry is still booming coming out of the COVID-19 pandemic.

Frontline Treatment of Stage IV NSCLC: What’s Next?

Mark A. Socinski, MD, AdventHealth Cancer Institute, Martin Dietrich, MD, PhD, Florida Cancer Specialists, Roy S. Herbst, MD, PhD, Yale Cancer Center, Chaitali Nangia, MD, Patty and George Hoag Cancer Center, Sandip P. Patel, MD, University of California San Diego, Neal Edward Ready, MD, PhD, Duke Medical Center. Future projections...

Trending with Impact: LP-184 Retains Potency in Refractory Lung Cancer

Oncotarget published this trending research paper on April 13, 2021, entitled, "The acylfulvene alkylating agent, LP-184, retains nanomolar potency in non-small cell lung cancer carrying otherwise therapy-refractory mutations" by researchers from Lantern Pharma, Inc., Dallas, TX, and REPROCELL USA Inc., Beltsville, MD. Abstract: More than 40% of non-small cell lung cancer (NSCLC) patients lack actionable targets and require non-targeted chemotherapeutics. Many become refractory to drugs due to underlying resistance-associated mutations. KEAP1 mutant NSCLCs further activate NRF2 and upregulate its client PTGR1. LP-184, a novel alkylating agent belonging to the acylfulvene class is a prodrug dependent upon PTGR1. We hypothesized that NSCLC with KEAP1 mutations would continue to remain sensitive to LP-184. LP-184 demonstrated highly potent anticancer activity both in primary NSCLC cell lines and in those originating from brain metastases of primary lung cancers. LP-184 activity correlated with PTGR1 transcript levels but was independent of mutations in key oncogenes (KRAS and KEAP1) and tumor suppressors (TP53 and STK11). LP-184 was orders of magnitude more potent in vitro than cisplatin and pemetrexed. Correlative analyses of sensitivity with cell line gene expression patterns indicated that alterations in NRF2, MET, EGFR and BRAF consistently modulated LP-184 sensitivity. These correlations were then extended to TCGA analysis of 517 lung adenocarcinoma patients, out of which 35% showed elevated PTGR1, and 40% of those further displayed statistically significant co-occurrence of KEAP1 mutations. The gene correlates of LP-184 sensitivity allow additional personalization of therapeutic options for future treatment of NSCLC. Press release - https://www.oncotarget.com/news/pr/retaining-nanomolar-potency-in-lung-cancer-with-therapy-refractory-mutations/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27943 DOI - https://doi.org/10.18632/oncotarget.27943 Full text - https://www.oncotarget.com/article/27943/text/ Correspondence to - Aditya Kulkarni - aditya@lanternpharma.com Keywords - non-small cell lung cancer, acylfulvene, alkylating agent, PTGR1, LP-184 About Oncotarget Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957.