Blog | Page 9 of 12 | Mikhail Blagosklonny Oncotarget

Mikhail Blagosklonny Oncotarget

New Study: Vaccine Enhances Breast Cancer Treatment

October 27, 2021

Researchers conducted a study to examine the efficacy of adding the P10s-PADRE vaccine to chemotherapy treatments for patients with HR+/HER2− breast cancer.

Listen to an audio version of this article

The most common type of breast cancer in the United States is HR+/HER2− breast cancer. Patients with HR+/HER2− breast cancer often face the threat of distant recurrence—long after the completion of their treatment. Previous studies have found that high levels of tumor infiltrating lymphocytes (TILs) were associated with improved outcomes and recurrence-free survival in patients with HR+/HER2− breast cancer. These studies and many others have prompted researchers to further develop and test cancer vaccinesin an effort to elicit anti-tumor immune responses in these patients.

“Therefore, a rational combination therapy that enhances the immune-stimulatory properties of NAC [neoadjuvant chemotherapy], can provide long-term survival benefits for this patient population.”

Researchers from University of Arkansas for Medical Sciences, University of Texas Southwestern, Highlands Oncology Group, and Université Claude Bernard Lyon 1 conducted a new single-arm Phase Ib clinical trial. Early-stage HR+/HER2− breast cancer patients were treated with carbohydrate-mimetic peptides, the P10s-PADRE vaccine, in combination with chemotherapy treatments. Their paper was chosen as the cover of Oncotarget’s Volume 12, Issue 22, and entitled, “P10s-PADRE vaccine combined with neoadjuvant chemotherapy in ER-positive breast cancer patients induces humoral and cellular immune responses.”

“The main objective of our study was to determine an appropriate schedule to be used for adding the P10s-PADRE vaccine to cancer chemotherapy in the neoadjuvant setting considering the ability of the vaccine to elicit adequate antibody response.”

The Study

After meeting the study’s detailed inclusion/exclusion criteria, a total of 25 patients with HR+/HER2− breast cancer were selected to partake in this single-arm Phase Ib clinical trial. Patients were divided into five cohorts (five patients per cohort): A, B, C, D, and E. Each patient was treated with a combination of four therapies over the course of 22-25 weeks, including three doses of thepeptide-based P10s-PADRE cancer vaccine, four doses of Cyclophosphamide (chemotherapy), four doses of Doxorubicin (chemotherapy) and four doses of Docetaxel (chemotherapy). Using a cohort-specific treatment schedule for the previously stated combination of therapies, the researchers assessed the feasibility, safety and immunogenicity achieved in each cohort and each patient.

Additionally, patients underwent surgery between weeks 26 and 33 (four to eight weeks after their last chemotherapy treatment). Each cohort also had a cohort-specific blood draw schedule—blood was drawn at eight different times in the 73-week time frame. Blood draws were used to conduct flow cytometry, measure the concentration of cytokines, natural killer (NK) cells and antibodies, and to determine the presence of anti-peptide antibody response and the percentage of TILs. The researchers observed that all five cohorts saw a significant reduction in tumor size.

“The data suggest that subjects enrolled in schedule C generated a more consistent and robust antibody response, therefore schedule C appears as the schedule of choice for future combination therapy.”

Their findings concluded that, in combination with chemotherapy, P10s-PADRE immunization in HR+/HER2− breast cancer patients induced “acceptable” antibody responses in study cohorts C and E. The treatment schedule in cohort C demonstrated the strongest antibody response by affecting the expression levels of NK-cell markers, stimulating the production of cytokines, T-cells and TILs. However, the researchers note that continued analysis of the blood samples collected could show serum antibodies may begin to appear later on in patients enrolled in the other treatment schedules.

Conclusion

“This Phase Ib clinical trial of the P10s-PADRE vaccine shows that immunization in combination with a standard-of-care NAC is feasible and well-tolerated. Combination therapy induces antibody response, stimulates activation of NK cells, and is associated with infiltration of T cells in tumor microenvironment. Randomized phase II trials focusing on treatment schedule C are needed to validate current findings and evaluate clinical efficacy.”

Click here to read the full research paper, published by Oncotarget.

YOU MAY ALSO LIKE: More Oncotarget Videos on LabTube

—

Oncotarget is a unique platform designed to house scientific studies in a journal format that is available for anyone to read—without a paywall making access more difficult. This means information that has the potential to benefit our societies from the inside out can be shared with friends, neighbors, colleagues, and other researchers, far and wide.

For media inquiries, please contact media@impactjournals.com.

Oncotarget

EMT Resistance in Cancer Cells and Two Potential Causes

October 21, 2021

Researchers used mathematical modeling to investigate mechanisms that drive the elusive phenomenon of cancer cell resistance to epithelial-mesenchymal transition (EMT).

Epithelial–mesenchymal transition (EMT): losing cell polarity and cell adhesion to gain migratory and invasive properties.

Listen to an audio version of this article

Cancer cells have been known to use sagacious methods of evading apoptosis and mysteriously overcoming powerful anti-cancer therapies. One such method of evasion has recently been identified as the process of epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition (MET). These transitions enable epithelial cells (structural/fixed) to gain mesenchymal cell (differentiating/mobile) functions, and vice versa. Researchers believe that epithelial-mesenchymal plasticity (EMP) allows cancers to become therapy resistant, determines cancer aggressiveness and allows metastatic cancer to mobilize and spread.

“Such dynamic and reversible switching can help tumor cells to overcome various challenges during disease progression such as anoikis [6], and assaults by the immune system [7].”

These processes and their characterization in cancer have been studied, however, questions remain about their molecular determinants and degree of reversibility, or irreversibility, in different cell populations and environments. To further elucidate EMT, researchers from Rice University, Northeastern University and the Indian Institute of Science used mechanistic mathematical models to identify possible mechanisms that may drive EMT response to an EMT-inducing signal in a given isogenic cell population. Their paper was published by Oncotarget in 2020, and entitled, “Epigenetic feedback and stochastic partitioning during cell division can drive resistance to EMT.”

EMT/MET Reversibility/Irreversibility

In the introduction of this paper, the authors discuss results from previous research about the reversibility and irreversibility of EMT/MET. EMT can be triggered by various EMT-inducing external signals, such as TGFβ or by adjusting the levels of EMT-specific transcription factors (EMT-TFs). They report that, in cells stimulated over shorter durations (between two and six days), cells may revert back to an epithelial state after withdrawal of the signal/stimulus. They also explain that cells that have been stimulated over longer durations (10+ days) may render EMT irreversible and to become “locked” in a mesenchymal state.

Researchers suspect the existence of a “tipping point” after continued signal/stimulus exposure is what results in irreversible EMT. Multiple mechanisms have been proposed as responsible for this tipping point, including epigenetic alterations and self-stabilizing feedback loops in regulatory circuits. However, there remains a need for studies to investigate the mechanistic basis that causes epithelial cells to be resistant to undergoing EMT, or the irreversibility of MET.

“Some sporadic observations about the resistance of epithelial cells to undergo EMT have been reported [14, 24], but a causative mechanistic understanding still remains elusive.”

The Study

To investigate the mechanisms that enable the irreversibility of MET, or lack of EMP, the researchers in this study used mechanism-based mathematical modeling. Their experimental observations indicated that a global epigenetic program limiting the action of ZEB1 was found to underlie epithelial trait retention in cells exposed to persistent Twist1 activation for 21 days. They demonstrated a possible underlying mechanism by which GRHL2 overexpression can resist EMT. Importantly, the researchers found that, from a single isogenic cell population, two subpopulations of cells emerged and responded differently to the EMT-signalling.

“Here, we propose two independent mechanism[s] that may explain the resistance of epithelial tumor cells to undergo EMT: 1) epigenetic feedback mediated via GRHL2—an MET-inducing transcription factor (MET-TF) [25–27]; and 2) stochastic partitioning of parent cell biomolecules among the daughter cells at the time of cell division [28–30].”

Aside from epigenetic mediation involving GRHL2, the researchers believe varying EMT-signal responses within isogenic cell populations are caused by stochastic partitioning of molecules during cell division. The researcher described this phenomenon as a type of incongruent “noise” that takes place when cells divide.

“Such noise in the distribution of molecules may affect cell-fate and drive non-genetic heterogeneity [28–30], leading to different phenotypic distributions in terms of EMT [3].”

Conclusion

The team concluded that MET should not only be considered the reverse process of EMT, as important and distinct processes may be involved in both EMT and MET transformations. The authors are forthcoming about limitations in their study—indicating that a more detailed molecular mechanism-based epigenetic model would provide better insights into EMT. They also note that they did not consider spatial effects in their model, where more dense or spread out cell populations and access to signal strength, nutrients and oxygen may change outcomes.

“Future efforts should decode the molecular mechanisms of any such epigenetic feedback of GRHL2 on ZEB1 expression as well as track the distribution of molecules during cell divisions happening while cells are being induced to undergo EMT/MET.”

Click here to read the full research paper published by Oncotarget.

Watch, read or listen to an Oncotarget Interview with Drs. Herbert Levine and Mohit Kumar Jolly as they discuss this paper.

YOU MAY ALSO LIKE: More Oncotarget Videos on LabTube

—

For media inquiries, please contact media@impactjournals.com

Oncotarget

Trending With Impact: Unconventional Method Effectively Targets NSCLC

October 4, 2021

Researchers developed a divergent strategy to treat non-small cell lung cancer (NSCLC).

The Trending with Impact series highlights Oncotarget publications attracting higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Oncotarget.com.

—

Listen to an audio version of this article

The mammalian target of rapamycin (mTOR) operates within two distinct protein complexes—mTOR complex 1 (mTORC1) and complex 2 (mTORC2). These protein complexes are not yet fully understood, as they were only recently identified in humans in 1994. What researchers do know is that mTORC1 is involved in the regulation of many cellular processes and is a key mediator of cell growth and proliferation. mTORC1 is activated by growth factor receptor signals through the PI3K–AKT and RAS–ERK mitogen-activated protein kinase (MAPK) pathways.

The PI3K/AKT/mTOR pathway may be an efficacious target in the treatment of patients with non-small cell lung cancer (NSCLC). This theory is based on the identification of particular gene mutations in NSCLC that are associated with the PI3K/AKT/mTOR pathway. However, previous studies have not yet succeeded in defining an effective monotherapy or combination of therapies that targets this pathway while improving NSCLC patient outcome.

Researchers from Institut Curie, PSL University, Xentech, BioPôle Alfort, Hôpital Foch, and Centre Léon Bérard designed a study using a new methodology to test treatment combinations based on specific targets identified as biomarkers of resistance to PI3K-targeting treatments, and not based on the NSCLC mutations themselves. Their trending research paper was published by Oncotarget in 2021 and entitled, “High in vitro and in vivo synergistic activity between mTORC1 and PLK1 inhibition in adenocarcinoma NSCLC.”

“Our main strategy was therefore, using a panel of NSCLC PDXs, (i) to define predictive markers of response to RAD001 therapy and (ii) to identify possible combinations of treatments that may be able to reverse RAD001 resistance.”

THE STUDY

Researchers tested RAD001/Everolimus (an mTORC1 inhibitor) in vivo using NSCLC Patient-Derived Xenografts (PDXs), which demonstrated high antitumor efficacy. They next aimed to define predictive markers of response to RAD001 using real-time quantitative RT-PCR assays.

“In order to define predictive markers of response to RAD001, we used real-time quantitative RT-PCR assays to quantify the mRNA expression of a large number of selected genes.”

The team found three significantly highly expressed and targetable genes in NSCLC tumors resistant to RAD001: PLK1, CXCR4 and AXL. They then analyzed these genes for their prognostic value among NSCLC patients that were found in the publicly available database KMPLOT. This analysis revealed that of the three genes evaluated, only one high-gene expression was correlated with a negative impact on overall survival of patients with adenocarcinoma: PLK1. Given this data, the researchers next evaluated the in vivo efficacy of RAD001 combined with a PLK1 inhibitor, volasertib, in four PDX models. The RAD001 + volasertib combination demonstrated dramatic efficacy in three of the four models.

“In all tested PDXs, except LCF29, we have observed a significant, but variable, improvement of the antitumor efficacy of RAD001 + volasertib in comparison to each monotherapy (Figure 2A).”

To define this RAD001 + volasertib drug combination’s mechanism of action, the researchers conducted a pharmacodynamics (PD) study. The team then evaluated post-therapeutic proteins involved in the cell cycle, vascularization and carbonic anhydrase IX expression. These results were then validated using in vitro studies.

CONCLUSION

“Our determination of relevant Pi3K-based therapeutic combination(s) was not supported, by the presence of actual molecular abnormalities, nor by physician therapeutic practices, but by the identification of predictive markers of resistance to Pi3K-based monotherapies.”

In summary, the researchers conclude that their study demonstrates that inhibiting both mTORC1 and PLK1 proteins induces synergistic antitumor activity in multiple models of NSCLC. In the discussion section of this paper, the authors detailed the divergent methodology they used to come to their conclusion.

“This methodology may promote more relevant clinical trials and avoid non-efficient combinations, inacceptable toxicities, and expensive and time-consuming studies.”

Click here to read the full research paper, published by Oncotarget.

Read the press release here

YOU MAY ALSO LIKE: More Oncotarget Videos on LabTube

—

For media inquiries, please contact media@impactjournals.com.

Oncotarget

Trending With Impact: Promising Non-Small Cell Lung Cancer Prodrug

August 26, 2021

Researchers examined the preclinical prodrug LP-184 and its efficacy in treating non-small cell lung cancers that lack actionable targets or resistance-related genes.

—

Listen to an audio version of this article

Between 20 and 40% of adults with non-small cell lung cancer (NSCLC) eventually go on to develop brain metastases. Over 40% of patients with NSCLC have limited treatment options due to a lack of actionable therapeutic targets. Treatment for such patients has been limited to non-targeted chemotherapy—an approach which increases the risk of developing drug-resistance due to underlying resistance-associated mutations.

“Newer drugs that will be more potent and remain efficacious in NSCLC with such mutations could lead to better alternate or combinatorial therapies.”

Lantern Pharma (a pharmaceutical company developing targeted cancer therapies) created a new drug candidate and next generation member of the acylfulvene class of prodrugs, named LP-184. Researchers from Lantern Pharma and REPROCELL (a commercial contract research organization) conducted a study to test the anti-tumor activity of this preclinical compound in a variety of NSCLC cell lines. In 2021, Oncotarget published team’s pape, entitled, “The acylfulvene alkylating agent, LP-184, retains nanomolar potency in non-small cell lung cancer carrying otherwise therapy-refractory mutations.”

The Study

Despite LP-184’s highly-synthetic sounding name, the lead product in this acylfulvene prodrug (Illudins) is derived from, you guessed it, Jack-o-Lantern mushrooms.

“Acylfulvenes have been derived from cytotoxic agents called Illudins, isolated from Jack-o-Lantern mushroom (Omphalotus illudens), that retain and improve the cytotoxicity of parent Illudins for use as anticancer agents.”

The anti-tumor activity of this compound is based on activation through reductive mechanisms, mediated by enzymes such as Prostaglandin Reductase 1 (PTGR1). PTGR1 is known to be upregulated in some tumors, including in tumors with mutations in KEAP1. LP-184 sensitivity was investigated in NSCLC cell lines with individual or combined mutations in KEAP1, KRAS, TP53, and STK11.

“There is a high unmet need for effective therapies for NSCLC harboring mutations in these genes that have not only been considered undruggable till date but also are associated with loss of efficacy or resistance to multiple therapeutic strategies, at least in frontline regimens.”

The researchers tested LP-184 in vitro in 19 primary and metastatic NSCLC cell lines to determine the range of NSCLC settings that this compound might work best in. Clinical data analyses were also conducted by the researchers to predict tumor responsiveness to LP-184. In addition, the compound was examined in two mouse models of primary lung cancer. Mouse models were tested for sensitivity to LP-184 in both two- and three-dimensional culture systems.

“We sought to assess LP-184 activity in a panel of selected NSCLC adenocarcinoma cell lines, determine associations between genomic and transcriptomic profiles and responses of cell lines tested, and compare in vitro potency of LP-184 with that of approved chemotherapy agents.”

Conclusion

Among their many findings, the researchers demonstrated that LP-184 has high nanomolar potency in 11 of the 19 NSCLC cell lines tested—indicating broad NSCLC anti-tumor activity. In vivo, LP-184 showed efficacy in terms of tumor regression in one of the two mouse models.

“We propose further evaluation of LP-184 in multiple PTGR1 high NSCLC settings that may not necessarily be mutually exclusive, including in highly prevalent KEAP1 and KRAS mutant tumors (Figure 6), and in patients with lack of actionable targets or resistance-related genes with no effective therapy options available.”

Click here to read the full research paper, published by Oncotarget.

YOU MAY ALSO LIKE: More Oncotarget Videos on LabTube

—

For media inquiries, please contact media@impactjournals.com.

Oncotarget

Captain of Team Open Access Rides Again for Cancer Research

August 18, 2021

For the past four summers, Impact Journals has sponsored Team Open Access in the Ride for Roswell. The peloton has been captained by Sergei Kurenov, who is the Director of Surgical Simulation at Roswell Park Comprehensive Cancer Center — one of the leading cancer treatment and research centers in the nation. This year, Team Open Access was one of the many teams that participated to raise more than $5 million to help find a cure for cancer.

Prior to the 2021 Ride for Roswell (#RFR21) on August 7, we asked Sergei for his thoughts on the experience and motivation for riding.

Please tell us how you got started in the Ride for Roswell event and what pushes you to participate each year.

Kurenov: When I started working at Roswell Park Comprehensive Cancer Center, I saw how enthusiastically people supported this event and made a lot of contributions of their time in fundraising, patient care support, and cancer research. I wanted to be a part of this community.

This will be your fourth year as team captain and sixth year participating in the Ride for Roswell. What has been your most memorable year or moment since you’ve started?

Kurenov: My first year of the Ride is the most memorable. More than a few thousand riders performed the National Anthem. Then, all the riders cheered on the cancer survivors, reminding us of exactly why we participate.

During last year’s Summer of the Ride, you were a part of over 600 teams that rode to raise more than $3.6 million in the fight against cancer amid a global pandemic. Looking back, how has that specific Ride impacted your outlook on this year’s event and cancer research?

Kurenov: The pandemic has highly affected cancer research. Physicians and researchers are working very hard to minimize pandemic impact and get life back to normal for our patients.

This year, we already raised [more than] $5 million, which will be provided to the development of cancer treatments and cancer research.

Sponsored by Impact Journals, Team Open Access is once again captained by Sergei Kurenov who explains his motivation to participate in the Ride for Roswell. — (Photo Courtesy of Roswell Park Comprehensive Cancer Center)

Tell us a little bit about the 2021 Open Access team.

Kurenov: The 2021 Open Access team has grown again and now we have nine team members, ranging in ages from 13 to 65. Most of the members are scientists in the cancer research field.

Who is the fastest team member? The longest tenured teammate of yours? And, why do you think you make the perfect captain for this team?

Kurenov: Andrei is a great rider and I believe he is the fastest team member.

Liliya and Elena are the longest-tenured teammates for the last six years. They provide a tremendous help in the fundraising and in team organizing. They are also great photographers, making memorable images during the Ride. Each year, they create special Open Access team t-shirts which we are proud to wear during the Ride.

Who, or what, will you be focusing on as team captain this time around?

Kurenov: This year, Sofia joined the Open Access team. She is 13 years old and wants to ride 10 miles. Sofia and the rest of our team will ride together. Perhaps I will join the team or will have a barbecue for the whole team to celebrate afterwards.

How do you generally celebrate following the Ride?

Kurenov: After the Ride, all team members and many of our friends from Buffalo are planning to join a barbecue party in our backyard. Everyone is very welcome to the party.

Please give us your best pitch for people to start or continue donating to cancer research.

Kurenov: Earlier this year, I lost a very close friend who had fought against cancer for the last 17 years. When he was diagnosed, doctors predicted around 10 years of his survival after the initial treatment. However, thanks to the cancer research and new treatment developments in oncology, he almost doubled the doctors’ predictions. And, until this year, he lived a full life, working on cancer research, organizing scientific conferences, traveling around the world and making great photographs. His example shows that the constant cancer research and new technologies can help oncological patients. So, please continue donating to cancer research. This certainly will help to cure cancer more efficiently and save more lives.

Just like we requested of you last year, give us your best pitch for folks to join Team Open Access in 2022.

Kurenov: I am proud to announce that our team is supported again by Impact Journals – which publishes open-source, cancer-related scientific journals Oncotarget, Aging, Genes & Cancer and Oncoscience. These journals include high-impact research papers of general interest and biological significance in all fields of cancer research. As an example, I would like to mention the studies published by Impact Journals that cycling is linked to a substantial decrease in the risk of developing and dying from cancer or heart disease.

Join our team and help us reach our goal or donate to our efforts! No matter how you choose to support us, YOU are making a difference in the lives of the thousands of patients who turn to Roswell Park Comprehensive Cancer Center for hope each year.

Click here to learn more about the Ride for Roswell.

YOU MAY ALSO LIKE: More Oncotarget Videos on LabTube

—

For media inquiries, please contact media@impactjournals.com.

Oncotarget

Trending With Impact: Analysis of Breast Cancer in Nigerian Women

August 16, 2021

In this trending paper published by Oncotarget in 2021, a cohort of Nigerian women were assessed for a useful biomarker in aggressive molecular subtypes of breast cancer.

—

Listen to an audio version of this article

Forms of cancer can vary in prevalence and aggression in different populations of people around the world. For instance, incidence rates of breast cancer (BC) have been rising in Africa over the past few decades. Research finds that Nigerian women have the highest age-standardized mortality rate of breast cancer on the African continent. This population in particular also faces disproportionately aggressive molecular subtypes of breast cancer.

“BC in Nigeria is characterized by disproportionately aggressive molecular subtypes, with exceptionally high rates of triple-negative (TN) BC [4], similar to BC in other countries in West Africa [5] and among African American women in the United States [6].”

In order to develop better treatment strategies, there is a distinct need to identify biomarkers that indicate, and even predict, these aggressive subtypes of breast cancer in Nigerian women. In 2021, a new study was conducted by researchers from Duke University, University of Lagos, Obafemi Awolowo University Teaching Hospital, University of Ibadan, Federal Medical Center Abeokuta, UNC Gillings School of Global Public Health, Our Lady of Apostle Catholic Hospital in Ibadan, University of Alabama at Birmingham, University of Kentucky, and University of Kansas Medical Center. Their trending research paper was published by Oncotarget and entitled, “Association of high-sensitivity C-reactive protein and odds of breast cancer by molecular subtype: analysis of the MEND study.”

C-Reactive Protein

“C-reactive protein (CRP) is associated with risk and aggressiveness for several types of cancer.”

When there is inflammation in the body, levels of the C-reactive protein (CRP) increase. This easily measurable protein can be a useful biomarker of systemic inflammation, infection, or tissue damage. Previous studies show that circulating CRP has been elevated in various types of cancers; it has also been associated with tumor prognosis. Past studies about CRP’s association in breast cancer subtypes have been notably few, and none have focused on isolating subpopulations in Africa.

“Additionally, it is worth noting that most of these past studies have been conducted in populations from the United States and Europe, among mostly White study populations, and to our knowledge, none have been conducted in populations from Africa.”

The Study

In this study, 555 Nigerian participants were assembled—of which 296 were confirmed breast cancer cases, and 259 were controls. The researchers collected clinical and reproductive characteristics of each participant, including the controls. In their first analysis, the researchers observed that newly diagnosed cases of Nigerian breast cancer were significantly more likely to have high levels of highly-sensitive CRP (hsCRP) compared to the controls. After adjusting for socio-demographic, clinical, and reproductive variables, the team still observed significant statistical significance for high levels of hsCRP associated with Nigerian BC. The findings from this cohort study also showed that high hsCRP was associated with a four-fold increased odds of BC.

“We also provide novel evidence of associations between hsCRP and BC molecular subtypes, with significant associations observed for luminal A, TN, and HER-enriched subtypes.”

Conclusion

“In conclusion, our analysis revealed a positive association between hsCRP and odds of BC, overall and for all molecular subtypes. Because CRP is an easily measured biomarker in the blood, it may represent a useful predictor of BC in the Nigerian context. We urge larger studies, preferably prospective cohort studies, among women of African descent to further characterize this association.”

Click here to read the full research paper, published by Oncotarget.

YOU MAY ALSO LIKE: More Oncotarget Videos on LabTube

—

For media inquiries, please contact media@impactjournals.com.

Oncotarget

The Ride for Roswell: Rolling Around The Track August 7

July 28, 2021

Listen to an audio version of this article

The Ride for Roswell is one of the nation’s largest cycling events—hosted by Roswell Park Comprehensive Cancer Center—with ambitious goals 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 25 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.

The Origin of The Ride

The Ride for Roswell started in 1989, when Mitch Flynn, owner of the advertising agency Flynn & Friends, met Katherine Gioia. Katherine was a four-year-old patient battling a rare form of cancer. After Katherine’s death, less than a year after her diagnosis, Katherine’s mother, Anne Gioia, and aunt, Donna Gioia, founded the Roswell Park Alliance Foundation in her memory to raise money for cancer research and treatment. On June 29, 1996, Mitch and Alliance Foundation staff launched the first Ride for Roswell.

In the 25 years since then, thanks to many thousands of riders and generous donations, the Ride for Roswell has raised over $60 million to fund cancer research. The event has become one of the largest single-day charity rides in the United States.

This Year

Traditionally (excluding last year’s COVID-19 inspired “Summer of The Ride”), teams of bicyclists register to ride in a one-day event and raise money to support their participation. This summer, there are two ways to ride. Riders can join in-person at various locations (socially distanced) throughout the Western New York area on Saturday, August 7, 2021. Participants can also ride on their own throughout the month of August.

Impact Journals has been sponsoring the Ride for Roswell since 2018. The Impact Journals peloton, Team Open Access (named after the open-source online medical journals Oncotarget, Aging, Genes & Cancer, and Oncoscience), is captained by Sergei Kurenov. Sergei (who has been riding in the event since 2016) works at the Roswell Park Comprehensive Cancer Center to create, develop, and implement innovative diagnostic and surgical pre-planning software used in cancer treatment.

“Roswell Park Comprehensive Cancer Center is dedicated to providing a high level of care for cancer patients,” Sergei said. “By contributing to the Ride for Roswell, we are helping our patients to fight this most dangerous disease.”

Join Us!

There is still time to join Team Open Access and the Ride for Roswell this summer. You can also support the team by giving a donation of any size. Any avenue of support you may choose to donate to the Ride for Roswell will make a difference and change lives.

“Finding a cure for cancer is something we are all incredibly passionate about, and we are so thankful and grateful for your support,” Sergei said. “Together, we can make a difference!”

Visit our team page to join or donate today.

Click here to learn more about the Ride for Roswell.

YOU MAY ALSO LIKE: More Oncotarget Videos on LabTube

For media inquiries, please contact media@impactjournals.com.

Oncotarget

Oncotarget Uses TrendMD to Expand Research Impact

July 15, 2021

Oncotarget began using TrendMD—a platform that recommends relevant content to a large network of research readers.

Listen to an audio version of this article

Oncotarget has started a new venture to expand our reach and connect with other relevant platforms using TrendMD. The TrendMD widget has been applied at the bottom of all research papers on Oncotarget.com to serve recommended content to our readers, and readers on thousands of other high-traffic websites and scholarly platforms. Recommended content is based on the content currently being viewed, content that has been viewed in the past, and content other similar readers are viewing.

“[TrendMD’s] recommendation algorithms continuously optimize the placements of links to your content for the right audience while readers are actively looking for something interesting to discover.” —Source: TrendMD.com

This platform uses algorithms similar to those that Amazon uses to help bring fresh new relevant content to interested readers. The TrendMD widget recommends content both derived from Oncotarget.com and from other biomedical journals and articles publishing similar content. They also use collaborative filtering and track user behavior to learn how to suggest the right content for the right people.

Oncotarget uses TrendMD to help our authors better circulate their research to targeted audiences around the world, cross-promote papers in adjacent fields, and increase paper citations. In a research study by Scientometrics, TrendMD was shown to outperform PubMed related citations by 272%. By joining this platform, Oncotarget publications are now incorporated into the TrendMD network—with 100 million total monthly users. Papers published by Oncotarget will now be recommended on hundreds of other leading peer-reviewed journals and scholarly websites.

“TrendMD is the world’s leading discovery platform, delivering over 1 billion recommendations to over 100 million unique users each month on 4,500 websites from over 300 scholarly publishers.” —Source: TrendMD.com

Since papers are recommended based on algorithms aiming to share specific content with readers who are most likely to be interested in the content, readership and engagement on TrendMD is very high. TrendMD statistics show that readers have the lowest bounce rate and view more content on TrendMD compared to Google AdWords, Google Scholar, Twitter, and PubPeer. Oncotarget is proud to offer this service for our authors and the scientific research community.

Click here to learn more about TrendMD.

YOU MAY ALSO LIKE: More Oncotarget Videos on LabTube
—
Oncotarget is a unique platform designed to house scientific studies in a journal format that is available for anyone to read—without a paywall making access more difficult. This means information that has the potential to benefit our societies from the inside out can be shared with friends, neighbors, colleagues, and other researchers, far and wide.

For media inquiries, please contact media@impactjournals.com.

Oncotarget

Trending With Impact: Targeted Treatment for Recurrent Ovarian Cancer

July 15, 2021

In this 2018 paper, researchers studied a new targeted strategy to treat ovarian cancer.

Anatomy and physiology of Ovary under the microscopic in laboratory.

—

Listen to an audio version of this article

Sialyl-Thomsen-nouveau (STn)—a tumor stem cell-associated carbohydrate antigen—is a moiety. “Moiety” is a term used to name molecular particles identified among multiple types of molecules. STns have been found on protein markers of cancer stem cells (CSCs) in pancreatic, colon, and gastric malignancies. Researchers hypothesize that CSCs can survive adjuvant chemotherapy and are responsible for tumor resurgence in many cancers, including recurrent ovarian cancer (OvCa).

“Unfortunately, despite aggressive surgery and adjuvant chemotherapy, most women with OvCa develop recurrent disease that is ineffectively treated with current therapies. Novel treatment strategies are urgently needed to target chemoresistant disease.”

Researchers from Massachusetts General Hospital, Siamab Therapeutics, Inc., and Harvard Medical School conducted a novel research study in 2018 and authored a paper published by Oncotarget, entitled, “Treatment of ovarian cancer by targeting the tumor stem cell-associated carbohydrate antigen, Sialyl-Thomsen-nouveau.”

“Accumulating research has revealed not only the importance of CSCs in tumor initiation, metastasis, recurrence, and chemoresistance, but also the potential of CSC-directed therapies to impact patient survival.”

The Study

Researchers often use CD133 (a cell surface antigen) as a marker to detect and sequester CSCs in various solid tumors. In this study, the team analyzed the expression of STn and CD133 in ovarian cancer cell lines, their colony and sphere formation capacity, response to cytotoxic chemotherapy, and STn’s response to two targeted antibody drug conjugate (anti-STn-ADC) treatments in vivo and in vitro.

“Analyses of colony and sphere forming capacity and of response to standard-of-care cytotoxic therapy suggest a subset of OvCa STn+ cells display some CSC features.”

In a subset of human OvCa cell lines, the researchers found that STn and CD133 were co-expressed. They also found that STn+ and CD133+ cells have increased colony formation capacity and elevated levels of STn increases sphere formation. Both of the anti-STn-ADC treatments had anti-cancer effects in the OvCa cell lines in vivo and in vitro. These findings show that STn demonstrates some stem-like properties and may be a viable therapeutic target in ovarian cancer.

“In summary, STn+ cells demonstrate some stem-like properties and specific therapeutic targeting of STn in ovarian tumors may be an effective clinical strategy to eliminate both STn+ CSC and STn+ non-CSC populations.”

Conclusion

“Our finding that targeting STn+ cells in vivo with a highly specific antibody conjugated to auristatin resulted in marked decreases in tumor burden without any obvious toxicity suggests that an anti-STn ADC approach may serve as a viable option in eliminating non-CSC as well as some CSC populations.”

Click here to read the full scientific study, published by Oncotarget.

Oncotarget

Trending With Impact: ONC201 Induces Apoptosis in Breast Cancer

July 1, 2021

A novel therapeutic combination converts anti-proliferative effects in breast cancer cells to pro-apoptotic.

Trending With Impact: ONC201 Induces Apoptosis in Breast Cancer — 3D illustration of the stages of cell apoptosis.

The Trending with Impact series highlights Oncotarget publications attracting higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Oncotarget.com.

—

In the 1990s, Dr. Wafik El-Deiry’s cancer research laboratory discovered a gene that encodes a protein, called death receptor 5, or TRAIL receptor 2. TRAIL is a protein that induces the process of cell death, or apoptosis. This pathway activates the body’s innate immune system and is capable of suppressing cancer cells by inducing apoptosis.

After this discovery, researchers from the same lab considered the notion that increasing the production of TRAIL to enhance the body’s own immune response may have a safe therapeutic benefit in the treatment of cancer. The team searched for small molecules capable of upregulating the TRAIL gene and discovered the therapeutic compound TIC10, also known as ONC201. ONC201 is a well-tolerated drug currently being evaluated in advanced clinical trials for the treatment of various malignant solid tumors, including refractory metastatic breast cancer.

Researchers in Dr. El-Deiry’s laboratory have continued to investigate this drug in order to learn more about how it works, and what tactics or combinations may be used to produce better results for cancer patients. In a 2016 study, the researchers learned that ONC201 produces heterogeneous results in different tumor types.

“The question is, with this specific drug, what is the pattern of response, what determines that, and how can we get it to work a little bit better,” Dr. El-Deiry said in a recent Oncotarget interview.

Based out of Temple University, Fox Chase Cancer Center, Brown University, and the El-Deiry Cancer Research Laboratory, researchers wrote a paper detailing their latest study on ONC201. The paper was published by Oncotarget in 2020 and entitled, “TRAIL receptor agonists convert the response of breast cancer cells to ONC201 from anti-proliferative to apoptotic.”

THE STUDY

Led by first-author Dr. Marie Ralff, the researchers in this study found that ONC201 induces differential responses across various breast cancer tumor subtypes. Few breast cancers are responsive to TRAIL, and one subtype that is responsive to TRAIL is triple-negative breast cancer.

“We saw that in some of these tumor types (the triple-negative breast cancer type in particular) the compound was having a pro-apoptotic effect, and in other [breast cancer] tumor types, it was having an anti-proliferative effect,” said Dr. Ralff.

When comparing in vivo and in vitro results of the drug, the team found that the pro-apoptotic effects translated to efficacy, while the anti-proliferative effects did not. The researchers then decided to investigate strategies to convert breast cancer cell response to ONC201 from anti-proliferative to apoptotic. ONC201 affects two known mechanisms of TRAIL resistance in breast cancer: death receptor 5 and anti-apoptotic proteins. This fact led the researchers to introduce a TRAIL receptor agonist antibody in combination with ONC201.

“If we pretreat TRAIL resistant breast cancer cells with ONC201, the level of surface death receptor 5 goes up and the intracellular levels of anti-apoptotic proteins go down, thereby priming the cells to undergo death through the TRAIL pathway. So, if we then add in a TRAIL receptor agonist, it induces apoptosis in a very potent way,” Dr. Ralff said.

CONCLUSION

“The concept is when cells are treated with the small molecule compound, not a whole lot happens. When cells are treated with TRAIL, not a whole lot happens. When you put them together, it’s like flipping a switch. The cells now undergo potent cell death,” Dr. El-Deiry said.

The potential efficacy of this therapeutic combination was strengthened by results in the study showing that ONC201 paired with the TRAIL receptor agonist antibodies is non-toxic to fibroblasts. The researchers also showed that the natural killer cells are only active against the breast cancer cells that have been exposed to ONC201. In vivo studies reaffirmed the safety of this combination in mouse models.

Click here to read the full research study, published by Oncotarget.

—

For media inquiries, please contact media@impactjournals.com.