Oncotarget

A new research paper was published in Oncotarget on June 30, 2022, entitled, “Role of germline variants in the metastasis of breast carcinomas.”

Most cancer-related deaths in breast cancer patients are associated with metastasis, a multistep, intricate process that requires the cooperation of tumor cells, tumor microenvironment and metastasis target tissues. It is accepted that metastasis does not depend on the tumor characteristics but the host’s genetic makeup.

“However, there has been limited success in determining the germline genetic variants that influence metastasis development, mainly because of the limitations of traditional genome-wide association studies to detect the relevant genetic polymorphisms underlying complex phenotypes. “

Full press release: https://www.oncotarget.com/news/pr/oncotarget-role-of-germline-variants-in-the-metastasis-of-breast-carcinomas/

DOI: https://doi.org/10.18632/oncotarget.28250

Correspondence to: Aurelio A. Moya-García - Email: [email protected]

Special Collection on Breast Cancer: https://www.oncotarget.com/collections/breast-cancer/

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Keywords: breast cancer, germline variants, epistasis, network analysis, seed and soil

About Oncotarget:

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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Researchers from Eli Lilly and Company published a new research paper in Oncotarget on July 2, entitled, “Continuous treatment with abemaciclib leads to sustained and efficient inhibition of breast cancer cell proliferation.”

Worldwide, breast cancer (BC) is the second most common cancer. Pharmacologically targeting cyclin-dependent kinase 4 and 6 (CDK4 & 6) has proven to be a successful therapeutic approach in patients with estrogen receptor-positive (ER+) breast cancer.

Abemaciclib is the first FDA-approved CDK4 & 6 inhibitor (CDK4 & 6i) approved for the adjuvant treatment of HR+, HER2–, node-positive, early breast cancer (EBC) at high risk of recurrence and a Ki-67 score ≥20%. Differences have been observed in both efficacy and severity of neutropenia among the available CDK4 & 6i, generating interest in a possible mechanistic explanation. In this study, researchers examined the preclinical attributes of abemaciclib and other CDK4 & 6i using biochemical and cell-based assays.

“In vitro, abemaciclib preferentially inhibited CDK4 kinase activity versus CDK6, resulting in inhibition of cell proliferation in a panel of BC cell lines with higher average potency than palbociclib or ribociclib."

Abemaciclib showed activity regardless of HER2 amplification and phosphatidylinositol 3-kinase (PI3KCA) gene mutation status. In human bone marrow progenitor cells, abemaciclib showed lower impact on myeloid maturation than other CDK4 & 6i when tested at unbound concentrations similar to those observed in clinical trials. Continuous abemaciclib treatment provided profound inhibition of cell proliferation, and triggered senescence and apoptosis.

“After continuous dosing with abemaciclib, cells show sustained inhibition of cell proliferation that leads to irreversible effects through apoptosis. These preclinical results support the differentiated safety and efficacy profile of abemaciclib observed in clinical trials.”

DOI: https://doi.org/10.18632/oncotarget.28249

Correspondence to: María José Lallena - Email: [email protected]

Special Collection on Breast Cancer: https://www.oncotarget.com/collections/breast-cancer/

Breast Cancer Playlist:

https://www.youtube.com/watch?v=za5mOwlmcFM&list=PL1auE_IUnQH5ja5Ukr9S8FWFcbOqR6NHj

Keywords: abemaciclib, breast cancer, cell lines, CDK4/6, continuous dosing

About Oncotarget:

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Listen to a blog summary of a research paper published by Genes & Cancer, entitled, "KDM3A/Ets1/MCAM axis promotes growth and metastatic properties in Rhabdomyosarcoma.”

Rhabdomyosarcoma (RMS) and Ewing Sarcoma are among the most common types of cancer that develop in childhood. In recent years, new studies from researchers at the University of Colorado Denver Anschutz Medical Campus have contributed to the expansion of biomedical knowledge about how these diseases progress—paving a way for novel treatment strategies and therapeutics to inhibit the progression of these diseases.

INTRODUCTION

RMS consists of two predominant and distinct disease subtypes: fusion-positive RMS (FP-RMS) and fusion-negative RMS (FN-RMS). Fusion-positive RMS is the more aggressive subtype and shows a strong metastatic tendency to spread to other parts of the body. The sarcomagenesis of FP-RMS is driven by a genetic mutation that spawns the abnormal cancer-driving protein PAX3/FOXO1, or P3F. These P3F oncofusion genes use transcriptional and epigenetic mechanisms to drive FP-RMS pathogenesis. However, little was previously known about the mechanisms P3F uses for metastasis.

Recently, a team of dedicated researchers—Lays Martin Sobral, Marybeth Sechler, Janet K. Parrish, Tyler S. McCann, Kenneth L. Jones, Joshua C. Black, and Paul Jedlicka—endeavored to better understand the mechanisms and molecular pathways contributing to RMS progression, including the more aggressive FP-RMS subtype. In 2020, their influential research paper was published in Genes & Cancer and entitled, “KDM3A/Ets1/MCAM axis promotes growth and metastatic properties in Rhabdomyosarcoma.”

Full blog - https://www.impactjournals.com/journals/blog/genesandcancer/how-ewing-sarcoma-led-to-discoveries-in-rhabdomyosarcoma/

Keywords - pediatric cancer, rhabdomyosarcoma, KDM3A, Ets1, metastasis

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Genes & Cancer covers all aspects of the structure and function of oncogenes, growth suppressor and apoptotic genes.

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At the start of 2022, Oncotarget began publishing research papers in a continuous publishing format in yearly volumes. As of June 23, 2022, Oncotarget has published a total of 64 high-impact, oncology-focused papers within Volume 13.

Oncotarget’s Volume 13 consists of papers authored by numerous prestigious researchers and scientists from world-renowned institutions. Select papers in this Volume were chosen for inclusion in Oncotarget’s Special Collections on breast and lung cancer research.

Read the full press release - https://www.oncotarget.net/2022/06/23/oncotarget-new-oncology-focused-papers-published-in-volume-13/

Visit www.Oncotarget.com to read the latest publications in Volume 13.

About Oncotarget:

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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BUFFALO, NY- June 16, 2022 – Oncology-focused research papers published in Volume 12 of Genes & Cancer are now on PubMed.

Read short previews about some of the groundbreaking studies published in 2021 by Genes & Cancer. Visit YouTube to watch video previews of studies published by Genes & Cancer.

Full press release - https://www.impactjournals.com/journals/blog/genesandcancer/genes-cancer-now-on-pubmed-volume-12/

About Genes & Cancer:

Genes & Cancer covers all aspects of the structure and function of oncogenes, growth suppressor and apoptotic genes, their role in signal transduction and the mechanisms by which their expression and function are altered during tumor development. In addition to publishing manuscripts that directly relate to these areas of research, Genes & Cancer also aims to attract papers in the areas of genomics, drug development and systems biology.

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The Ride for Roswell is one of the nation’s largest cycling events—hosted by Roswell Park Comprehensive Cancer Center—to raise awareness and funds for cancer research and patient care. This charity bike ride, based out of Buffalo, New York, has brought people together for 26 years to celebrate cancer survivors, pay tribute to lives that have been lost, and to work together to support research and find a cure.

When it opened its doors in Buffalo in 1898, Roswell Park Comprehensive Cancer Center was the first cancer research-focused institution in the world. Today, this institution is one of only four National Cancer Institute-designated comprehensive cancer centers in the state of New York. Roswell Park Comprehensive Cancer Center is ranked by U.S. News & World Report as one of the best cancer hospitals in the United States.

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Visit the Open Access team page to join or donate today - https://give.roswellpark.org/site/TR/SpecialEvents/General?fr_id=1750&pg=team&team_id=8502

More about Impact Journals:

Impact Journals is an open-access publisher, focusing on topics surrounding cancer research, all fields of aging research, and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Our goal is life without disease.

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Dr. Alexander Pohlman from Rush Medical College, Rush University Medical Center, Chicago, IL, describes a recent review published by Oncotarget that he co-authored entitled, “The role of IGF-pathway biomarkers in determining risks, screening, and prognosis in lung cancer.”

DOI - https://doi.org/10.18632/oncotarget.28202

Correspondence to - Jeffrey A. Borgia - [email protected]

Abstract

Background: Detection rates of early-stage lung cancer are traditionally low, which contributes to inconsistent treatment responses and high rates of annual cancer deaths. Currently, low-dose computed tomography (LDCT) screening produces a high false discovery rate. This limitation has prompted research to identify biomarkers to more clearly define eligible patients for LDCT screening, differentiate indeterminate pulmonary nodules, and select individualized cancer therapy. Biomarkers within the Insulin-like Growth Factor (IGF) family have come to the forefront of this research.

Main Body: Multiple biomarkers within the IGF family have been investigated, most notably IGF-I and IGF binding protein 3. However, newer studies seek to expand this search to other molecules within the IGF axis. Certain studies have demonstrated these biomarkers are useful when used in combination with lung cancer screening, but other findings were not as conclusive, possibly owing to measurement bias and non-standardized assay techniques. Research also has suggested IGF biomarkers may be beneficial in the prognostication and subsequent treatment via systemic therapy. Despite these advances, additional knowledge of complex regulatory mechanisms inherent to this system are necessary to more fully harness the potential clinical utility for diagnostic and therapeutic purposes.

Conclusions: The IGF system likely plays a role in multiple phases of lung cancer; however, there is a surplus of conflicting data, especially prior to development of the disease and during early stages of detection. IGF biomarkers may be valuable in the screening, prognosis, and treatment of lung cancer, though their exact application requires further study.

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Keywords - IGF, lung cancer, biomarkers, screening, prognostication

About Oncotarget

Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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BUFFALO, NY- June 8, 2022 – A research paper was recently published in Oncotarget, entitled, “A novel group of genes that cause endocrine resistance in breast cancer identified by dynamic gene expression analysis.”

Breast cancer (BC) is the most common type of cancer diagnosed in women. Among female cancer deaths, BC is the second leading cause of death worldwide.

For estrogen receptor-positive (ER-positive) breast cancers, endocrine therapy is an effective therapeutic approach. However, in many cases, ER-positive tumors become unresponsive to endocrine therapy, and tumor regrowth can occur after treatment. While some genetic mutations contribute to resistance in some patients, the underlying causes of resistance to endocrine therapy are mostly undetermined.

“Endocrine therapies have been successful at improving cancer outcomes; however, the development of endocrine resistance, or resistance to inhibition of ER actions, remains a roadblock in breast cancer treatment.”

In the current study, researchers from UTHealth Houston, University of Chicago, University of Texas MD Anderson Cancer Center, and the University of Houston explored the dynamic behavior of the entire gene population to identify novel genes that play fundamental roles in the development and progression of endocrine-resistant breast cancer.

“In this study, we utilized a recently developed statistical approach to investigate the dynamic behavior of gene expression during the development of endocrine resistance and identified a novel group of genes whose time course expression significantly change during cell modelling of endocrine resistant BC development.”

To better understand the process of acquiring endocrine resistance and its underlying gene expression patterns, the researchers applied their recently developed statistical pipeline to datasets from a public functional genomics repository. They found dynamically regulated genes active in the process of endocrine resistance development and progression.

Their dynamic gene expression analysis identified 34 novel genes that significantly changed during cell modeling of endocrine-resistant breast cancer development. Expression of a subset of these genes was also differentially expressed in microarray analysis of endocrine-resistant and endocrine-sensitive tumor samples. Surprisingly, a subset of those genes was also differentially expressed in triple-negative breast cancer (TNBC) as compared with ER-positive BC.

“The findings suggest shared genetic mechanisms may underlie the development of endocrine resistant BC and TNBC.”

DOI: https://doi.org/10.18632/oncotarget.28225

Correspondence to: Michihisa Umetani – [email protected], and Vahed Maroufy – [email protected]

Special Collection on Breast Cancer: https://www.oncotarget.com/collections/breast-cancer/

Keywords: breast cancer, triple negative breast cancer, gene expression profiling, endocrine resistance, gene clustering

About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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Listen to a blog summary of a trending research paper published in Volume 13, entitled, “NF-κB over-activation portends improved outcomes in HPV-associated head and neck cancer.”

______________________________

Over the last 10 years in the United States, the human papillomavirus (HPV) has caused more head and neck squamous cell carcinomas (HNSCC) than uterine cervical cancers. Primarily caused either by exposure to HPV or to ethanol or tobacco, HNSCC is a disease that impairs fundamental tissues involved in respiration, speech and digestion. HPV-positive and -negative HNSCC have contrasting clinical, epidemiological and histological features.

“A major discovery in the recent past is that HPV associated HNSCC have improved survival compared to tobacco associated tumors.”

Therefore, treating HNSCC in accordance with HPV status is crucial for avoiding unnecessarily harsh therapeutic side effects in HPV+ HNSCC patients. However, while oncologic outcomes among patients with HPV+ HNSCC are generally favorable, approximately 30% experience a more aggressive disease course and recurrence. Coupled with increasing incidence worldwide, this highlights a growing need for the development of effective clinical stratification tools to accurately identify HPV+ HNSCC patients who have a good or poor prognosis.

In a new study, researchers—from Columbia University, University of Illinois Cancer Center, University of North Carolina at Chapel Hill, and Yale School of Medicine—developed a new tool aimed at better classifying HPV+ HNSCC patients with good or poor prognosis in an effort to personalize treatment and improve patient outcomes. Their trending research paper was published in Oncotarget on May 24, 2022, and entitled, “NF-κB over-activation portends improved outcomes in HPV-associated head and neck cancer.”

“To improve on genomic classification, we designed this study to provide a foundation for development of NF-κB related, RNA based classification strategies to better identify HPV+ HNSCC patients with good or poor prognosis that could potentially aid in future efforts towards treatment personalization.”

Full blog - https://www.oncotarget.org/2022/05/26/new-tool-uses-nf-%ce%bab-activity-to-classify-hpv-head-and-neck-cancer/

DOI - https://doi.org/10.18632/oncotarget.28232

Correspondence to - Wendell G. Yarbrough - [email protected], and Natalia Issaeva - [email protected]

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Press release - https://www.oncotarget.com/news/pr/oncotarget-nf-b-over-activation-portends-improved-outcomes-in-hpv-associated-head-and-neck-cancer/

Keywords - HPV, head and neck cancer, CYLD, TRAF3, NF-κB

About Oncotarget

Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

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BUFFALO, NY- May 25, 2022 – A new research paper was published in Oncotarget, entitled, “NF-κB over-activation portends improved outcomes in HPV-associated head and neck cancer.”

Head and neck squamous cell carcinoma (HNSCC) is a devastating disease that impairs fundamental tissues involved in respiration, phonation and digestion. HNSCC is primarily caused by exposure to either ethanol and tobacco or the human papillomavirus (HPV). Among patients with HPV+ HNSCC, there is a growing clinical demand to develop robust stratification tools to accurately identify patients with good or poor prognosis.

“While oncologic outcomes for HPV+ HNSCC are generally favorable, treatment paradigms developed for HPV-negative disease burden many survivors of HPV+ HNSCC with lifelong debilitating treatment-associated side effects [10]. On the other hand, ~30% of HPV+ HNSCC patients exhibit a more aggressive disease course and suffer recurrence [11, 12].”

Somatic mutations or deletions in TRAF3 or CYLD identified a subset of HPV+ HNSCC associated with improved outcome. A cross talk between canonical and non-canonical NF-κB signaling suggests that TRAF3 and CYLD affect both NF-κB pathways.

“Herein, we demonstrate that an RNA-based classifier trained on tumors harboring these mutations may improve prognostic classification (Figure 3A, 3B, Figure 4B and Supplementary Figure 1).”

To improve on genomic classification, researchers designed the current study to provide a foundation for development of NF-κB related, RNA based classification strategies to better identify HPV+ HNSCC patients with good or poor prognosis that could potentially aid in future efforts towards treatment personalization.

“This report validates and expands on our findings that significant expression changes related to NF-κB activity occur in the subset of HPV+ HNSCC tumors marked by TRAF3 or CYLD mutations. We are planning future studies investigating the importance of ‘long-tail’ mutations in the NF-κB pathway which might further illuminate the origins of NF-κB dysregulation in HPV+ HNSCC.”

“Given that methods to identify patients for deintensified therapy are imperfect, our improved classifiers may serve as prognostic biomarker to help clinicians with therapeutic decisions.”

DOI: https://doi.org/10.18632/oncotarget.28232

Correspondence to: Wendell G. Yarbrough and Natalia Issaeva

Email: [email protected] and [email protected]

Keywords: HPV, head and neck cancer, CYLD, TRAF3, NF-κB

About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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