The year 2018 was a notable one for the cancer research community and our quest to prevent, detect and treat cancer. Fueled largely by our nation’s continued investment in basic and applied biomedical research, significant progress has occurred in areas of targeted and immune therapy as well as molecular diagnostics. Below is a ‘top ten’ list of recent notable advances, which are dominated by immunotherapy, a form of therapy that enlists the immune system to recognize and kill cancer cells. The widespread transformative impact of cancer immunotherapy is reflected by the awarding of this year’s Nobel Prize in Medicine or Physiology for the discovery of immune checkpoint blockade inhibitor drugs. Here are some of the most notable advances in the cancer field.
- The approval of CD19 CAR-T, a cell-based immune therapy in which T cells are engineered to recognize antigens present on the surface of a cancer cell. This approval heralded the first cellular therapy as a standard of care in cancer.
- Tumor mutational burden became a predictive biomarker for responses to checkpoint blockade inhibitor therapy. Such biomarkers will improve the application of these novel therapies to cancer patients who are more likely to respond. As importantly, non-responder patients are spared both the financial burden of ineffective therapy as well as the potential side effects of the therapy.
- Early studies of cancer vaccine approaches, designed to stimulate immune responses against cancer-specific targets, show promise in melanoma, glioblastoma, and HPV-associated cancers. This approach is based on our expanding knowledge of cancer-specific antigens that can be recognized by the immune system.
- This past year was a banner year for acute myeloid leukemia (AML) with the approval of two new classes of cancer drugs: Venetoclax, a BCL2 antagonist that blocks critical protein-protein interaction to spur cancer cell apoptosis and an IDH1 inhibitor that targets metabolism. While unrelated to AML, advances in cancer cell metabolism included dietary modifications (so-called ketogenic diet) as a means of enhancing responses to certain therapies targeting cancer metabolism.
- A molecular detection test for human papilloma virus (HPV – the virus drives the development of cervical cancer) becomes a standard diagnostic test for the identification of high-risk HPV cases. This test may replace the longstanding PAP smear as a routine diagnostic for cervical cancer risk. PapSEEK
- The first of many combinations of anti-PD1 with targeted agents was approved for renal cell carcinoma with the synergistic combination of anti-PD1 and various anti-angiogenesis therapies.
- An entirely new class of drugs, stapled peptides, which disrupt MDM2 and MDM4 function, saw some anti-cancer activity based on interim data from phase 1/1b clinical trials.
- This past year, research has revealed important interactions between the gut microbiome and cancer therapeutic drugs. The composition of a patient’s microbiome can influence their response or non-response to immunotherapy, suggesting that bacteria mediate interactions with the immune system that are essential for drug efficacy. Gut microbes may also affect responses to other forms of therapy, and may additionally influence toxicities — areas of growing interest.
- Single Cell Sequencing (SCS) was chosen by the journal Scienceas its “2018 Breakthrough of the Year.” Researchers are using SCS approaches to characterize the genetic and functional properties of individual patient cells in both normal tissue and tumors, leading to clinical opportunities, including in breast cancer where SCS was able to identify pre-existing tumor cells containing mutations that would lead to therapeutic resistance [Kim et al.], and has facilitated detailed tumor biology [Casasent et al.] that could impact on patient treatment.
- Like MMR and PD1 in 2017, in 2018 another tumor agnostic therapy emerged for TRK fusions. The FDA approved Vitrakvi(larotrectinib)for the treatment of any cancer type that contains NTRKfusions, not specifically focusing on a given cancer type. Treatment of patients who have NTRK fusion-positive cancers with a first-generation TRK inhibitor such as larotrectinib, has shown high response rates of greater that 75%.