Updates on Single, Combination Precision Medicine in Targeted Cancer Therapy

May 1, 2020

In recent years, targeted cancer therapies have increased in use. These individualized treatments are based on the genetic makeup of a patient's disease.

Patients with the same type and stage of cancer have historially been administered the same treatment, despite variations in their responses to that treament. This approach, as discussed in Biomedicine & Pharmacotherapy, has been altered in recent years with the introduction of targeted cancer therapies that personalize treatment based on the genetic makeup of a patient’s cancer.

Precision medicine in cancer is characterized by these personalized therapies, and it is tailored to address potential genetic changes in a patient’s tumor. By directly attacking the tumor, the researchers stress the impact this can have in protecting healthy cells that are also damaged during chemotherapy and radiotherapy, which can lead to severe toxicity in healthy tissues.

The researchers sought to provide an outline of emerging developments in targeted cancer therapy, particularly 2 areas of interest: immune-based therapy and enzyme-/small molecules—based therapies. They included advancements in cancer targeted therapy, personalized medicine, and cancer combination therapies from research papers published from 2010 to June 2019.

Immune-Based Therapy

As the study authors discuss, immunotherapy-based strategies differ from both chemotherapy and radiotherapy-based treatments. Instead of directly attacking the growth of the cancer, the approach enhances the immune response to the cancer. Several notable innovations have increased the availability of this strategy, including immune checkpoint inhibitors (ICIs), immune cytokines, tumor-targeted superantigens, and ligand targeted therapeutics.

ICIs have served as major advancements in oncology, with several already approved by the FDA. Although their impact in revolutionizing the treatment of cancer has been noted, there have also been reports they could cause serious harm to patients due to their toxicity, with some recipients reporting immune-related adverse events. The researchers highlight that further studies are warranted to gain a detailed understanding of tumors' mechanisms of resistance to checkpoint inhibitors treatment, in order to improve the therapy.

Enzyme-/Small MoleculesBased Therapies

In enzyme-/small molecules—based therapies, the researchers cited innovations, such as the use of a proteolysis targeting chimera (PROTAC), antibody-drug conjugates, and antibody-directed enzyme prodrug therapy.

The PROTAC strategy has been expanded and utilized in the treatment of many diseases, including ER-positive breast cancer, and to target steroid hormone receptors for ubiquitination and degradation in breast and prostate cancers.

As the researchers note, the approach is inspired by a mechanism in which the cell degrades unwanted proteins and consists of a molecule with 2 independent moieties. Recently, PROTAC was used to degrade the anaplastic lymphoma kinase, which has been associated with several types of human cancer.

“The conventional therapeutic paradigm for cancer and other diseases has focused on a single type of intervention for all patients. However, a large literature in oncology supports the therapeutic benefits of a precision medicine approach to therapy as well as combination therapies,” said the study authors.

Reference

Bashraheel SS, Domling A, Goda SK. Update on targeted cancer therapies, single or in combination, and their fine tuning for precision medicine [published online February 25, 2020]. Biomed Pharmacother. doi: 10.1016/j.biopha.2020.110009.