Susanna’s Cool Cancer Research Finds: March 2024
Every week, Dr. Susanna Greer, the V Foundation's Chief Scientific Officer, shares her cool cancer research finds on LinkedIn. Read more below to see highlights from March 2024’s top finds!
From March 22, 2024
An incredible new tool for our anti-cancer toolkit…
This week’s Cool Cancer Find comes from the V Foundation grantee Dr. Francisco J. Sánchez-Rivera and colleagues at MIT Koch Institute for Integrative Cancer Research.
This paper is incredible-it’s impact will not be realized for years to come, as we will see the application of the tool the lab has developed for decades.
The Sanchez-Rivera lab is focused on developing tools to understand the genetic changes that happen during cancer. These alterations are critical to how aggressive a cancer will be, or not be, like different ingredients in a recipe. Just like how changing the amount of salt in a dish can completely change its taste, different alterations can dramatically affect how cancer progresses or responds to treatment.
What is so incredible about what the Sanchez-Rivera lab did? Well, let me share:
Imagine you have a massive puzzle, and each piece represents a different genetic change that could cause cancer. Researchers have been trying to figure out FOR DECADES how each piece fits together and what it does. We’ve had some amazing tools, you may have heard of CRISPR, to help, but those tools aren’t perfect. It’s like trying to use a slightly broken hammer to build a house – it kind of works, but it’s not great.
Here, Dr. Sanchez-Rivera and team have built a much BETTER tool…the official name is “prime editing sensor.” It’s like upgrading from that broken hammer to a shiny new power tool. With this new tool, we can not only find the right puzzle pieces faster, but we also see how each piece fits more clearly. Plus, the researchers generated a software to allow them to share this tool with other scientists, making it easier for everyone to join in the puzzle-solving.
Before handing the tool off, they tried it on a really important piece of the puzzle called the TP53 gene, which is like a superstar gene in cancer research. What they found was surprising – some pieces of the puzzle were way more important than they thought, especially pieces related to how the TP53 gene works in cancer.
They also discovered that the way scientists have been studying these pieces before may have been a bit off. It’s like we were trying to understand a painting by only looking at it from far away, missing some of the important details. Now, with this new tool, we can look at the painting up close and see everything clearly. And honestly, that’s how research works. We make hypotheses based on the best tools we have on hand now. As our tools get better and better, so do our hypotheses. And so do our results.
This study is like making a breakthrough in solving a complicated puzzle: It will help us understand cancer better, which will lead to new and more precise treatments.
Read more about the Francisco Sanchez-Rivera lab here Francisco J. Sánchez-Rivera – MIT Department of Biology and find their paper at High-throughput evaluation of genetic variants with prime editing sensor libraries | Nature Biotechnology
From February 22, 2024
A Beacon of Hope for the 300K individuals diagnosed with breast cancer annually.
In a groundbreaking initiative led by the V Foundation grantees Dr. Vered Stearns and Dr. Roisin Connolly, at The Johns Hopkins University School of Medicine, researchers have unveiled a game-changing treatment for advanced HER2-negative breast cancer. The study introduces a potent trio of drugs, signaling a new era of hope for patients facing this challenging form of cancer.
The treatment trifecta comprises a histone deacetylase (HDAC) inhibitor, acting as a decisive barrier to halt cancer cell division, accompanied by two of my favorite superheroes in the form of immunotherapies known as checkpoint inhibitors. These immunotherapies unleash the body’s immune system to wage a powerful battle against cancer.
For 24 women with HER2-negative metastatic breast cancer, the results were nothing short of remarkable. A 25% overall response rate was achieved, translating to a quarter of the women experiencing either complete destruction or significant reduction of their cancer. This breakthrough is particularly significant for those grappling with triple-negative breast cancer, a subtype with limited treatment options.
Crucially, the treatment proved not only effective but also safe, with none of the patients needing to discontinue due to adverse effects. The six-month progression-free survival rate of 50% adds a positive note, indicating that, for half of the participants, their disease did not worsen during this crucial period.
This study builds on the transformative impact of immune checkpoint inhibitors (ICIs) in cancer treatment. While ICIs have revolutionized outcomes for some patients, breast cancers, especially the HER2-negative variety, have proven resilient. The integration of the HDAC inhibitor with dual immune checkpoint inhibitors marks a promising turn in the tide.
The findings from Dr. Stearns’ lab and colleagues emphasize the urgency of further exploration, delving into how this treatment reshapes the spaces around tumors, known as the tumor microenvironment, and identifying potential biomarkers for immunotherapy response. This collaborative effort, bridging cutting-edge laboratory research with real-world clinical trials, propels us toward a future where advanced breast cancer may be met with newfound resilience and effective treatment strategies.
This study represents a beacon of hope for the 300,000 individuals diagnosed with breast cancer in the United States annually. It serves as a testament to the tireless pursuit of my HEROS: cancer researchers and cancer patients working together towards innovative solutions that could transform the landscape of cancer care, offering renewed optimism and tangible progress for those in the fight against this formidable disease.
Read the press release here: https://www.hopkinsmedicine.org/news/newsroom/news-releases/2024/02/novel-drug-combination-shows-promise-for-advanced-her2-negative-breast-cancer and find out more about the Dr. Stearns lab at https://vivo.weill.cornell.edu/display/cwid-ves4007
From March 8, 2024
Bladder cancer meets its match.
Bladder cancer is this focus of this week’s Cool Cancer Research Find with an incredible publication from the V Foundation grantee Dr. Pavlos Msaouel, MD, PhD and team out of MD Anderson Cancer Center. Dr. Msaouel’s research focuses on a subset of bladder cancer patients whose tumors lack the gene SMARCB1. To better understand the impact of this study, think about our body as a highly organized city, and within it, the bladder as a crucial hub. Like any city, issues can arise, and a significant one is bladder cancer. Fortunately, our body has a defense mechanism: the superhero team known as SMARCB1.
In this publication, Dr. Msaouel demonstrates that SMARCB1 is like a captain of our superhero squad, responsible for maintaining order and preventing disruptions, especially when it comes to the bladder. The Msaouel lab uncovered that when SMARCB1 isn’t functioning correctly, it’s akin to a superhero team taking a break, allowing bladder cancer to grow unchecked and spread.
In the realm of molecular biology, SMARCB1 is involved in a process called chromatin remodeling. Think of chromatin as a set of instructions that guide how our cells function. SMARCB1, by being a part of this chromatin remodeling team, ensures that these instructions are followed correctly, playing a critical role in preventing the development and spread of cancer.
Dr. Msaouel went a step further and explored a potential solution – with a drug called TTI-101. In the molecular superhero world, TTI-101 acts as a power-up for the SMARCB1 team. It’s a specialized tool that helps to strengthen the superheros, allowing them to better regulate the chromatin instructions. This, in turn, reduces the harmful effects of bladder cancer and slows down its growth.
AND, in another a win for investing in early career researchers: TTI-101, our superhero, is a drug designed by ANOTHER the V Foundation grantee, Dr. David J. Tweardy MD also at MD Anderson Cancer Center. Cheers to scientific collaborations resulting in patient impact! TTI-101 inhibit pathways which, when overactive, contribute to the aggressive behavior of bladder cancer cells. So, TTI-101 is like a precision tool, targeting molecular mechanisms associated with cancer growth.
Why do I love this paper? With additional testing, TTI-101 could serve as a valuable therapeutic strategy, especially in cases where our superhero team, SMARCB1, needs extra support to counteract the disruptive effects of bladder cancer. It’s like providing a targeted solution to restore balance and protect our “city” from the harmful impacts of bladder cancer.
It’s Friday night friends, welcome to the weekend! Start yours by reading Dr. Msaouel’s paper here: The IL6/JAK/STAT3 signaling axis is a therapeutic vulnerability in SMARCB1-deficient bladder cancer | Nature Communications and follow the Msaouel lab at faculty.mdanderson.org/profiles/pavlos_msaouel.html.
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