Let's face it: The prospect of fighting cancer is scary regardless of what cancer type you're diagnosed with. However, select cancers are certainly more lethal than others.

Last year, when we examined the 12 most-diagnosed cancer types, we noted certain types of cancers, such as thyroid cancer and melanoma, which, while deadly if caught too late, have a high success rate if caught early and treated. By comparison, other cancer types are difficult to treat in practically all stages, such as lung cancer, which is only the third most-diagnosed cancer but accounts for more deaths in many and women annually than any other type of cancer.

Yet even lung cancer boasts a 17% survival rate after five years according to statistics from the American Cancer Society. Believe it or not, there's an even more lethal type of cancer out there that will be diagnosed in approximately 45,000 people annually, and of which just 6% will be alive five years from now.

This most lethal type of cancer, which is the direct cause of some 38,000 deaths each year, is none other than pancreatic cancer. 

Source: American Cancer Society, data from Bilmoria. 

Understanding your enemy
Although pancreatic cancer can affect endocrine and exocrine glands, exocrine tumors such as pancreatic ductal adenocarcinoma, or PDA, make up the bulk of diagnoses. As the Cancer Research Institute notes, pancreatic cancer is the only cancer type with a five-year survival rate in the single-digits.

Part of that has to do with the fact that early stage pancreatic cancer presents few to no symptoms, causing patients to catch the disease too late, when it's already metastasized to other parts of the body. Even early discovery is no guarantee of success, with complete surgical resection resulting in a relapse in four out of every five cases and only improving five-year survival rates to a range of 18% to 24%. 

The other part of the problem is that not a lot is known about pancreatic cancer even now, despite decades of ongoing research. Unfortunately not all cancer cells behave similarly, and PDA has been particularly difficult to figure out. Factors like smoking, obesity, and getting older definitely increase your risk of developing this disease, but pancreatic cancer cells are also known for their unique biological barrier that they build, making it very difficult for chemotherapy to treat the original tumor.

Meshing the old ...
The current standard of treatments available certainly offer improved quality of life and progression-free survival, but the fact remains that few, if any, of the following FDA-approved drugs is having any meaningful effect on extending overall survival for pancreatic cancer patients.

Source: Novartis.

Perhaps the three best-known pancreatic cancer treatments are Pfizer's Sutent, Novartis' Afinitor, and Eli Lilly's Gemzar, which has been a staple in pancreatic cancer therapy for more than a decade. Both Sutent and Afinitor delivered very similar progression-free survival results in the clinical studies that led to their approval -- 10.2 months and 11 months, respectively -- but neither had a significant impact on overall survival. Folforinox is another potent chemotherapy combination compound given to advanced pancreatic cancer sufferers, but it's often too toxic to be taken for long periods of time.

One recently approved therapy that could hold promise is Celgene's (CELG) Abraxane, which is also approved to treat breast cancer and lung cancer. Abraxane was approved last year in combination with Eli Lilly's Gemzar and helped improve median overall survival to 8.5 months from 6.7 months with just Gemzar alone.

Admittedly, this handful of therapies isn't enough to make a meaningful dent into pancreatic cancer. Instead, researchers are having to think outside the box in an attempt to mesh the old way of thinking with new ways of achieving meaningful survival benefits. The result has been some intriguing new treatment pathways, which could eventually deliver for both patients and investors.

... With the new
There are really four unique ways that researchers and biopharmaceutical companies are tackling the complexity that is pancreatic cancer beyond just traditional medicine. Let's have a quick look at an example of each new method and see what promise the future might hold in treating the most lethal cancer.

Source: Novartis.

Antibody-drug conjugates: ADCs, for short, attach a chemotherapy toxin onto an antibody, allowing that toxin to stay attached until it comes into contract with a very specific protein signature found in the cancer cell at which point it releases and hopefully destroys that cancer cell. The goal of ADCs is to reduce the amount of healthy cell death while delivering a more potent dose of chemotherapy to cancerous cells.

One therapy worth watching here is Immunomedics' (IMMU) IMMU-132, which demonstrated impressive disease control rate in a phase 1 study of solid tumors. Pancreatic cancer was among one of those solid tumors being studied. IMMU-132 is currently in mid-stage studies, and I suspect Immunomedics won't have any trouble finding a partner or funding if this phase 2 study is a success. 

Immunotherapy agents: Perhaps the hottest trend emerging from the fight against cancer is that of reprogramming the body's immune system to recognize cancer cells and to fight back. Under normal circumstances, cancer goes undetected by the immune system, allowing it the ability to grow unabated. The goal of immunotherapy drugs and vaccines is retrain the body's immune system to think otherwise.

A name worth watching here is NewLink Genetics (NLNK), whose HyperAcute immunotherapy platform is geared at teaching a patient's body how to recognize and attack cancer cells. NewLink's lead drug is Algenpantucel-L, which is currently in two late-stage pancreatic cancer trials (one for resectable cancer and for non-resecetable cancer). Algenpantucel-L consists of two pancreatic cancer lines that have been genetically modified to be picked up by the body's immune system. Once injected into the body, it helps the immune system zero in on a patient's pancreatic cancer cells. 

Another extremely intriguing study out of the University of Cambridge's U.K. Cancer Research Institute in late December showed that AMD3100 was effective in breaking down the protective barrier that protects pancreatic cancer cells, allowing the toxin to eliminate nearly all pancreatic cancer cells in models. The drug works with an antibody to ensure that T-cells designed to destroy pancreatic cancer cells don't interact with the CXCL12 protein that protects these cancerous cells, clearing a pathway for the T-cells to directly target pancreatic cancer cells.

Anti-cancer stem cell therapeutics: Instead of fighting cancer cells the traditional way, researchers are instead targeting cancer stem cells, or CSCs, which are believed to have similar characteristics as normal stem cells. Specifically, CSCs are believed to be extremely resistant to chemotherapy and are considered the primary cause of secondary tumors, relapses, and global metastases.

One company targeting the CSCs is OncoMed Pharmaceuticals (OMED), although, like Immunomedics, it's still a bit wet behind the ears. Later this coming week OncoMed will be presenting two studies at the Gastrointestinal Cancers Symposium, including two phase 1b pancreatic trials involving its lead drug demcizumab and OMP-59R5. The data from the demcizumab trial will merely be updated while the OMP-59R5 trials will yield fresh interim results. Given OncoMed's huge partnership with Celgene announced last month, I'd have to suspect that encouraging data is headed our way later this week.

Tumor hypoxia: I only know of one company smart enough to attempt to treat various types of cancer with hypoxia-targeted drugs, and that's Threshold Pharmaceuticals (NASDAQ: THLD). Because cancerous tumors grow in unregulated patterns, there are often cells within tumors that get starved of oxygen-rich blood. While that does slow their ability to divide and form new cells, they often go undetected by most chemotherapy treatments. A tumor-hypoxia drug will seek out this low-level oxygen grouping of cells that's common in cancerous tumors but rare in normal tissue and attack it.

Threshold's lead product is TH-302, which is a DNA alkylator being targeted at a number of therapies, including pancreatic cancer. Currently, Threshold and its collaborative partner Merck KGaA are running a global phase 3 trial, known as Maestro, to assess the effect and safety of TH-302 in combination with Gemzar on advanced-stage but treatment-naive patients. Phase 2b results of this combo demonstrated a 41% reduction of risk for disease progression or death and improved 12-month overall survival to 38% versus 26% in the placebo arm. 

We've certainly got a long way to go, but the future looks promising.