Dr. Hani Goodarzi on AACR NextGen Grants for Transformative Cancer Research
What has inspired you to focus on metastasis, especially in colorectal cancer?
Metastasis is ultimately the main cause of death in most cancers. It involves a complex multistep process that requires cancer cells to survive a perilous journey to other organs in the body and re-establish new tumors. Our lab is broadly interested in molecular and cellular processes that cancer cells leverage to effectively metastasize. At the same time, we seek to understand the molecular basis of tropism, i.e. the reason why specific cancers metastasize to some organs but not the others. Our interest in colorectal cancer metastasis to liver was initially rooted in our goal to compare its underlying mechanisms to those we had previously identified in breast cancer metastasis to the lungs. However, not surprisingly, we quickly realized that liver metastasis is a highly complex phenotype in its own right, and its underlying regulatory mechanisms remain largely underexplored.
What has been the impact of your NextGen grant on your career, and what does it mean, for you, to receive this grant?
For my lab, the AACR-Takeda Oncology NextGen Grant for Transformative Cancer Research grant was extremely timely. For a long while, it was the sole funding source that was supporting our expansion from breast cancer metastasis to colon cancer progression. Through this grant, we developed new tools and models, and formed collaborations with clinicians and scientists that are on-going to this day. At a time that NCI funding has been at a historical low, this support was a crucial pillar on which our lab was built on.
What do you consider the most important scientific advance(s) made, at least in part, because of your NextGen grant?
We recently published a paper describing a previously unknown pathway that suppresses metastatic progression in colon cancer. In addition to providing new insights into the biology of metastasis, through this study we developed new computational and experimental tools that will greatly facilitate our future research as well. More importantly, this study taught us something new about gene regulation in the cells and how cancer cells come up with unique strategies to co-opt or counteract these regulatory programs.
How has your grant allowed you to pursue research that would not have been otherwise possible?
As I mentioned earlier, without AACR support, it is unlikely that my lab would have ventured into studying metastasis in cancers other than breast as early as we did. More importantly, through this study, we formed collaborations that have since expanded to new exciting areas and I look forward to seeing what comes out of these efforts.
If applicable, how has your NextGen grant contributed to your ability to acquire additional research funding, including recently, through a 2020 AACR-MPM grant?
The AACR NextGen grant allowed us to take on a more pan-cancer approach to metastasis. And while the work funded by this mechanism hasn’t been ‘directly’ funded through other mechanisms, it has nevertheless helped us expand our horizons, which in turn has allowed us to attract funding at this critical juncture in our effort to further build on our foundational work over the first few years of the lab.
Is there another scientist in the field whose work excites you or inspires your research and would you like to share how?
There is no shortage of scientists, in cancer research, systems biology, and bioinformatics, who inspire and excite us on a daily basis (including many of my past and present mentors). However, I would be remiss if I don’t mention Dr. Zena Werb, who unfortunately passed away recently. Dr. Werb was truly visionary and a fantastic mentor. I walked out of every meeting with her with a fresh perspective on different aspects of our research, and a renewed sense of urgency. I feel her absence as a mentor, and I am confident that a number of other junior faculty and postdocs share this loss.
In what ways, if any, has the COVID-19 pandemic impacted your research?
Last year was a tough year… a combination of shutdowns and reduced capacity severely impacted our ability to maintain our momentum and productivity. As a part-dry lab, we were not as negatively affected as some of our other colleagues; but it has nevertheless been a brutal year. But I also acknowledge that as scientists, we were privileged to be part of institutions that has taken some steps to protect the scientific enterprise. But as folks are becoming vaccinated, we should be aware that the impact of this year will be felt for many years to come. Rifts and inequalities have continued to grow, and we need to be vigilant now more than ever to help close these gaps.
Since 1993, the AACR grants program has contributed to the development of new and improved approaches to cancer treatment and cure. What is your vision for the future of metastasis inhibition research?
I believe that historically, metastasis has been an understudied area of cancer research. I think this can be attributed to many challenges, including but not limited to the lack of in vitro and ex vivo models of metastasis that would faithfully capture this process. In the absence of scalable in vitro models, we have to rely on mouse models of metastasis that are expensive, low throughput, and labor-intensive. Furthermore, due to low rates of incidence and long remissions, metastasis-free survival as a clinical endpoint is difficult to achieve. Nevertheless, I believe cancer mortality cannot be drastically shifted without a broader emphasis on understanding metastatic progression. In my view, metastasis is a disease in its own right, with mechanisms that are distinct from those involved in primary tumor formation. I believe that advances in computational and experimental technologies will allow us to better understand and hopefully counteract this process.