University of Pennsylvania

Philadelphia, Pennsylvania
Rhodes-Thompson Professor of Chemistry

Research

Dr. Smith combines his expertise in bioorganic chemistry, materials science, and natural products to synthesize complex anti-cancer drugs based upon naturally occurring products. Dr. Smith was the first to synthesize large- scale production of discodermolide, a compound found in a sea sponge. As an NFCR-funded scientist since 2016, his collaborative efforts with fellow NFCR scientist, Dr. Susan Horwitz, focus on synthesis of analogs similar to discodermolide but without its toxicity. Discodermolide acts similar to Taxol® but causes cancer cells to become senescent – a dormant cell state that can cause drug resistance and drive tumors to be more aggressive. Using multiple cutting-edge chemical and scientific techniques, Dr. Smith discovered the structural differences between discodermolide and an analog. Testing in Dr. Horwitz’s lab suggests the differences underlie the pro-cancer senescent effect. The discodermolide analogs developed by Drs. Smith and Horwitz have the potential to improve outcomes for patients with breast, ovarian and lung cancer.

Dr. Smith has recently developed viable synthesis of two additional natural anti-cancer products: 1) pterocidin – derived from bacteria and shown to lower progression of colon cancer and 2) neaumycin B – derived from a marine sponge and shown to be a potent anti-tumor agent for the difficult-to-treat brain cancer, glioblastoma or GBM. Dr. Smith’s synthesis of new anti-cancer agents with high potency to kill cancer and low propensity to induce senescence has the potential to greatly impact the outcomes for cancer patients.

Bio

Amos B. Smith III, Ph.D., received his Bachelor and Master’s degrees from Bucknell University and his Ph.D. from Rockefeller University, where he was also an associate from 1972-1973.

In addition to his fellowship with NFCR, Dr. Smith is a fellow of the American Academy of Arts and Sciences and member of the ESPCI ParisTech Scientific Council.

Dr. Smith’s laboratory has prepared more than 90 natural products possessing significant bioregulatory properties to date and his research achievements have been reported in more than 500 peer-reviewed publications. In 2015, Dr. Smith was awarded the Royal Society of Chemistry’s Perkin Prize for Organic Chemistry.

Related Content

The World’s First Oncolytic Virus Drug was Launched to Treat Malignant Brain Tumor GBM

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor in adults, with a median survival of only about ten months. Unlike low-grade gliomas (grades I and II), which grow slowly, high-grade gliomas (grades III and IV) grow much faster and can spread to other parts of the brain, resulting in a patient’s death. GBM is the highest grade brain tumor (grade IV) with a very poor prognosis. The standard treatment for GBM includes surgery, radiation, and chemotherapy. However, these limited treatment approaches cannot control the tumor progress, and the rate of brain tumor recurrence is high, resulting in low overall survival (OS) in most patients.   Oncolytic Virus Therapy  Oncolytic virus therapy represents a new promising cancer immunotherapy approach that utilizes genetically modified viruses to infect and kill cancer cells. The viruses are modified to selectively infect and lyse cancer cells through genetic engineering processes while leaving normal cells unharmed. The genetic modification of the viruses also grants them the ability to produce immune-boosting molecules or initiate anti-cancer immunity through multiple mechanisms of the patient’s own immune system.  The First Oncolytic Virus Therapy for GBM  Recently, the world’s first oncolytic virus-based immunotherapy (Teserpaturev) was approved in Japan. Teserpaturev offers a new option for treating GBM and brings new hope to thousands of patients suffering from this malignant brain tumor.  Teserpaturev is a genetically engineered herpes simplex virus type 1 (HSV-1). The uniqueness of this new oncolytic virus-based drug is that it not only has strong killing power to brain tumor cells that the virus entered into, but it is also able to kill the tumor cells that have spread to other parts of the brain. This process happens by inducing systemic antitumor immunity of a patient’s own immune system.  In June 2021, Teserpaturev received a conditional and time-limited marketing approval in Japan to treat malignant glioma based on a Japanese phase 2 clinical trial in patients with GBM. The clinical trial results showed that 92% of patients who received Teserpaturev immunotherapy treatment were still alive after one year. This percent is considerably higher than the typical 15% one-year survival rate in this group of patients receiving standard late-stage brain tumor treatments.  Bottom Line Because Teserpaturev is currently under conditional and time-limited marketing approval in Japan, this novel immunotherapy for GBM is only available at specified hospitals in Japan. We hope international multi-center clinical trials on this innovative drug can take place in the near future. Hopefully, the novel therapy can be made available to GBM patients around the world.  Stay up-to-date with the latest information on new drug development. Receive our monthly e-newsletter and blogs featuring stories of inspiration, support resources, cancer prevention tips, and more; sign up here.  Additional Reads You May Also Enjoy: Treating Brain Cancer: What You Need to Know New Brain Scan Technology Can Improve Tumor Removal GBM AGILE – Changing the Way We Fight Brain Cancer References Daiichi Sankyo introduces Delytact in Japan to treat malignant glioma. com, November 2, 2021.  http://www.pharmabiz.com/NewsDetails.aspx?aid=143694&sid=2 First launch for Daiichi Sankyo’s oncolytic virus Delytact in Japan. Pharmaphorum, November 1, 2021.  https://pharmaphorum.com/news/first-launch-for-daiichi-sankyos-oncolytic-virus-delytact-in-japan/

Life Happens Quickly: Aly’s Story

As we grow older, we learn to understand that life happens quickly. Aly Newel learned just how quickly things could happen when she was screened for, diagnosed with, and received breast cancer treatment, all within 22 days. After losing her mother to breast cancer, Aly devotedly underwent her mammograms as recommended since turning 30 years old. In early 2016, she suddenly realized that she had missed her annual appointment by nearly six months. She quickly made an appointment, not thinking too much about the lapse as everything felt normal.  “My general practitioner told me that the test had detected abnormal cells in my left breast and that she was referring me to a surgeon,” Aly shared. “It wasn’t more than a couple of days before I was with the breast surgeon in absolute shock at how quickly this had happened. With everything that happened with my mom, I was scared.” Aly soon received the biopsy results that quickly filled her with dread as she learned she had breast cancer. Luckily, the ductal carcinoma in-situ was in the early stages and completely treatable.  “I was stunned,” Aly reflected. “How can he have just told me that I have breast cancer, yet it is curable? Honestly, it took me a while to get my head around that.” Before she could fully wrap her head around the news, Aly had a hook wire insertion and lumpectomy.  “These operations sound really scary, but they aren’t at all,” Aly said. “The surgeon came to see me after the operation and told me that everything had gone really well and that the cancer was gone.” Aly felt amazing – pain-free and thrilled to be rid of the nasty disease. She had zero pain and only a little scar on her left breast for which to remember the whirlwind experience. With just a single dose of radiotherapy, she closed this scary yet short chapter.  “I would like to share my story because as a mother of two daughters, I feel that it’s really important to promote early detection by encouraging women to become familiar with the regular feel of their breasts and participate in the screening programs that they are eligible for,” Aly stated. “I also think it’s important for people to realize that being diagnosed with breast cancer doesn’t necessarily have a bad outcome if it’s found early.” Life happens quickly, and sometimes it is easy to forget the small steps that make a big difference – like scheduling regular mammograms. Luckily, the National Foundation for Cancer Research (NFCR) has you covered. Follow NFCR on social media or check out our Cancer-Fighting Lifestyle Tips to keep you and your loved ones safe.  Additional Reads You May Enjoy: Let’s talk about Mammograms with Dr. Alexia Matheson Don’t Delay: Skipping One Mammogram Can Significantly Increase Risk of Death from Breast Cancer Mastectomy and Breast Reconstruction: What Breast Cancer Patients Should Know   Stay connected with the cancer community! Receive NFCR’s monthly e-newsletter and blogs featuring stories of inspiration, support resources, cancer prevention tips, and more. Sign up here.

Don’t Delay: Skipping One Mammogram Can Significantly Increase Risk of Death from Breast Cancer

One mammogram every two years doesn’t sound so bad – but what happens if a woman skips one? A recent study warns that missing just one mammogram before being diagnosed with cancer significantly increases a woman’s probability of dying from the disease.  The Importance of Mammograms Mammograms allow medical professionals to examine an x-ray of the breast tissue and look for any abnormalities or hints of cancer that other methods may not be able to detect. Having regularly scheduled mammograms presents an opportunity for early diagnosis, which significantly increases the ability to administer successful treatment. As signs and symptoms are often difficult to observe at early stages, mammograms have been the gold standard used for cancer detection and may reduce mortality by up to 40%. Because of this, the United States Preventative Services Task Force recommends that women aged 50-74 undergo a mammography every two years. Alarming Study Results In this ground-breaking study, a research team led by Stephen W. Duffy and Laszlo Tabar analyzed data from nearly 550,000 women with access to mammograms between 1992 and 2016. This data was divided into two groups – women who attended the two of the most recent mammograms before being diagnosed with breast cancer and those who did not.  The team discovered that the group who did not attend the two most recent mammograms before their diagnosis were more likely to have died within ten years of being diagnosed. The significant findings showed that 50% more of these group members had died than those who attended both most recent appointments. Overall, women who attended only one of the two breast cancer screenings had 29% higher mortality than those who attended both. While the research team anticipated a higher mortality rate among women who missed even one mammogram before their diagnosis, the disparity was astounding. As researchers unveil more evidence to highlight the importance of mammograms, however, medical professionals continue to identify a decrease in the number of women who undertake regular screenings. Tragically, the COVID-19 pandemic has also caused a significant decline in the number of women attending their regular mammograms.  What Next? Duffy, Laszlo, and their team hope their recent findings will inspire women to keep up-to-date with their mammogram appointments and plan to continue further prognostic research into the mechanisms of this effect. The team will explore to what extent regular attendance improves the prognosis of interval cancers and screen-detected cancers.  While the world eagerly awaits the following report, women must continue adhering to the current mammogram recommendations. Those with questions regarding their personal situation and recommendations should speak to their general practitioner.  For more information regarding breast cancer, please visit NFCR’s breast cancer page.  Note: The third Friday in October we recognize National Mammography Day. This year it will be celebrated on October 15, 2021. Please take this opportunity to schedule your mammogram or share important information with loved ones. Additional Reads You May Enjoy: Let’s talk about Mammograms with Dr. Alexia Matheson National Mammography Day 5 Ways You Can Show Support for Breast Cancer Patients Stay connected with the cancer community! Receive NFCR’s monthly e-newsletter and blogs featuring stories of inspiration, support resources, cancer prevention tips, and more. Sign up here.