Precision Medicine and Immune-Oncology Transform Cancer Treatment

The recent progress and growth in cancer treatment with precision medicine and immuno-oncology is now being applied to cancer detection and prevention.

The extraordinary recent advances in genome-wide sequencing, big-data analytics, blood-based technologies, and a deep understanding of the tumor immune microenvironment (TME), has provided unprecedented possibilities to study and apply these advances to the biology of premalignancy.

Recent Achievements

In Cancer Prevention Research (January 2016), Thomas Kensler et al reported a robust list of just some of the key achievements in 2015. They include:

• Driver mutations detected in circulating cell-free DNA in patients with premalignant lesions (lung)
• Clonal hematopoiesis shown to be a premalignant state
• Molecular selection in chemoprevention randomized controlled trial (RCT; oral)
• Striking efficacy in RCT of combination chemoprevention targeting signaling pathway alterations mechanistically linked to germline mutation (duodenum)
• Molecular markers for early detection validated for lung cancer and showing promise for pancreatic, liver, and ovarian cancer
• Recent mechanistic studies of repurposed drugs such as aspirin, metformin, and tamoxifen have identified potent immune activity

Another key achievement has been the identification of HPV as the essential cause of a major global cancer burden, including HPV16 as the single driver of an epidemic of oropharyngeal cancer in men. This advancement provides unique opportunities for the dissemination and implementation of public health interventions.

Emerging Technologies

A small sample of technologies on the horizon of cancer detection and prevention include:

• Biology of premalignancy

While focus on the molecular origins of cancer has increased over the last several years, in contrast to studies in malignancy, genome-wide analyses of premalignancy have been rare. With remarkable technological advances in next-generation sequencing (NGS), among other technologies, we now have very real possibilities to deeply probe the biology of premalignancy.

• Immunoprevention: viral vaccines

A successful example of immunoprevention is the nationwide hepatitis B virus (HBV) vaccination program in Taiwan that began in 1984, which produced an 80% reduction in the incidence of hepatocellular carcinoma.

The standard 3-dose schedule of prophylactic HPV vaccine given before infection has 90—100% efficacy in preventing HPV infection and associated anogenital neoplasia. Additionally, limited data from secondary analysis of RCT in women reported vaccine protection for oral HPV infection implicated in oropharyngeal cancer.

• Implementation Science

More than 50% of cancers are preventable through lifestyle modifications, including increased physical activity, reduced obesity, and elimination of cigarette smoking. Standard screening tests are unevenly distributed from state to state and also county to county.

Greater use and funding of effective medical interventions across all sectors of society adds to the potential to prevent the majority of cancer and reduce these disparities.

Given that the global burden of cancer is enormous and increasing (the number of diagnosed cases is expected to grow worldwide from 13.3 million in 2010 to 20 million by 2030; ref. 6), cancer prevention, including early detection, is essential to our ability to lessen the burden of cancer in our lifetime.