Pancreatic Cancer Review
Pancreatic cancer is more prevalent in North America and Europe, and in developed countries overall. It is the 4th leading cause of cancer in the United States and the 5th in United Kingdom. Although the incidence of pancreatic cancer is very low in Africa, it is 1.5 times more prevalent in Black Americans. Although the combined death rate for all cancers has declined in the past 10 years, the death rate for pancreatic cancer has increased by 0.4% each year. Even after the conventional chemotherapy, radiation and surgery, cancer recurrence is high; resulting in a 5-year survival rate of only 1-5%. Two of the main reasons for the high recurrence are the development of therapeutic resistance after repeated treatment sessions and the incomplete killing of tumors due to poor tumor selectivity and cytotoxic efficiency of conventional therapies. Furthermore, in many cancers, therapeutic resistance has been found to be associated with mutations of the KRAS gene, which are present in 95% of pancreatic cancers. The KRas protein is primarily involved in regulating cell division. To date KRas protein has not been druggable. For this reason, chemotherapy is ineffective for patients with KRAS mutation because they come in with pre-existing resistance to therapy. Poor blood vessel network and the dense stroma of the tumor tissue that prevent chemotherapy drugs from reaching the tumor are also reasons why chemotherapy drugs are mostly ineffective in treating pancreatic cancers.
The third reason for the low survival rate is that pancreatic cancer is a very aggressive form of cancer with very poor prognosis. Only 10-15% of pancreatic cancers are caught in early stages and thus can be treated with conventional treatments. Neither an effective diagnostic test of pancreatic cancer nor specific biomarkers to pancreatic cancer exist to detect the existence of the disease in patients.
Because of the complexity of the human body, while many drugs show promise in animal studies, once they are tested in clinical trials, they fail to show any benefit or significant improvement in life expectancy of patients.
The pharmaceutical industry has been concentrating heavily in research and development (R&D) efforts on developing drugs that address unmet therapeutic needs and untargeted biological mechanisms. But, because complex diseases such as cancer are harder to solve, the risk of failure in this industry is the highest.
Approximately 1 in 50 promising cancer drug candidates make it to market. FDA approval rate of cancer drug candidates is 9%. Most of these drug in the 9% group fail in phase I of clinical trials.
Despite these discouraging numbers, there have been advances in the drug development arena resulting in a few early and late stage therapies for pancreatic cancer. Gemcitabine and FOLFIRINOX ((5-flourouracil [5-FU]/leucovorin/irinotecan/oxaliplatin) are chemotherapy drugs used as the first-line of treatment and monotherapy for early-stage resectable pancreatic cancer patients. FOLFIRINOX is highly toxic and only used in patients that can tolerate the side effects. Combination therapy of Gemcitabine with other chemotherapy drugs (e.g. Gemcitabine/FOLFIRINOX or Gemcitabine/Abraxane) are used as first and second-line of treatment for metastatic or pancreatic tumors that cannot be surgically removed (unresectable). Specifically, Abraxane (nab-paclitaxel) was approved in the US and the Europe in 2013 and 2014 respectively as first line treatment of metastatic pancreatic cancer in combination with Gemcitabine. While the sales of Abraxane have been high since its approval, the Abraxane/Gemcitabine combination therapy only extends survival of patients for 2 months compared to Gemcitabine alone, which extends survival to 5 months.
However, there has not been any other early-stage drug for pancreatic cancer since Gemcitabine’s approval for clinical use in 1995 (FOLFIRINOX was approved for medical use in 1962). The late-stage pipeline for pancreatic cancer consists of only six agents that are in Phase III of clinical trials. The pipeline for early-stage pancreatic cancer is very strong and consists of many drug candidates.
While there are many drugs currently in the pipeline, the rate of new FDA approved and effective therapies for pancreatic cancer has been extremely slow.
Therefore, there is still an unmet need to develop drugs across all the patient segments in pancreatic cancer, especially at the metastatic and unresectable settings, that can extend the survival of patients beyond a year after treatment. The lack of late-stage drug candidates also adds to the urgent need of more efficient drugs. Because of this unmet need, the global pancreatic cancer drug market is increasing rapidly, with sales expected to rise to $1.63 billion in the U.S. and Europe combined by the end of 2017.
Key opinion leaders believe that without predictive biomarker-driven target therapies that can home to pancreatic cancer cells only and selectively kill them with great efficacy, the unmet need will remain despite the extensive growth in the market. Key opinion leaders predict that while there are many drugs in the pipeline, unless they can demonstrate a significant increase in survival time (e.g. beyond a year) of metastatic and unresectable pancreatic cancer patients, these drugs will meet the common fate in clinical trials as many drugs that have come before them.
While more effective treatments for pancreatic cancer are being developed, limiting the consumption of processed meat, maintaining a healthy weight, avoiding excess drinking, and especially avoiding smoking, and having regular doctor visits if your family has a history of pancreatic cancer, are measures recommended by the American Cancer Society that can help reduce the risk of developing hard to treat pancreatic cancers.
Keywords: Pancreatic Cancer, Anti-Cancer Drug Market, Oncogenic Pharmaceutical Industry, Drug Development, AWIS STEM-to-Market
Sources: 1. American Cancer Society, Cancer Facts & Figures 2014. 2. Morris, JPt, SC. Wang and M. Hebrok. “KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma.” Nat Rev Cancer 10 (2010): 683–695. 3. “Pancreatic Cancer Drugs Fail”, http://www.fredhutch.org/…/20…/05/pancreatic-drugs-fail.html 4. Pancreatic Cancer - Opportunity Analysis and Forecasts to 2017 report by GlobalData 5. “What's new in pancreatic cancer research and treatment?”,http://www.cancer.org/…/deta…/pancreatic-cancer-new-research