Alan P. Venook, MD, is a nationally renowned gastrointestinal (GI) oncologist at the University of California, San Francisco (UCSF), where he serves as the Madden Family Distinguished Professor of Medical Oncology and Translational Research and the Shorenstein Associate Director for Program Development at the Helen Diller Family Comprehensive Cancer Center. Over his decades-long career, he has led pivotal clinical trials, including the CALGB/SWOG 80405 study, which advanced the observation of differences in colorectal cancer prognosis based on tumor location. Dr. Venook has also played key roles in national oncology leadership, chairing the GI Committee of the Alliance for Clinical Trials in Oncology (initially the Cancer and Leukemia Group B) and serving as the first chairperson of the National Cancer Institute’s Hepatobiliary Task Force.
In this exclusive interview with GI Oncology Now, Dr. Venook reflects on how his leadership roles have shaped his collaborative approach to cancer research and treatment. He emphasizes the importance of mentorship and team science, highlighting his efforts in developing the GI oncology program at UCSF and helping to shape the survivorship and integrative oncology programs at UCSF. Despite personal health challenges, including a diagnosis of Parkinson’s disease, he has remained actively engaged in advancing the field. Looking ahead, Dr. Venook identifies the rise in early-onset colorectal cancer and the need to enhance immunotherapy effectiveness as critical areas for future research. He continues to contribute to the field through his role as vice chair of the National Comprehensive Cancer Network (NCCN) guidelines panel for colon/rectal /anal /small bowel appendix cancers, demonstrating his enduring commitment to improving patient care and outcomes.
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Can you walk me through how you came to specialize in gastrointestinal oncology, particularly in colorectal and liver cancers? What motivated you to focus on this field, and were there any mentors or pivotal experiences that influenced that decision?
Dr. Venook: When I started my career, the field was quite open, and I received advice from one of my mentors at the time. He was not a GI cancer specialist—he was a hematologist and the head of our fellowship program—but he advised me to look for an area with opportunities, somewhere there was room to grow. Of course, there were many more such opportunities back then than there are now. He told me, “Just become an expert in something.” So I thought, “Well, okay, what are the options?”
This was around the era when AIDS was just beginning to be understood. There were many AIDS-related malignancies, such as AIDS-related lymphoma, and a lot of people were already interested in that space. But I looked around my institution, UCSF, where I was doing my fellowship.
I decided to stay at UCSF after my fellowship and was brought onto the faculty. I was probably the fifth or sixth faculty member hired at the time. Now, we have around one hundred. In those early days, all of us covered everything, but after about five years, we began to specialize. I would say I was among the first to start a focused GI oncology program at UCSF, probably around 1991 or 1992.
At that point, I had just joined the faculty and was looking for areas of strength at the institution. We had a new liver transplant program that was very highly regarded, and there was a surgeon and an interventional radiologist who were both deeply interested in liver tumors. That struck me as an opportunity. I essentially aligned myself with them and took the lead from their interests and efforts.
The interventional radiologist, in particular, was working in what was then a relatively new field. He had nerves of steel—he would attempt almost anything at any time—and he was constantly pushing for innovation. That kind of energy was very inspiring. That is how I found myself in GI oncology. It was a field in need of attention, there were enthusiastic collaborators, and the environment made it a great system for me to step into.
Your research has emphasized regional treatments for liver tumors. Can you describe some of the key advancements you contributed to in this area and how they have affected patient outcomes?
Dr. Venook: That is actually where I began. Back in the 1990s, when we were treating colon cancer, we had almost no effective therapies. The only drug we really had was 5-FU [5-fluorauracil]. At UCSF, there was strong interest in regional treatments—either through interventional radiologists, which was quite innovative at the time, or by implanting pumps to deliver chemotherapy directly to the liver—simply because we lacked better systemic options.
I became involved in several of those ongoing programs. I learned the techniques and figured out how to do them effectively. Over time, I also realized that there was a limit to how far regional approaches could take us. While I published on the topic, it became increasingly clear to me that we needed systemic treatments in order to make a real impact on survival.
By the mid-to-late 1990s, new drugs started to emerge—taxanes, oxaliplatin, and biologics like bevacizumab (Avastin). I was involved in the early development of several of those agents. At that point, I had already been recognized as one of the few people committed to GI oncology, so when pharmaceutical companies began exploring the potential in colorectal cancer, it was natural for me to be involved.
I was not necessarily the lead investigator, but my group contributed significantly to the early clinical work. For example, we helped with the development of panitumumab and cetuximab. My colleague, Emily Bergsland, presented the first data on Avastin in colon cancer at ASCO [American Society of Clinical Oncology]. We also had a strong clinical genetics program right next door, which created even more opportunities to explore the molecular side of treatment.
Your observations in the CALGB/SWOG 80405 study helped bring attention to the importance of tumor “sidedness” in colon cancer. How has recognizing the biological differences between right- and left-sided colon cancers changed treatment strategies?
Dr. Venook: CALGB/SWOG 80405 was a large, randomized trial in patients with advanced colorectal cancer. The study was designed to compare chemotherapy combined with either cetuximab or bevacizumab (Avastin). When we launched the trial in 2004, we did not yet understand the importance of RAS mutations, so patients were not initially selected based on that biomarker. Over time, we learned that patients with RAS mutations do not benefit from EGFR inhibitors, and we adapted accordingly.
Fast-forward about 10 years, and I presented the results at ASCO in 2013. Interestingly, our findings were quite different from those of a similar European study, FIRE-3. Their data showed a strong benefit with EGFR inhibitors, while ours showed no significant difference in outcomes between the two arms. Yet, both studies reported better-than-expected survival overall.
This discrepancy really puzzled me. I began wondering if there were biological reasons—maybe differences in how the treatments were administered or underlying tumor biology. Around the same time, I was invited to deliver a memorial lecture in honor of my late colleague, Scott Wadler, who had been at Cornell and passed away from a brain tumor. In preparing for the talk, I revisited some of his older work, including a study from the late 1980s or early 1990s on 5-FU. In that paper, I noticed a striking paragraph that noted patients with right-sided colon cancers had a median survival of 10 months, while those with left-sided tumors lived around 15 months.
That really caught my attention. I thought, “That is a huge difference.” So I asked myself, “Do we see the same pattern in our 80405 trial?” But to answer that, we had to go back and manually review data from over 2,500 patient charts because we had not collected tumor sidedness information in the original design.
When we finally analyzed it, my statistician emailed me with multiple exclamation points. I called her and said, “You need to recheck this. Something must be wrong.” She replied, “I already did.” The difference in overall survival between right- and left-sided tumors was about 16 to 18 months. That is enormous.
To this day, we have a fairly good understanding of why that might be. Patients with right-sided tumors derive little to no benefit from EGFR antibodies—even if they are RAS wild-type. It is not just about RAS status; it is also about tumor location.
The biology supports it. The right and left colon actually originate from different parts of the embryonic gut—the right from the midgut and the left from the hindgut. They merge at the transverse colon, but developmentally and molecularly, they are quite distinct. This likely explains why we see such different responses and outcomes.
When I first presented this at ASCO, many people were skeptical. But since then, study after study has confirmed the finding. What surprises me most is that we had not realized it sooner. It seems so obvious in hindsight.
You have held several national leadership positions, including founding Chair of the NCI Hepatobiliary Task Force and Chair of the GI Committee of the Alliance for Clinical Trials in Oncology. How did these roles shape your approach to cancer research and collaboration?
Dr. Venook: It gave me a broader perspective on the field and a deeper appreciation for the power of collaboration. Now, part of it is a bit circular. You are selected for those positions because you have already shown an ability to work well with others. I would like to think that has been a constant in my career: working collaboratively, mentoring others, and helping make decisions. These were incredibly important roles that gave me a fair amount of influence. Around that same time, I was also the GI Section Editor at JCO [Journal of Clinical Oncology] and served as ASCO’s Scientific Program Chair in 2014.
All of those things together really made me feel like I was at the top of my profession—and very busy. You can include this if you wish: I was diagnosed with Parkinson’s disease about five years before that point. So part of my thinking was, “How long will I have to be fully functional?” I did not necessarily seek out every opportunity, but when they came along, I took them—sometimes all at once—because I was not sure I would have another chance. Remarkably, 21 years later, I am still doing reasonably well, but that diagnosis definitely colored how I approached things at the time.
What those leadership roles gave me was visibility into every aspect of GI cancer research. I got to know the field inside and out—and I got to know everyone in it. Hopefully, I set a good example. People knew me as someone who was diligent, honest, and ethical.
One of the other things those roles taught me—particularly in the cooperative group setting—was how hard it is to get things done. It takes time. It takes consensus. While consensus itself is not a problem, sometimes you are dealing with people at the NIH or other agencies who may not have the same level of expertise. That was before the political noise we are seeing now. Unfortunately, it taught me a bit about what does not work—but also about what does. The only way to accomplish anything meaningful is by working together.
During my tenure as GI Chair of the Alliance, I think we did really impactful work. We completed the PROSPECT trial, which was later presented as a plenary at ASCO. We completed 80405. We did five or six meaningful studies that answered real questions. We also launched the whole concept of borderline resectable pancreatic cancer with the Intergroup study led by Dr. Matt Katz.
Again, it all reaffirmed the importance of collaboration—of getting people around you who like working with one another. That philosophy shaped the way I built my own program at UCSF. It is all about working together.
In your role as the Shorenstein Associate Director for Program Development at UCSF’s Helen Diller Family Comprehensive Cancer Center, what initiatives have you led to strengthen the GI oncology program and mentorship culture?
Dr. Venook: I have had a few titles over the years, but I do not want to make too much of it. That said, I have been fortunate to hold two endowed chairs at UCSF that really enabled my work. One is the Shorenstein Chair at the Cancer Center, supported by a very generous and grateful family. The other is the Madden Family Distinguished Professorship in Translational Research. This is endowed by John and Virginia Madden’s Family Trust and is in appreciation for my care of their oldest son, Mike, who was diagnosed with metastatic rectal cancer shortly after John retired and is still living cancer-free almost 15 years later. One of the surprising and more rewarding elements of my career has been the opportunity to interact with, and in the case of the Madden’s, to develop a relationship with “celebrity families.” John Madden was incredibly generous and supported me personally and professionally. He was truly a giant of a man.
In terms of programs I am proud of beyond the GI program, I would say two stand out: survivorship and integrative oncology. We developed one of the first survivorship programs at UCSF, back when it was still a relatively novel idea. Every cancer center has one now, but at the time it was ahead of the curve. The integrative oncology program has also been something I deeply believe in—not because I am a zealot for alternative medicine, but because it is important to give patients some sense of control during treatment. Whether it is diet, nutrition, vitamin D, or other supportive care strategies, it is about empowering patients while they undergo chemo or other therapies.
From the 80405 study alone, we have published around 30 papers—including work on diet and other lifestyle factors that has been a fruitful area of research. I also tried to develop a Chinese herbal medicine program, inspired in part by my long-standing relationship with Fudan Cancer Center in Shanghai, where I have served on their advisory board. Unfortunately, I was not able to get the philanthropic support needed to build that program at UCSF. That was a disappointment, but the integrative oncology program has been a real success.
Honestly though, I think my greatest accomplishment has been mentoring. I have had the privilege of working with incredibly talented young people—many of whom just needed the right environment to thrive. If you find the right fit and then get out of their way, they take off. That has been the most fulfilling part of my work.
When all is said and done, I may be remembered for sidedness in colorectal cancer—which is fine —but what I am really proud of is the group of people I have worked with and helped develop.. We now have 18 GI oncologists—– including people like Emily Bergsland, who is internationally known for her work in neuroendocrine cancer; Andrew Ko, a major figure in pancreatic cancer; Chloe Atreya and Katherine Van Loon in Integrative and Global Oncology and Katie Kelley, who is one of the world’s leading experts in hepatobiliary cancers.
I could add other luminaries whose careers I believe have helped shape, albeit not at UCSF, including Kimmie Ng of the Dana Farber, Aparna Parikh at MGH, and Ghassan Abou-Alfa at Memorial Sloan Kettering. That is the legacy of which I am proudest. When I retire, they are who I leave behind.
I like to think I helped them along the way. But mostly, I just tried to support them, give them space, and let them grow. Some of the people I mentored started as research coordinators—friends of my kids, even—and one is now a practicing GI oncologist in the Bay Area. That is where I made the biggest difference: mentoring talented people, giving them opportunity, and helping build something lasting.