Developing Treatments for Solid Cancers: Challenges and Opportunities

While the COVID-19 pandemic has dominated the headlines over the past two years, other diseases, such as cancer, continue to have devastating impacts on human health. Indeed, cancer claimed nearly 10 million lives in 2020 alone, and is the second leading cause of death worldwide.¹

One reason that cancer is so challenging to treat is that no two cancers are the same – each individual cancer has its own genetic identify with different biological characteristics. This heterogeneity is one of the major reasons that some cancer treatments fail or eventually lose their therapeutic effect.

Over the last 25 years, we’ve seen a significant shift in our approach to understanding the biology of solid cancers, which are abnormal masses of malignant cells found in organs, muscle, and bone. While research previously focused on the individual tumor cells, scientists are now viewing the tumor as a complex and dynamic organ, and the tumor microenvironment has gained increased attention for drug intervention strategies.

Solid tumors can be grouped into two main categories:

• Carcinomas, which form in the epithelial lining of organs, skin, or glands. This is the most common type of cancer, accounting for around 80-90% of all cancer cases.²
• Sarcomas, which form in supportive tissue such as bone, muscle, tendons, and blood or lymph vessels. Sarcomas are relatively rare in adults and make up approximately 1% of all adult cancer diagnoses.³

Compared with liquid cancers, solid tumors present a unique set of challenges to researchers, including a lack of expression of tumor-specific antigen targets and a metabolically challenging and highly immunosuppressive tumor microenvironment.

 Shifting Research Focus

Despite these challenges, advances in genetics and genomics, sequencing technologies, single-cell analysis, and tumor models have revealed complex mutation signatures or alterations in genetic profiles of individual solid cancers, opening up the possibility of personalized treatment approaches. It has also helped identify key signaling pathways involved in tumor survival and progression.

For example, research has shown that mutations in the genes encoding epidermal growth factor receptor (EGFR) play an important role in the progression and metastasis of non-small cell lung carcinoma (NSCLC) – one of the most common types of lung cancer. This has led researchers to develop tyrosine kinase inhibitors (TKIs) of EGFR, which bind to EGFR and prevent cell proliferation, ultimately leading to cell death. Currently, first-, second- and third-generation EGFR TKIs are available for the treatment of EGFR-mutant NSCLC patients, and EGFR TKI combination therapies are also being explored.

Another approach that has revolutionized solid cancer treatment in recent years is immunotherapy, which utilizes a patient’s own natural immune response to selectively target cancer cells. There are several types of immunotherapy, including immune checkpoint inhibitors, CAR T-cell therapies, and monoclonal antibodies (mAbs).

Progress in antibody engineering and manufacturing techniques has meant that bispecific antibodies (BsAbs) are now a realistic possibility in cancer immunotherapy. BsAbs have the ability to bind two different antigens, and so can be developed to precisely target and reactivate immune cells, promoting tumor cell lysis and a return to immune homeostasis.

 The Future of Solid Cancers

It is clear that further work is urgently needed to help advance cancer research and discovery and develop effective treatments for solid tumors. A deeper understanding of the genes and pathways altered in cancer will help identify potential targets for treatment, while appropriate cell-based assays can help determine the cellular responses to various drug treatments.

Our latest literature review highlights two examples of solid tumors – NSCLC and soft tissue sarcoma (STS) – and the types of assays that are being utilized by research groups to characterize and develop new treatments targeting solid cancers.

References

1. Cancer [Internet]. Who.int. 2021 [cited 9 November 2021]. Available from: https://www.who.int/news-room/fact-sheets/detail/cancer
2. Cancer Classification | SEER Training [Internet]. Training.seer.cancer.gov. 2021 [cited 24 August 2021]. Available from: https://training.seer.cancer.gov/disease/categories/classification.html#carcinoma
3. Sarcoma [Internet]. NFCR. 2021 [cited 24 August 2021]. Available from: https://www.nfcr.org/cancer-types/sarcoma/