Cancer – the hallmarks and beyond

Although cancer represents a huge challenge for our healthcare systems, new immunotherapies and other advanced novel treatments mean hope is on the horizon.

Cancer is one of the all-pervading topics that dominates conversations about the major challenges our healthcare system faces today. The WHO estimates that nearly 10 million people died from the disease in 2020, making it one of the leading causes of death worldwide[1]. This is partially attributable to our aging population, as longer lifespans increase the chance of accumulating genetic mutations that eventually lead to tumors. Counteracting this is improved access to early diagnostic testing: the last few decades have seen a revolution in cancer treatments, leading to smarter, more precise and personalized therapies than ever before.

Cancer is a complex disease that develops slowly over time. It relies on a sequence of subtle changes to our genes which alter the normal function of our cells. Our bodies have mechanisms to interfere or even prevent this from happening. They include mechanisms on the genetic level such as the mismatch repair mechanism where mutated DNA is recognized and replaced. Other mechanisms build on the immune system itself, which recognizes cancerous cells based on their surface molecules. However, cancer on the opposite has found several ways to avoid these mechanisms and also to escape detection by the immune system. Once a cancerous cell evades the body’s surveillance mechanisms, it begins to multiply rapidly, forming the characteristic mass of mutated cells known as a tumor.

Scientists Douglas Hanahan and Robert Weinberg produced a set of characteristics or ‘hallmarks’ of cancer in a 2000 paper which defined our common understanding of the disease nowadays. The paper describes how cancerous cells continue to change as they grow, acquiring more and more mutations as the normal brake mechanisms are switched off[2]. Eventually this snowball effect creates a tumor that can easily translocate from its origin and form metastases in distant organs.

The characteristics of cancer are diverse, with many different cell populations working together to form a complex mass. The lines between a tumor and normal cells are often blurred, as the tumor is able to recruit surrounding healthy cells and form new blood vessels to help keep it alive. In their follow-up publication to the original 2000 paper, Hanahan and Weinberg describe the importance of this interaction, showing the ‘tumor microenvironment’ to be a key – and previously underestimated – component of the disease[3]. In an update in 2022, the authors present provisional further dimensions of their concept of the complex journey human cells make on their way from normalcy to neoplastic growth[4].

Along with the diversity of cells within a tumor, the ability of cancers to migrate is crucial for spreading into distant organs. The tumor becomes more complex once the tumor cells become motile, moving away from the primary site and towards other areas of the body. Cancer that has migrated through the bloodstream is known as ‘metastatic’, deriving from the Greek word for ‘transition’. From this point onwards, the disease is much more challenging to treat, as surgery no longer is an option to clear the whole cancer.

With mutations occurring every day, it is logical to ask how our bodies protect us against this fatal process. The immune system can sense alterations occurring in cancer cells, recognizing them as ‘transformed cells’ rather than as healthy parts of the host. T cells play a vital role in this, constantly patrolling the body in search of potential threats[5]. In a similar manner to how the body fights off viruses and bacterial infections, our immune system has the ability to clear the cancer before it takes hold. The importance of this process is reflected in the recognition of a new hallmark, called ‘evading immune destruction’, which is seen as essential for tumor survival.

Although cancer represents a huge challenge for our healthcare systems, there is hope on the horizon. New immune therapies have significantly improved survival rates across cancers, and the technology continues to grow. A new focus on harnessing the power of the immune system will allow us to combat the disease in more ways than ever before.

Recent advances in cancer therapy combined with our knowledge of the immune system’s anti-tumor responses can lead to highly innovative solutions. This is the approach that invIOs is taking with its lead candidate treatment, APN401, which is currently in Phase 1b clinical trials.

APN401 combines cell therapy strategies with targeting the immune checkpoint inhibitor Cbl-b. It leverages the EPiC cell therapy delivery platform that invIOs is constantly improving, utilizing its knowledge of APN401 and targeting molecules to activate immune cell responses against various solid cancers.

EPiC is invIOs’ proprietary delivery platform that builds on the flexibility of RNAi technology. The platform aims to expand the applicability of cell therapy to additional checkpoints and holds enormous potential for new therapeutic approaches. APN401 has been demonstrated to be safe and well-tolerated during first-in-human clinical trials in patients with advanced state solid tumors.