Recent Developments in Pancreatic Cancer

Pancreatic cancer is recognized as one of the most lethal diseases in the world, remaining one of the diagnoses that no doctor wishes to ever have to deliver. Its insidious nature, characterized by few distinguishable symptoms, often prevents early detection, which is crucial for survival. Tackling the challenges represented by pancreatic cancer and improving the outcomes for the people it affects, with nearly half a million diagnoses each year, can bring significant relief to an underserved population. Doing so requires enlisting novel technologies to accelerate detection, as well as innovative treatments that can defeat the disease.

Pancreatic Cancer at a Glance

Pancreatic cancer is a collective term describing a group of cancers that can arise in the pancreas – although over 90% of cases are pancreatic adenocarcinomas. These tumors originate in enzyme-producing cells in the pancreas, and are also the most lethal form of pancreatic cancer. Other types are collectively termed non-adenocarcinomas include neuroendocrine pancreatic tumors, which originate in the hormone-secreting parts of the pancreas – these are associated with slower progression. This article will largely focus on pancreatic adenocarcinomas.

While breast, prostate and lung cancer are projected to remain the most common diagnoses of cancer all the way until 2030, pancreatic cancer is set to be the second leading cause of cancer-related mortality. This is due to its dramatically low survival rate – with 5-year survival at 9% in 2018 (up from 6% in 2014). Incidence of pancreatic cancer is also set to continue growing, further amplifying the burden represented by the disease. 

Finding the Cancer

Early stages of pancreatic cancer – before the tumor invades nearby organs or tissues – rarely come with noticeable symptoms. And when symptoms do occur, they are very difficult to classify as cancer. These include weight loss, abdominal pain, jaundice or diabetes – reports even signify a higher risk of depression prior to diagnosis. Early detection can facilitate surgical resection of the cancer – particularly if the tumor is found before Stage III progression. 

However, curative surgery is incredibly invasive and devastating in itself. If the tumor lies on the head of the pancreas, removal of parts of the stomach, most of the pancreas and the duodenum are performed, with the bowel then rejoined together in a bypass. Even without post-operative complications, quality of life is significantly reduced – patients immediately become diabetic after losing the autonomous enzymatic control afforded by a functioning pancreas. Additionally, the median 5-year survival rate after operation in 2011 was 27 months – still lower than multiple forms of other cancers. Distal pancreatectomy can be offered to patients whose tumor is localized to the pancreatic tail, and can be minimally invasive, although survival rates still hover around 31 months.

Despite the grim comparison between post-operative survival with other cancer survival rates, surgery remains one of the best options to multiply survival rates many times over. New technologies promise to make surgery possible by diagnosing patients sooner – particularly through visual diagnostics powered by Artificial Intelligence (AI). An AI tool developed by researchers from Cedars-Sinai demonstrated the ability of the technology to spot very subtle clues of pancreatic cancer on CT scans years before the occurrence of the disease. The majority of these scans were performed after patients reported abdominal pain in the ER, but the signs of cancer were impossible to find for the human eye. By comparing molecular changes on the surface of the pancreas of patients later diagnosed with cancer against those by people who did not, the model was able to offer significantly accurate predictions. Such early detection can facilitate curative surgery that is often less invasive. 

Novel Treatments

In addition to using AI to accelerate diagnostics, the field of pancreatic cancer is also beginning to see intensive progress in pharmaceutical treatment options – of the kind that is being observed in areas such as lung cancer. Chemotherapy is often used in an attempt to reduce locally advanced cancers to a resectable size. FOLFIRINOX is the standard of care in this regard, though promising results are also being observed for gemcitabine/nab paclitaxel combination therapies – particularly in patients who have not responded to FOLFIRINOX treatment. RenovoRX has demonstrated that its proprietary catheter technology with the combination treatment can deliver results similar to the standard of care, diversifying the arsenal available against pancreatic cancer.

Rintatolimod, marketed as Ampligen by AIM ImmunoTech, has also shown potential to maintain progression-free advanced pancreatic cancer in patients treated with FOLFIRINOX. The therapy is postulated to increase B-cells in circulation and promote control of possible tumor development by enabling the immune system to better modulate the tumor – with a possible increase of over 8 months in survival for patients on rintatolimod maintenance therapy.

Beyond traditional chemotherapies and novel immune-based strategies, the pancreatic space is also seeing innovation in groundbreaking modalities such as oncolytic viruses. VCN-01, developed by VCN Biosciences (later acquired by Synthetic Biologics), has demonstrated multi-pronged functionality in the fight against pancreatic cancer. In an article on Nature’s website, the virus was shown to promote immune system infiltration in the tumor site. The virus-based treatment was also found to disrupt cancer stroma and promote delivery of chemotherapeutic agents in addition to exerting its own antitumor effects. Future research conducted in the field aims to improve the uptake of the virus and reduce the opposition it faces from neutralizing antibodies. A second candidate, VCN-11, has demonstrated improvements in this regard.

It is clear that there is a large space for improvement in the field of pancreatic cancer – from earlier detection to employing novel treatments. Even small increases in survival represent a large fraction of progress, given the terrifyingly lethal profile of the disease. Utilizing cutting edge technology to facilitate earlier detection will prove pivotal in facilitating curative surgeries. Strategies managing the disease through chemotherapy and novel immunotherapies show promise – but further innovation is required to combat the rising incidence of this cancer.

Nick Zoukas, Former Editor, PharmaFEATURES

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