A new research perspective was published in Oncotarget's Volume 14 on May 10, 2023, entitled, “HER3- A key survival pathway and an emerging therapeutic target in metastatic colorectal cancer and pancreatic ductal adenocarcinoma.”

Colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) are highly metastatic cancers with poor survival rates. The tumor microenvironment has been shown to play a critical role in cancer progression and response to therapies. Endothelial cells (ECs) are a key component of the tumor microenvironment and promote cancer cell survival by secreting soluble factors that activate cancer-promoting signaling pathways. 

In this new perspective, researchers Omkar Desai and Rui Wang from Case Western Reserve University and University Hospitals Cleveland Medical Center discuss their studies and others that have identified HER3 as a key mediator of liver EC-induced chemoresistance and cancer cell growth in metastatic CRC and PDAC. 

“In complement to our studies, prior preclinical studies have shown that HER3-targeted therapies with antibodies and inhibitors have been effective in blocking tumor growth in several types of cancers [22, 23], specifically breast cancer [24], head and neck squamous cell carcinoma (HNSCC) [25], PDAC [25], and non-small cell lung cancer (NSCLC) [26]. However, translating the preclinical findings to clinical studies has shown limited impact on patient outcomes.”

In this article, the researchers discuss that HER3-targeted therapies may be effective in treating patients with HER3-expressing CRC and PDAC, and highlight the importance of applying HER3 expression as a predictive biomarker for patient response to HER3-targeted therapies. They also discuss the challenges encountered in past clinical trials of HER3-targeted therapies, including the role of NRG1 gene fusions, alternative HER3 activation mechanisms, and adaptive resistance mechanisms. Finally, the team concludes by suggesting the future directions of HER3-targeted therapies, including novel approaches to overcome chemoresistance and promote cancer cell death.

“In summary, we discovered that the surrounding liver EC microenvironment plays a key role in activating HER3 and promoting cell survival in mCRC and mPDAC, and potentially other types of cancer that metastasize to the liver.”

DOI - https://doi.org/10.18632/oncotarget.28421

Correspondence to - Rui Wang -  rxw517@case.edu

Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28421

Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/

Keywords - HER3, colorectal, pancreatic cancer, metastasis, microenvironment

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

SoundCloud - https://soundcloud.com/oncotarget
Facebook - https://www.facebook.com/Oncotarget/
Twitter - https://twitter.com/oncotarget
Instagram - https://www.instagram.com/oncotargetjrnl/
YouTube - https://www.youtube.com/@OncotargetJournal
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/

Media Contact
MEDIA@IMPACTJOURNALS.COM
18009220957

Oncotarget

HER3: Survival Pathway and Therapeutic Target in Metastatic Colorectal and Pancreatic Cancer

A conversation with science writer Philip Ball about his new illustrated history of alchemy

Elixirs, Experiments, and the Birth of Modern Science

Second opinions change the course of cancer care for many patients, and Ohio State experts are now using telehealth tech to increase access to these life-saving services.

Head-and-neck cancer surgeon Ricardo Carrau, MD, discusses the OSUCCC – James Online Second Opinon Program, which helps cancer patients make treatment decisions with clarity and confidence.

Follow The James Cancer-Free World Podcast:
· YouTube: https://go.osu.edu/C27H
· Spotify: https://go.osu.edu/C8pY
· Apple Podcasts: https://go.osu.edu/C2n6

Subscribe to The James on YouTube: https://www.youtube.com/@UCXGasnfbCpWYVW2RLTDPn4Q

Learn more about cancer care and research at The Ohio State University: 
Home: https://cancer.osu.edu
Blog: https://cancer.osu.edu/blog
News: https://cancer.osu.edu/news

Episode 196: Innovations in Cancer Second Opinions, with Dr. Riccardo Carrau

We are growing in our understanding of the long-term effects trauma and moral injury can have on bodies and spirits, including those within our own congregations. In this important and tender episode, Brandon and Whitney talk with former Army Chaplain and Episcopal priest David Peters about the ways faith communities can lean on Jesus’s life story to respond with love and care to these wounds. David’s latest book, Post-Traumatic Jesus: Reading the Gospel with the Wounded, offers a portrait of Jesus as living and speaking into a world that was familiar with trauma, from war to oppression to political violence, and reading the Gospels through that lens can create space for healing.

Host: Brandon Nappi with Whitney Coe

Guest: David Peters

Production: Goodchild Media

Instagram: @theleadersway.podcast berkeleydivinity.yale.edu/podcast

You can support our work at https://tinyurl.com/support-transforming-leaders



64: Post-Traumatic Jesus: A Conversation with David Peters

BUFFALO, NY — September 23, 2025 — A new #research paper was #published in Volume 17, Issue 8 of Aging-US on August 7, 2025, titled “Senescent cell heterogeneity and responses to senolytic treatment are related to cell cycle status during senescence induction.”

This study, led by first authors Francesco Neri and Shuyuan Zheng, together with corresponding authors Denis Wirtz, Pei-Hsun Wu, and Birgit Schilling from the Buck Institute for Research on Aging, the USC Leonard Davis School of Gerontology, and Johns Hopkins University, reveals that not all aging cells behave the same. The researchers identified key differences between senescent cell subtypes that may influence how well they respond to senolytic drugs. These findings could help guide the development of more effective therapies for age-related diseases.

Senescent cells are aged or damaged cells that stop dividing and accumulate in tissues over time. While they play a role in wound healing and protecting against cancer early in life, they can drive chronic inflammation and tissue decline with age. Researchers are exploring ways to selectively remove these cells using senolytic drugs. However, the large variety of senescent cell types has made it difficult to design treatments that work for all of them. This study aimed to better understand the functional differences among senescent cell subpopulations.

Using high-resolution imaging, the team analyzed thousands of human endothelial and fibroblast cells growing in the lab. They observed that cells that exited the cell cycle (stopped dividing) in a later phase showed stronger signs of senescence and were more sensitive to senolytic treatment. These cells also produced more IL-6, a molecule associated with inflammation. The findings suggest that DNA content, which varies depending on the cell cycle phase, plays an important role in how aging cells function and how they respond to drugs.

“We found that G2-arrested senescent cells feature higher senescence marker expression than G1-arrested senescent cells.”

This is the first clear evidence that senescent cells do not all respond equally to treatment. The results suggest that future senolytic therapies could be more successful if they are designed to target specific subtypes of senescent cells, especially those with greater inflammatory potential.

While this research was conducted in laboratory cell cultures, it provides a foundation for studying how these findings apply to living tissues. Future work will examine whether similar patterns occur in the body and how this knowledge could lead to more precise and effective treatments for age-related conditions. Understanding the diversity of aging cells is key to developing therapies that are both safer and more targeted.

DOI - https://doi.org/10.18632/aging.206299

Corresponding authors - Denis Wirtz — wirtz@jhu.edu, Pei-Hsun Wu — pwu@jhu.edu, and Birgit Schilling — bschilling@buckinstitute.org

Abstract video - https://www.youtube.com/watch?v=x8bhKEFLzqA

Sign up for free Altmetric alerts about this article - 
https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206299

Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts

Keywords - aging, cellular senescence, imaging, heterogeneity, senolytics, cell cycle

To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at:

Facebook - https://www.facebook.com/AgingUS/
X - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/@AgingJournal
LinkedIn - https://www.linkedin.com/company/aging/
Bluesky - https://bsky.app/profile/aging-us.bsky.social
Pinterest - https://www.pinterest.com/AgingUS/
Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc

MEDIA@IMPACTJOURNALS.COM

Aging-US

How Cell Cycle Status Affects Aging Cell Response to Senolytic Drugs

In this episode, Joseph Ho discusses his book, Developing Mission: Photography, Filmmaking, and American Missionaries in Modern China with Chloë Starr. The conversation ranges from camera technology in the interwar years to the documentation of disease in mission hospitals and circulation of missionary films documenting Japanese war crimes. If the creation of new types of images (such as baptism photographs) changes how we see the self and other, the cultural exchange of transnational images also played a role in Sino-US relations.

Joseph W. Ho, Developing Mission: Photography, Filmmaking, and American Missionaries in Modern China

BUFFALO, NY - September 24, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on September 22, 2025, titled “Loss of Trp53 results in a hypoactive T cell phenotype accompanied by reduced pro-inflammatory signaling in a syngeneic orthotopic mouse model of ovarian high-grade serous carcinoma.”

In this study, led by first author Jacob Haagsma and corresponding author Trevor G. Shepherd from the Verspeeten Family Cancer Centre and Western University, Canada, researchers investigated how the loss of Trp53 – a critical tumor suppressor gene – affects immune responses in ovarian cancer. The team found that deleting Trp53 led to more aggressive tumor growth and a weaker immune response. These findings help explain why some ovarian tumors may be resistant to immunotherapy and point to new ways to improve treatment.

High-grade serous ovarian carcinoma (HGSC) is a deadly cancer that is often diagnosed at a late stage. Immunotherapy, which enhances the body’s immune system to fight cancer, has shown limited effectiveness in treating this type of cancer. To better understand why, the researchers developed a mouse model that closely mimics human HGSC. They injected ovarian epithelial cells, with and without Trp53, into the fallopian tubes, the origin site of most ovarian cancers.

“In this study, we developed a syngeneic model reflecting both the site of origin and the genotype of early HGSC disease by deleting Trp53 in mouse oviductal epithelial (OVE) cells.”

Mice injected with cells lacking Trp53 developed faster-growing and more invasive tumors, reflecting how the disease typically progresses in humans. These tumors also had fewer active T cells, which are immune cells responsible for attacking cancer. Moreover, the T cells that were present appeared less capable of responding to the tumor, creating an immune environment that allowed cancer to grow uncontrolled.

Further analysis revealed that tumor cells without Trp53 had reduced activity in genes related to inflammation. These changes were associated with lower levels of key proteins that normally help immune cells detect and attack tumor cells. When the researchers collected tumor cells from the abdominal fluid of the mice—a condition that simulates advanced-stage disease—they observed even lower immune signaling than before. This suggests that as the tumor spreads, it becomes better at evading the immune system.

This study highlights how early genetic mutations can shape the interaction between tumors and the immune system. In particular, the loss of Trp53 appears to trigger a chain of events that weakens immune surveillance and accelerates tumor progression. These findings emphasize the need to consider both genetic mutations and the tumor environment when designing immunotherapies for ovarian cancer. Understanding how genes like Trp53 influence immune behavior may lead to more effective treatments and help identify which patients are most likely to benefit from immunotherapy.

DOI - https://doi.org/10.18632/oncotarget.28768

Correspondence to - Trevor G. Shepherd - tshephe6@uwo.ca

Abstract video - https://www.youtube.com/watch?v=WFQw0psuC3M

Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28768

Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

Facebook - https://www.facebook.com/Oncotarget/
X - https://twitter.com/oncotarget
Instagram - https://www.instagram.com/oncotargetjrnl/
YouTube - https://www.youtube.com/@OncotargetJournal
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/
Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh

MEDIA@IMPACTJOURNALS.COM

Loss of Trp53 Gene Promotes Tumor Growth and Immune Suppression in Ovarian Cancer

BUFFALO, NY — September 24, 2025 — A new #research paper was #published in Volume 17, Issue 8 of Aging-US on August 7, 2025, titled, “What is the clinical evidence to support off-label rapamycin therapy in healthy adults?”

In this study, led by Jacob M. Hands from The George Washington University School of Medicine and Health Sciences, researchers analyzed current research to determine whether low-dose rapamycin can extend healthspan or delay aging in healthy adults. While studies in animals have shown promising results, this review found no clear clinical evidence that the same benefits apply to humans. The findings point to the urgent need for larger, better-designed human trials before recommending rapamycin for off-label use to prevent aging.

Rapamycin, originally developed as a drug to suppress the immune system, has gained interest as a possible anti-aging therapy. It works by blocking a key cellular pathway called mTOR, which plays a role in growth and metabolism. In animal studies, blocking this pathway has extended lifespan. However, the translation of these results to humans remains uncertain. The current study examined clinical trials and observational studies involving healthy adults who took low doses of rapamycin or similar drugs.

“This paper has reviewed trials of low-dose mTOR inhibition therapy in human subjects.”

Some trials showed encouraging signs. For example, older adults treated with low-dose mTOR inhibitors showed stronger immune responses and fewer respiratory infections. Other studies suggested possible improvements in subjective well-being and physical performance, such as walking speed and strength. Still, none of the trials directly showed that rapamycin extends life or clearly slows the aging process. 

One small study using a biological aging model (PhenoAge) suggested that users might have reduced their biological age by nearly four years, but the estimate was based on average values, not individual patient data.

There are also concerns about side effects. While short-term use seems safe, some studies reported increases in blood lipids and markers of inflammation. Research on muscle health produced contradictory findings—some studies suggest rapamycin might reduce the body’s ability to build muscle. The impact on mental health is also unclear, with a few participants reporting increased anxiety during treatment.

The researchers emphasize that rapamycin’s role in human aging is still uncertain. Off-label use is growing among longevity clinics and individuals seeking anti-aging solutions, but there is no standard dose, and long-term safety is unknown. The authors advise that off-label use should be approached with caution, including careful monitoring and full disclosure about the limited evidence.

Overall, while animal studies have demonstrated promising effects, human trials have not yet shown that rapamycin can safely or effectively slow aging or extend lifespan. More rigorous and well-controlled studies are necessary before the drug can be considered a reliable option for healthy adults interested in longevity interventions.

DOI - https://doi.org/10.18632/aging.206300

Corresponding author - Jacob M. Hands - jacobhands@gwu.edu

Abstract video - https://www.youtube.com/watch?v=cdWUenvB_mY

Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts

To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at:

Facebook - https://www.facebook.com/AgingUS/
X - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/@AgingJournal
LinkedIn - https://www.linkedin.com/company/aging/
Bluesky - https://bsky.app/profile/aging-us.bsky.social
Pinterest - https://www.pinterest.com/AgingUS/
Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc

MEDIA@IMPACTJOURNALS.COM

Rapamycin Shows Limited Evidence for Longevity Benefits in Healthy Adults

Colorectal cancer is one of the most common—and deadliest—cancers worldwide. Once it spreads and reaches the metastatic stage, treatment becomes far more difficult. Tumors can also behave very differently from one patient to another, especially after multiple rounds of therapy. Precision oncology is helping to overcome these challenges by enabling clinicians to analyze each tumor’s unique genetic profile and tailor treatment accordingly.

This approach was recently highlighted in a case study published in Volume 16 of Oncotarget. The report detailed how a 62-year-old man with advanced colorectal cancer received a highly personalized treatment plan, developed by an international panel of experts, after completing all standard treatment options.

Full blog - https://www.oncotarget.org/2025/09/24/precision-oncology-in-metastatic-colorectal-cancer-a-real-world-case-study/

Paper DOI - https://doi.org/10.18632/oncotarget.28744

Correspondence to - Shai Magidi - shai.magidi@winconsortium.org

Abstract video - https://www.youtube.com/watch?v=uWDtWNgpK7A

Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28744

Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/

Keywords - cancer, precision oncology, molecular tumor board, colorectal carcinoma, cancer management

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

Facebook - https://www.facebook.com/Oncotarget/
X - https://twitter.com/oncotarget
Instagram - https://www.instagram.com/oncotargetjrnl/
YouTube - https://www.youtube.com/@OncotargetJournal
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/
Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh

MEDIA@IMPACTJOURNALS.COM

Precision Oncology in Metastatic Colorectal Cancer: A Real-World Case Study

In this episode of the Longevity & Aging Series, Girish Harinath from AgelessRx joins host Dr. Evgeniy Galimov to discuss a research paper he co-authored in Volume 17, Issue 4 of Aging-US, titled “Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results.”

DOI - https://doi.org/10.18632/aging.206235

Corresponding author - Stefanie L. Morgan - stefanie@agelessrx.com

Video interview - https://www.youtube.com/watch?v=7-NvskI8Ve0

Longevity & Aging Series - https://www.aging-us.com/longevity

Abstract

Design: This 48-week decentralized, double-blinded, randomized, placebo-controlled trial (NCT04488601) evaluated the long-term safety of intermittent low-dose rapamycin in a healthy, normative-aging human cohort. Participants received placebo, 5 mg or 10 mg compounded rapamycin weekly. The primary outcome measure was visceral adiposity (by DXA scan), secondary outcomes were blood biomarkers, and lean tissue and bone mineral content (by DXA scan). Established surveys were utilized to evaluate health and well-being. Safety was assessed through adverse events and blood biomarker monitoring.

Results: Adverse and serious adverse events were similar across all groups. Visceral adiposity did not change significantly (ηp2 = 0.001, p = 0.942), and changes in blood biomarkers remained within normal ranges. Lean tissue mass (ηp2 = 0.202, p = 0.013) and self-reported pain (ηp2 = 0.168, p = 0.015) improved significantly for women using 10 mg rapamycin. Self-reported emotional well-being (ηp2 = 0.108, p = 0.023) and general health (ηp2 = 0.166, p = 0.004) also improved for those using 5 mg rapamycin. No other significant effects were observed.

Conclusions: Low-dose, intermittent rapamycin administration over 48 weeks is relatively safe in healthy, normative-aging adults, and was associated with significant improvements in lean tissue mass and pain in women. Future work will evaluate benefits of a broader range of rapamycin doses on healthspan metrics for longevity, and will aim to more comprehensively establish efficacy.

Sign up for free Altmetric alerts about this article - 
https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206235

Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts

Keywords - aging, rapamycin, geroscience, longevity, healthspan

To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at:

Facebook - https://www.facebook.com/AgingUS/
X - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/@AgingJournal
LinkedIn - https://www.linkedin.com/company/aging/
Bluesky - https://bsky.app/profile/aging-us.bsky.social
Pinterest - https://www.pinterest.com/AgingUS/
Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc

MEDIA@IMPACTJOURNALS.COM

Longevity & Aging Series (S3, E6): Girish Harinath

Poet and priest Spencer Reece joins Leader’s Way host Brandon Nappi for a moving conversation about the power of poetry as an act of remembrance, as a response to violence, and as a culture maker and culture keeper. Listen to Father Reece offer spontaneous recitation and remind us of the ways poetry can bring us closer to the Divine.   

Host: Brandon Nappi

Guest: Spencer Reece

Production: Goodchild Media

Instagram: @theleadersway.podcast berkeleydivinity.yale.edu/podcast

You can support our work at https://tinyurl.com/support-transforming-leaders


65: Poetry Holds Us Together with Spencer Reece

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Oncotarget is now indexed by MEDLINE, PubMed and PMC/PubMed.

Read about the Oncotarget Scientific Integrity Process: https://www.oncotarget.com/scientific_integrity/

HER3: Survival Pathway and Therapeutic Target in Metastatic Colorectal and Pancreatic Cancer

Oncotarget Podcast

Related tracks