The SENS Research Foundation is currently raising funds for the next step in its cancer research program: building one of the necessary foundations for a universal cancer therapy, one form of treatment that can in principle halt all types of cancer. This requires putting a stop to the lengthening of telomeres in cancer cells, as without that ability cancer tissue cannot grow and spread. This is the one actionable common mechanism shared by all cancers. Cancer cells can use telomerase or alternative lengthening of telomeres (ALT) to extend telomere length, and while some research groups are working on telomerase inhibition, it is unfortunately the case that very few people are working on ALT. Since it has been demonstrated in mice that telomerase cancers can become ALT cancers, both approaches are needed to build a truly universal cancer treatment. Thus the SENS team has stepped in to fill the gap, and needs our help to raise the funds to make this happen.
I saw the article "Control ALT, Delete Cancer" about this project that you co-wrote in April, 2015. Why are you only now starting the crowdfunding effort?
Because we are now at the point where our hard work paid off and we were able to overcome most of the technical hurdles associated with making our novel ALT-specific assay compatible with robotic/automation methods. This is essential to performing high-throughput and large-scale screening studies. We will be measuring a particular biomarker that has only been observed in ALT cancers, namely C-circles, which are circular pieces of DNA containing a repetitive sequence only found at the ends of chromosomes (i.e., telomeres). The more ALT activity is present in a given cancer, the higher the levels of C-circles present in them. Therefore, once we exposed the ALT cancer cells to different compounds we will measure C-circle content quickly to assess if any of the compounds was able to inhibit the ALT pathway.
If your screening does find a promising compound, what do you plan to do with it? Will you patent its anti-ALT properties?
After exhaustive validation of the initial positive screening results, the next step will depend on the nature of the particular compound. If it is currently used in patients for cancer or any other indications we could approach the company that commercializes it to start a joint development program focused on ALT cancer therapy. Otherwise we will explore alternative ways of moving the development of these potential therapies into the private sector. We will absolute aim to patent any compounds that we find helpful in the fight against cancer whenever possible. It takes an average of 12 years for a compound to go from discovery to clinical use in the US. Now, it is possible to reduce that time significantly in case the promising compound we find in our screening is either already approved for clinical use or has been through extensive clinical trials. We will be testing such compounds as part of our screening as explained above. Alternatively, we could target initially ALT cancers that affect less than 200,000 patients in the US in order to obtain orphan drug designation, which can significantly expedite the approval process. This would pave the way for bringing therapies to more common ALT cancers.
How many other groups have also looked at ways to inhibit ALT?
There are very few research groups performing ALT-related cancer research worldwide, especially when you compare it to the amount of scientific output from telomerase-based cancer research efforts. Even within the research groups dedicating a lot of resources to ALT research, none of them to the best of our knowledge have the technical capability to perform such a large small molecule screening in the way we are planning to do it. Our technological achievement with the C-circle assay puts our group in a unique position to perform the largest screening study ever attempted in the field of ALT cancer research.