Thorough Genotyping and Repurposed Drugs Key to Treating Small-Cell Lung Cancer, says Cancer Expert

Cancer expert Antonio Giordano, MD, PhD, Director of the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University, describes the recent progress and future possibilities of treating SCLC. Giordano was recently quoted in the Italian news outlet Il Mattino

Newswise — Small cell lung cancer (SCLC) is an aggressive disease characterized by quick growth and spread. While there has been a gradual decrease in incidence of SCLC in recent years, likely reflecting the decreased prevalence of tobacco use, little progress has been made in treating SCLC due to its complex pathogenesis.

The majority of patients, including those with limited-stage disease and those who initially respond to chemo- and radiation- therapy (two traditional pillars of cancer therapy), become resistant to treatment resulting in a very small percentage (approximately 6%) who survive 5 years after being diagnosed.

Smoking is the main risk factor for SCLC, with only 2-3% of patients categorized as never-smokers.

Identifying Therapeutic Targets in Small-Cell Lung Cancer

From the molecular point of view, SCLC is characterized by a multitude of alterations, owing to the fact that cells are exposed to a myriad of carcinogens contained in cigarette smoke, which bind and mutate DNA. These alterations affect numerous genes and pathways, but among these there are few obvious therapeutic targets. This means that the driver genes responsible for most SCLC development and progression have yet to be identified with any certainty.

However, new high-throughput technologies, which allow comprehensive gene profiling, have revealed promising findings. For example, 20% of SCLC patient tumors bear alterations in the MYC gene family. This discovery has helped to identify a subset of patients sensitive to an oncogenic kinase downstream in the MYC pathway, allowing for better designed, biomarker-driven clinical trials for these, often repurposed, therapeutic agents.

Similarly, PARP1 and Notch have been found overexpressed in SCLC. In order to target PARP1, an enzyme which, when it malfunctions, leads to replication of damaged DNA, researchers are currently evaluating the efficacy of PARP inhibitors for treatment of SCLC. And, to investigate targeting of the Notch signaling pathway, which influences the cellular life-cycle, the FDA is in the process of approving Tarextumab, a selective Notch inhibitor, in the treatment of SCLC.

Another issue with SCLC tumors is that they are mostly characterized by the loss of two crucial oncosuppressor genes, named RB, RB2\p130 i and TP53, which are less actionable pharmaceutically because it is much more difficult to restore a loss of function rather than block an oncogenic gain of function. Although challenging, researchers are nonetheless trying to develop strategies in this direction.

Repurposing Existing Drugs

Also important to the progress of SCLC therapies, more effective drug identification and testing, through the use of powerful mouse models of the human disease, put researchers in a good position to tackle this cancer type and attempt better defined targeted approaches.

Recent immunotherapy approaches have emerged as a significant new pillar in cancer therapy and are being assessed in numerous clinical trials for a multitude of tumors, including SCLC. In particular, two new agents, nivolumab and ipilimumab, have recently been developed to treat other forms of cancer, such as unresectable or metastatic malignant melanoma, advanced non-small-cell lung cancer (NSCLC), and advanced renal-cell carcinoma. These agents have also been tested for applications in SCLC. Nivolumab and ipilimumab are constituted by monoclonal antibodies functioning through direct inhibition of CTLA4 and PD1, respectively, which are key negative regulators of the antitumoral immune function. Bristol-Myers Squibb (BMS) was able to obtain the National Comprehensive Cancer Network indication for use of nivolumab and nivolumab plus ipilimumab in patients with SCLC who progressed after one or more previous regimens. The indication was achieved upon the publication on Lancet Oncology by Scott Antonia and colleagues, who reported the efficacy of nivolumab monotherapy and nivolumab plus ipilimumab, achieving antitumour activity with durable responses and manageable safety profiles in previously treated SCLC patients, enrolled in the CheckMate-032 clinical trial.

Data was also presented at the World Lung Cancer Congress on the immunotherapy drug pembrolizumab, another therapeutic antibody against PD1, already approved for other diseases, which showed good efficacy.

One additional drug in this category is rovalptizumab teserine, a first-in-class antibody-drug conjugate comprised of a humanized monoclonal antibody against DLL3 and a toxin. DLL3 is a Notch ligand found to be expressed on 80% of SCLC. There is a 3rd line trial which is biomarker driven, meaning that they test for DLL3 expression and patients are eligible if they have “high” DLL3.

In conclusion, with careful evaluation, a doctor can use immunotherapy as a second phase or combination therapy, but many factors should be considered. For example, the issue of whether a patient should have some time to recover after a course of chemotherapy before starting immunotherapy is still debated among colleagues. Also, some combinations, such as nivolumab plus ipilimumab, seem to work better but can be more toxic.

About the Expert

Antonio Giordano, MD, PhD, Director of the Sbarro Institute for Cancer Research and Molecular Medicine and Center of Biotechnology, College of Science and Technology, Temple University and Professor of Pathology at the University of Siena, Italy

About Sbarro Health Research Organization

Sbarro Health Research Organization conducts research in cancer, diabetes, and cardiovascular disease. Based in Philadelphia, Pennsylvania on the campus of Temple University, our programs train young scientists from around the globe.

Newswise Release

Sbarro Health Research Organization President Re-Elected to Board of Italian American Foundation

Dr. Giordano is joined on the board by Corporation for Public Broadcasting President and CEO Patricia de Stacy Harrison and former Talk America President, Chairman and CEO Gabriel A. Battista who will serve as co-chairperson of the Foundation

The National Italian American Foundation (NIAF) met this week to elect its Board of Directors for the 2017-2021 term. Board members for the new term will include re-elected member Antonio Giordano, president and founder of the Sbarro Health Research Organization (SHRO) at Temple University in Philadelphia, who has served on the Board since 2011.

“It has been an honor working with NIAF,” says Dr. Giordano, “especially in creating our annual medical research conference highlighting the contribution of Italian-Americans to science.” The conference, a collaboration of the NIAF and SHRO, is held each October, and includes the presentation of the annual Giovan Giacomo Giordano NIAF Lifetime Achievement Award for Ethics and Creativity in Medical Research.

Giordano serves with newly elected co-Chairpersons Patricia de Stacy Harrison, president and ceo of the Corporation for Public Broadcasting, and Gabriel A. Battista, former president, chairman, and CEO of Talk America.

“Certainly our new co-Chairs have some big shoes to fill, but I’m very excited for the opportunity to work with two of the most dedicated Italian Americans I’ve come to know during my time at the Foundation. Pat and Gabe have been tireless advocates for our community for so many years and I really look forward to the next phase of the NIAF story under their leadership,” said NIAF President and COO John M. Viola.

Giordano is proud to serve on the NIAF Board of Directors, continuing a lifelong mission of service to the Italian-American community. The Sbarro Health Research Organization began with a mission to foster international research collaboration with Italian and American scientists.

“I look forward to promoting the work of NIAF among my colleagues at the top Italian and American universities, to make our mission known among the next generation of Italian-American scientists,” says Dr. Giordano.

The NIAF Board of Directors includes other Italian-Americans from a wide variety of fields in the public and private sector, including a former Major League Baseball player; an executive vice president at the Wildlife Conservation Society; a venture capitalist; and an executive in higher education. More information about the NIAF and the newly elected Board of Directors can be found at www.niaf.org.

About the National Italian American Foundation
The National Italian American Foundation (NIAF) is a non-profit, non-partisan organization dedicated to preserving, promoting and protecting the Italian American heritage and culture. To learn more about the Foundation and become a member, please visit www.niaf.org.

About the Sbarro Health Research Organization
The Sbarro Health Research Organization (SHRO) is non-profit charity committed to funding excellence in basic genetic research to cure and diagnose cancer, cardiovascular diseases, diabetes and other chronic illnesses and to foster the training of young doctors in a spirit of professionalism and humanism. To learn more about the SHRO please visit www.shro.org

Original Newswise  Release

Economic Disparities a Growing Concern for Cancer Diagnosis and Treatment

The most recent global cancer data from the WHO highlights the growing differences in mortality rate among regions of the world bearing very different economic circumstances. Given that cancer has been globally responsible for the death of 8.8 million individuals in 2015 and that the number of new cases is expected to rise by about 70% over the next two decades, these new figures are cause for concern looking at the rise of Cancer among economically weak regions.

See the WHO Cancer fact sheet, updated in February 2017, here.

In fact, according to the most recent reports, about 70% of deaths from cancer occur in low and middle-income countries. Furthermore, only 35% of low income countries carry pathology services generally available to the public sector while treatment services are available in less than 30% of low income countries as compared to 90% of high income countries.

“It is not surprising that only one in five of these low- and middle-income countries have the necessary data to drive cancer policies and health interventions,” comments Prof. Antonio Giordano, Director of Sbarro Health Research Organization, a cancer and biomedical research institute based in Philadelphia.

“This problem,” adds prof. Giordano, “is a major driver for the expected increase of cancer cases and deaths, especially among children and children-bearing women in these countries also due to the higher risk connected to specific infective agents for which there are no widespread prevention programs as well as limited access for women and children to what we now consider basic care in other parts of the world.”

“The Limited access to sustainable diagnosis and treatment in economically weak regions disclosed by these reports,” states prof. Pierluigi Scalia, director of ISOPROG Onlus, an Italian non profit research organization, “is not only restricted to third world countries, but it is likely to be witnessed within countries with higher income when comparing different regions of the same country.” “For example,” says prof. Scalia, “we could expect the same trend due to lack of access to basic sustainable care when comparing large cities to the peripheries such it can be seen throughout the US and as it is still a problem in countries like Italy between the northern and the southern regions. In all these cases, the incidence of cancer in children and economically weak part of our society is expected to rise.”

“Research as well as new social entrepreneurial models to manage healthcare,” concludes prof. Giordano, “are desperately needed to face this growing problem.”

NewsWise Release

 

Actors with Disabilities Go to Hollywood Festival, Sbarro Health Research Organization Praises Filmmakers

The Sbarro Health Research Organization at Temple University, under the direction of Dr. Antonio Giordano, usually collaborates with Italian scientists working both in the U.S. and Italy. But today, the organization is praising a group of Italian filmmakers for their contribution to medicine through the arts. Their film, Ho Amici In Paradiso [I Have Friends in Heaven], will screen this week at the Los Angeles Italia Film, Fashion, and Art Fest.

I Have Friends in Heaven is a great achievement in the honest and sympathetic portrayal of people with disabilities,” Dr. Giordano said. “The Sbarro Health Research Organization at Temple University is very interested in participating in research and assisting people with a cognitive impairment, intellectual disability, and mental illness.”

Director Fabrizio Cortese’s film tells the story of a troubled man who finds meaning in life after working with the disabled at the Opera Don Guanella, a Catholic Servants of Charity organization serving people with disabilities in Rome.

After screening at the Rome International Film Festival in 2016 and gaining recognition from Pope Francis, the film will screen at the Hollywood TCL Chinese Theater on February 22. Director Fabrizio Maria Cortese will attend, along with Michele Iannaccone and Stefano Scarfini, two of the disabled actors from the Center who performed in the film.

The festival is supported by the Italian Consulate in Los Angeles to promote Italian excellence in the arts.

Also in attendance will be producer Antonio Maria Cortese, and a delegation from the ‘Opera Don Guanella’ rehabilitation center in Rome, including the Chief of Casa San Giuseppe Don Pino Venerito, and medical director Simonetta Magari. The rest of the cast included five other disabled actors from the Opera Don Guanella, as well as veterans of Italian stage and screen Valentina Cervi, Fabrizio Ferracane, Antonio Catania, Antonio Folletto, Enzo Salvi and Emanuela Garuccio.

Synopsis of the Film
Felice Castriota is an impulsive and superficial person who lives in the South of Italy as an accountant. Both his recklessness and greed for money bring him to tighten ties with crime. One day he is discovered. The State’s attorney of Lecce proposes assignment as a social worker to Felice as an alternative to jail. At Centro Don Guanella, a Catholic charity for the disabled, everything changes. In fact, he gains awareness about his mistakes and the important things in life, thanks to the entire group of disabled people he encounters during his amazing rehabilitation path.

SEE ORIGINAL STUDY

See NewWise Release

Micro-RNA May Amplify Effectiveness of Sorafenib in Difficult Liver Cancer Cases

Treatment options for liver cancer are often limited and almost exclusively involve transplantation if possible, or local chemoembolization and radiofrequency ablation. Medical treatments for more advanced stages have been explored during recent decades, but only the drug sorafenib, a small molecule multi-kinase inhibitor, has shown promising results and been approved for use by international medical agencies. Unfortunately, only 25% of patients respond to sorafenib treatment, so researchers have endeavored to understand its mechanism of action and discover a way to boost its effectiveness.

A recent study, published in the journal Journal of Cellular Physiology, describes further scientific insight into the involvement of a small non coding RNA, miR-125a, in the anti-cancer effects of sorafenib in the treatment of liver cancer, or hepatocellular carcinoma. These results are interesting as miRNAs have multiple available intracellular targets and could contribute to the amplification of the effects of sorafenib.

The link between small kinase inhibitors such as sorafenib, and the existing molecular pathways that govern cell proliferation such as miR-125a, may be useful to potentiate the anticancer activity of sorafenib. Clinical applications of this knowledge might seek to identify and increase the number of liver cancer patients that respond positively to the drug.

The study includes work done by Prof. Michele Caraglia and Aniello Russo, of the University of Campania “L. Vanvitelli” in Naples, and Caserta, Italy, in collaboration with Prof. Antonio Giordano, Director of the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University in Philadelphia.

“Sorafenib is still the only drug indicated in the treatment of hepatocellular carcinoma, which highlights the difficulty in the medical treatment of liver cancer,” says Prof. Antonio Giordano. “Sorafenib is effective because it acts upon multiple intracellular targets and interferes with both cancer proliferation and tumor blood supply. However, its activity is limited to only 25% of patients that are sensitive to its effects. This strongly pushes the researchers to define the mechanism of action of the drug,” Giordano concludes.

“MicroRNAs can act as either cancer-fighting tumor suppressors, or as cancer-causing oncogenes,” says Professor Michele Caraglia. “We have found that the expression of miR-125a is strongly involved in the mechanism of action of sorafenib and its ability to regulate cancer cell proliferation. These findings suggest the possible use in the future of miR125a in combination with sorafenib in order to potentiate the anti-cancer activity of the drug,” Caraglia concludes.

The study results open a new scenario of intervention in the treatment of hepatocellular carcinoma in which small molecules such as sorafenib can be used in association to nucleic acids such as miR-125a. The latter could be administered to patients systemically encapsulated in novel drug delivery options such as nanocarriers. Researchers plan to further study the in vivo efficacy of these strategies to increase treatment options for this difficult form of cancer.

NewsWise Release

Citations
Potenza N, Mosca N, Zappavigna S, Castiello F, Panella M, Ferri C, Vanacore D, Giordano A, Stiuso P, Caraglia M, Russo A. MicroRNA-125a-5p Is a Downstream Effector of Sorafenib in its Antiproliferative Activity Toward Human Hepatocellular Carcinoma Cells. J Cell Physiol. 2016 Dec 16. doi: 10.1002/jcp.25744.

PubMed Abstract                           J Cell Physiol Link

Every Diagnosis of Cancer Should Come with One of These, Says Cancer Expert

“Every cancer diagnosis should come with a referral to genetic counseling,” says cancer expert Dr. Antonio Giordano, President of the Sbarro Health Research Organization at Temple University.

Giordano’s comments come in response to a study published this week in JAMA, the journal of the American Medical Association, which showed signs that too few patients are getting genetic counseling. The study described a shortfall of genetic screening for breast cancer patients at risk for mutations of the BRCA1 and BRCA2 genes, with as many as 80% of patients surveyed said they wanted testing, but only about 40% received genetic counseling.

“Genetic counseling is so important,” says Dr. Giordano, “not only for BRCA, but for other testing as well. Sometimes there are incidental findings which can guide the medical oncologist to the right targeted approach. Such as, which hormonal therapies or chemotherapy agents will be most effective.”

The study also indicated a majority of patients surveyed say the reason they didn’t get a genetic screening was because the doctor didn’t recommend it to them.

“Most of the time, this may be because the medical oncologist feels they need to decide for the patient,” says Dr. Giordano, “and they may prescribe genetic counseling if they feel it is called for, but may not explain it to the patient.”

That may be a mistake that needs to change, says Dr. Giordano, for more reasons than just medical.

“Psychologically, it is very important for the patient to participate in decisions about their treatment. They are often scared, and to have more information can help them feel empowered in their medical decisions,” Dr. Giordano said. “It is beneficial for the patients’ overall well-being, as they deal with such a serious disease.”


About
Sbarro Health Research Organization conducts research in cancer, diabetes, and cardiovascular disease. Based in Philadelphia, Pennsylvania on the campus of Temple University, our programs train young scientists from around the globe.

Newswise release

How Red Pigmentation in Foods Helps Fight Lung Cancer

For those of you smokers, we aren’t saying you shouldn’t quit!  However, to help counteract some of the harmful effects of nicotine check out this article for the healing benefits of red pigmentation in certain foods.

https://m.medicalxpress.com/news/2017-01-red-pigment-peppers-oranges-linked.html

 

Researchers find BCX—red pigment abundant in sweet red peppers, paprika, winter and butternut squash, oranges, and tangerines, among other foods—appears to counteract nicotine’s ability to accelerate the growth of lung tumors. Credit: Ingimage

Great News Coffee Lovers!!

#Coffee is addictive but this just maybe one of the few good “drugs” to be addicted to, in moderation!  Did you know that drinking one cup of coffee a day can help lower your risk of diabetes, liver cancer, melanoma, and multiple sclerosis?  It can also help enhance memory, boost your mood, and this one you’ll never guess decrease tooth decay!!  So for all of my fellow coffee addicts out there drink up guilt-free!
#kimbo Kimbo

coffee.jpg

 

http://www.itechpost.com/articles/76352/20170120/why-every-guy-should-drink-coffee-discover-coffees-health-benefits.htm

Treating a cancer patient for a second time

In order to determine whether a growth represents relapse of a previously diagnosed cancer or is a newly developed, separate tumor, doctors obtain a tissue sample from the patient and have it examined by a pathologist.
#prevention #cancer #tumor

ccs-kidney-cf363-13-left

A tumor from a young boy’s kidney (a normal kidney tubule is visible top right).

http://blog.dana-farber.org/insight/2017/01/when-cancer-occurs-in-someone-who-has-already-been-treated-how-do-doctors-determine-whether-its-a-new-tumor-or-the-spread-of-the-earlier-tumor/