Unfortunately, the survival rate for pancreatic cancer patients has not improved substantially in almost four decades. In fact, by the time most patients are diagnosed, it’s likely to be considered incurable, and most pass away within 12 months.
One main cause of the poor outcome is its peculiar way of dissemination. Traditionally, cancer researchers have focused on studying dissemination by three main ways: direct invasion, lymphatic spread, and hematogenic spread. However, today we know that there is a fourth way of cancer spread that is frequently disregarded, dissemination along nerves.
Invasion of nerves by cancer cells occurs in almost all pancreatic cancers as well as in prostate, gastrointestinal, and head and neck cancers. This leads to poor quality of life due to pain and disability, and subsequently to the unresectability of the tumor and worse survival chances. For years, it was thought that tumors spread along nerves since it’s the path of least resistance, as such invasion cannot be halted by anti-cancer drugs. Due to a recent finding that changed this understanding, scientists now try to find new drugs that will postpone tumor dissemination along the nerve in a contest to save lives.
The micro environment within the tumor is complex and many factors are involved in the cancer dissemination process. These factors include immune cells, connective tissue, nerves and their coverings. A major challenge in studying the mechanisms that drive cancer cells to invade nerves is modeling this phenomenon. In this regard, the laboratory for applied cancer research at the Rambam Health Care Campus, of the Technion — Israel Institute of Technology, in Haifa, Israel, is one of the leading labs in the field of cancerous neural invasion modeling.
The research conducted at our lab showed the role of immune cells, namely, macrophages, in mediating the invasion of cancer cells into nerves as early as the precancerous lesion is evident. Both in cell cultures and animals, the blockage of macrophages resulted in lesser invasion and enhanced survival.
These findings were achieved using microscopic assays that allow imaging of cell locomotion along axons; tumor specimens excised from patients, and novel animal models that mimic the spectrum of the human disease. The demonstration that specific interactions between cancer cells and nerves can induce invasion is encouraging; especially with the recent emergence of drugs that modify the way our body responds to the development of cancer.
Understanding the complexity of the neural invasion process and the mechanisms that drive cancer cells to invade nerves is the first step in the development of therapeutic means to inhibit it. For inoperable primary tumors and for patients with a high likelihood of nerve invasion, such targeted treatment is also likely to decrease neuropathic pain, prolong survival and improve quality of life.