WASHINGTON—This year, almost 300,000 Americans will be diagnosed with gastrointestinal cancers, and nearly 150,000 Americans are expected to die of GI cancers. But despite that high incidence, research on GI cancers remains underfunded. That was the consensus of speakers here at a symposium on the state of GI cancers, sponsored by the Ruesch Center for the Cure of Gastrointestinal Cancers at Georgetown University's Lombardi Comprehensive Cancer Center.
“We are, as we say, in last place” when it comes to a dedicated research funding stream, said John L. Marshall, MD, Director of the Ruesch Center. “This is a major public health problem, and yet we are in last place.” He decided to hold the symposium, he said, “because this is such a critical area.”
According to statistics presented at the symposium, in the United States colorectal cancer is the second leading cause of cancer death; stomach cancer will be diagnosed in more than 22,000 Americans in 2014; pancreatic cancer is the fourth leading cause of cancer death, and has a low survival rate; and liver cancer and intrahepatic bile duct cancer combined is the seventh leading cause of cancer death.
Asked by OT what he hoped the symposium might accomplish, Marshall said he hoped to raise awareness about the magnitude of the problem of GI cancers; draw attention to the need for public/private partnerships (including collaborations with patient advocacy groups) to advance scientific knowledge on GI cancers; and bring up-to-date U.S. therapies to patients in the rest of the world (stomach cancer is the second leading cause of cancer mortality worldwide).
Currently there are about 800 medicines and vaccines in development to treat cancer and some 200 in development to treat patients with GI cancers, said John J. Castellani, President and CEO of the Pharmaceutical Research and Manufacturers of America (PhRMA). “GI cancers are one of the great priorities that we have.”
He said that realistically, the majority of medicines in development will fail—“but some will be spectacularly successful.”
GI Cancer Medicines in Development
According to PhRMA data, there are currently 46 medicines in development to treat colorectal cancers. One particularly promising therapy is a humanized monoclonal antibody that targets the cell surface protein endosialin, a protein expressed on cells that are part of the tumor blood vessel structure. In preclinical studies, researchers have found that blocking endosialin's function inhibits the growth of cancerous tumors and metastases.
There are 37 medicines in development for liver cancer, according to PhRMA; these include a small molecule kinase inhibitor designed to selectively block transforming growth factor-beta (TGF-beta) signaling. Overexpression of TGF-beta in cells may boost tumor growth and intensify the metastatic process.
PhRMA data also show that there are currently 24 medicines in development to treat stomach cancer; one of these is a monoclonal antibody being tested for stomach cancer with high mesenchymal-epithelial transition factor (MET) expression that is designed to inhibit hepatocyte growth factor (HGF)/scatter factor from binding to the c-MET receptor. The HGF-cMET signaling pathway is believed to play a role in tumor growth and metastases in many cancers, including stomach cancer.
As for pancreatic cancer, there are 39 therapies currently in development. One of these takes advantage of tumor hypoxia, which is associated with tumor progression, metastases, and resistance to chemotherapy and radiation. This investigational therapy is activated when it reaches the hypoxic region of the pancreatic tumor environment, where it eventually kills tumor cells in its vicinity.
‘Epicenter of Research’
“We see that the U.S. is the epicenter of research,” said Castellani, adding that PhRMA companies regularly partner with academic institutions, the hospital system, and patient groups—“This is progress based on each patient incrementally.”
Asked how he counters critics who charge that many cancer treatments cost too much and add only a few months of survival, Castellani answered that medicine accounts for only about one percent of the cost of cancer care. As for months of survival, he said, “The nature of the science of the discovery process is hard. The discovery process is not a stop-start process; it's a continuum. I dare anyone to say how long each patient will live when they start on a drug.”
Castellani noted that the fees pharmaceutical companies pay to the US Food and Drug Administration through the Prescription Drug User Fee Act (PDUFA) are invested in improving and speeding the regulatory process at the agency. “We believe it's incumbent on us to make that process quicker and better,” he said.
Marshall added that from his clinical experience he has found that some cancer patients are outliers, and live well beyond an average survival time when they start on a drug—“We can learn from outliers,” he said.
Centralized Banking System for Tumor Samples
Allen Melemed, MD, Distinguished Medical Fellow at Eli Lilly & Company, decried the fact that so few adults participate in cancer clinical trials, as opposed to the situation for children with cancer. He said that in addition to enrolling more adults on clinical trials, it is vitally important to have a centralized banking system to gain access to tumor samples.
“We need to have a better way to identify those genes earlier,” he said of mutations. “Stage IV is very hard to cure; we need to get patients at earlier stages.”
Speakers at the symposium emphasized that Congress plays a key role in keeping funding for cancer research, including funding for GI cancers, strong. Funding for biomedical research “is as close to a non-partisan issue as there is,” said David Pugach, Director of Federal Relations for the American Cancer Society Cancer Action Network (ACS-CAN). But, he noted, cuts to the budget of the National Institutes of Health have been very damaging.
Cancer research is an ecosystem; what we're seeing is a real disruption of the ecosystem,” he said.
Wade Ackerman, Senior Counsel of the U.S. Senate Committee on Health, Education, Labor & Pensions, noted that Senator Tom Harkin (D-Iowa), a longtime advocate of funding for biomedical research, is retiring and did not run in the recent November election.
“It's hard to overstate his support for NIH funding,” said Ackerman of Harkin's long commitment to boosting the NIH budget. But, said Ackerman, “I see the future being just like the past; we roll up our sleeves on an issue and get it done. With a new Congress comes new opportunity... I do think advocates for biomedical research will emerge in the new Congress. People are using the ebola crisis as a way of advocating for the public health infrastructure.”
In an era of flat funding for biomedical research, “we are open to looking at places where we can reallocate monies in the federal budget to NIH,” he added.
Paul Edattel, who is on the professional staff of the U.S. House of Representatives Committee on Energy & Commerce, said, “We hope money will free up for NIH... You need bipartisanship to get things done.”
He noted that Rep. Fred Upton (R-Mich.), Chairman of the House Committee on Energy & Commerce, is a champion of NIH. Upton, who recently won reelection, launched the 21st Century Cures Initiative earlier this year with co-convener Rep. Diana DeGette (D-Colo.). That initiative seeks to modernize clinical trials; facilitate data collection and data sharing; provide incentives to pharmaceutical companies to pursue drug and device research for unmet needs; incorporate the patient perspective into the research and regulatory process; develop and support young emerging scientists; and develop a stable funding stream for U.S. biomedical research.
Voice of the Patient
The House committee has sought ideas and listened to stakeholders all across the United States, said Edattel. One message the committee has heard again and again from patient groups is that their voice, the voice of the patient, needs to be heard more consistently in the regulatory-approval process for drugs and devices, he noted.
Patient groups were on the agenda and well represented at the GI cancers symposium. For example, Michael Sapienza, President of the Chris4Life Colon Cancer Foundation, whose mother died of colon cancer and was a patient of Marshall's, described being motivated to found an organization to honor her memory, help other colon cancer patients, and help to find a cure.
Beth Lambert, Board Chairman of No Stomach for Cancer, described what it is like to have a rare mutation that causes stomach cancer and runs in her family, to lose her brother to stomach cancer, and to opt to have a gastrectomy herself. “It's very intimidating to get that news,” said Lambert. “We were lucky with our mutation that there was a solution.”
Sharon Brigner, RN, Deputy Vice President of PhRMA, also described having a gastrectomy due to a mutation. “My focus has radically changed,” she said. “When I was sitting in that hospital bed, I realized I needed to be working for innovative medicines. Hopefully this ends with me and my family.”
Elizabeth Hoffler, Senior Director of Policy and Advocacy for the Prevent Cancer Foundation, whose mother has a brain tumor, emphasized the power of a cancer patient's story in advocating for cancer research. “The most important advocate is someone's personal story,” she said.
Lambert agreed: “You have to tell your story, and that's the best way to be an advocate.”