When cancer patients are initially diagnosed, they eagerly wonder if it’s curable. That’s because pharmacists and doctors are engaging in the development of novel treatment regimens that are expected to be more effective than traditional chemotherapies, and have fewer side effects. Indeed, they’re finding that therapeutic combinations have the potential to be more effective in slowing or even blocking cancer growth.
Biologic agents act against oncogenic proteins or enzymes in tumor cells that drive cancer development. However, considering complex signaling networks, including these proteins, interact through crosstalk and feedback loops to form drug resistance , clinical physicians would envision several trial designs to achieve the optimal drug combination.
“Cell signals operate in pathways, or networks, similar to interstate highways. When the interstate is clear, traffic runs smoothly. But an accident at one part, or a closed exit ramp, can lead to massive traffic snarls. That’s what happens in cancer, where an error in any signal along the pathway can bring the entire growth-regulating system to a halt.” explains Lebwohl, senior vice president and global head of Oncology Clinical Development at Novartis.
Biomarkers and therapeutic combination
Nearly all pharmaceutical companies are investigating oncogenic proteins, or biomarkers, which initiate the development of potential drugs. For instance, currently most of Roche’s anti-cancer drug candidates in clinical development are being developed with targeted biomarkers, by which doctors can distinguish the certain patients with potential pharmaceutical benefit.
Biomarker studies can help to understand disease biology and to identify patient subgroups in favour of genotyping. Moreover, biomarkers can help to understand the outcome of therapeutic combination and how to rationally design therapeutic combination. Finally, another goal of biomarker research is to understand the development of resistance against cancer therapies and overcome this issue.
A successful therapeutic Combination against cancer
A new study, published in the Lancet oncology, firstly demonstrate chemotherapy and a targeted therapy in combination work better than chemotherapy alone in treating lung cancer patients with KRAS mutation.
The 87 patients who participated in the phase II trial had advanced, KRAS-mutant NSCLC that had failed initial chemotherapy. They were randomly assigned to receive either selumetinib and the chemotherapy agent docetaxel or docetaxel alone. As investigators found, patients receiving selumetinib lived a median of 5.3 months before their cancer began to worsen, compared to 2.1 months for those receiving chemotherapy alone.
“Our findings suggest that selumetinib and docetaxel work synergistically – each enhancing the effect of the other,” says Dr. Pasi A. Jänne, HMS associate professor of medicine at Dana-Farber Cancer Institute. “This opens the possibility that there may finally be a therapeutic strategy using a targeted therapy which could be clinically effective in this population of KRAS-mutant lung cancer patients.”
References:
1. Development of therapeutic combinations targeting major cancer signaling pathways. J Clin Oncol. 2013;31(12):1592-605.
2. Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study. Lancet Oncol. 2013;14(1):38-47.