A Bull’s Eye Approach for Targeted Cancer Therapies
Collaboration is at the heart of developing and deploying new targeted cancer solutions
Mark Garner received his PhD in biochemistry from Michigan State University. As part of his graduate work, Mark invented the now universally used gel-shift or “EMSA” assay for the study of protein–DNA interactions. Mark was then successively an American Cancer Society postdoctoral fellow and National Research Service Awardee at the NIH, and also completed a second postdoc at the University of Wisconsin-Madison. During this time, Mark also developed a long-term relationship with the Max Planck Institut für Biophysikalische Chemie in Göttingen. Mark returned to the NIH where he carried out fundamental research on capillary electrophoresis of nucleic acids and the molecular biophysics of macromolecular crowding and its effects on cellular processes. Since entering the private sector, Mark has worked with several cutting-edge companies and is currently global cancer segment manager with Agilent Technologies. Mark is based in Toronto, Canada.
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Revolutions often start behind closed doors, especially in medicine. In particular, a significant leap is happening in cancer research, where results from the last 20 years are beginning to shed new light on some of the most intransigent problems in the field.
Researchers are starting to create a comprehensive picture of the disease, including chains of causality, by connecting data from genomics, single-cell analysis, metabolic studies, and protein profiling. These insights provide unprecedented insight into biological events and cellular signaling processes in cancer, opening new doors for targeted cancer therapies.
Precision oncology: refining the approach to cancer treatment
The brute force of conventional chemotherapy kills almost every rapidly dividing cell, including healthy ones. This means a round of treatment is a race to eradicate the tumor before the side effects become intolerable for the patient, a situation far from ideal. Fortunately, precision oncology is giving clinicians and patients more options.
What is precision oncology?Precision oncology is a targeted type of medicine based on the molecular characteristics of a patient’s cancer, such as genes and/or proteins expressed by the tumor. Precision oncology allows clinicians to target therapeutics to a cancer’s precise molecular phenotype to destroy it. |
Companion diagnostics, or CDx, diagnostic tests that guide precision therapeutic selection, assist with this molecular characterization. Companies developing CDx tests often collaborate closely with pharmaceutical companies as they characterize the molecular phenotype of specific cancers to find companion diagnostics to predict against which tumors a therapy will be effective.
The field of companion diagnostics for therapy selection has expanded to offer patients minimally invasive testing through liquid biopsy. As tumors grow, some cells die and shed small fragments of DNA into the bloodstream. Tumor DNA can be isolated within the plasma of a simple blood draw. Although not as sensitive as classic tissue biopsy techniques, liquid biopsies are more straightforward and less invasive than conventional biopsies—even fine needle aspirates—and multiple blood samples can be taken throughout treatment.
Loading the cart with cancer killers
The human body has many mechanisms to prevent or reverse damage. The concept of immune surveillance, i.e., the immune system’s capacity to prevent cancer by finding and killing developing cancer cells before a tumor can form, was first articulated in the 1960s. All cancer immunotherapy aims to enhance the human body’s natural ability to detect and kill cancer cells.
In adoptive cell therapy, T cells harvested from a patient are genetically engineered to recognize and kill cancer cells more effectively—in the case of CAR-T cells, this is a chimeric antigen receptor. To date, adoptive cell therapy has only been successful against blood cancers, but many scientists and physicians are working on extending this novel therapy to solid tumors.
The process of developing CAR-T cell therapies includes selecting T cells using genomics solutions, and measuring their metabolic fitness, potency, persistence in killing, and readiness to go back into the patient. The process must be done quickly, usually within a couple of weeks, as a patient’s immune system is compromised when the cells are removed. Time is of the essence.
The tumor microenvironment
The interaction between the immune system and cancer can be thought of as a predator–prey relationship: the tumor constantly develops mechanisms for hiding from or diminishing the immune system. A tumor is not just a fast-growing ball of normal cells, it’s heterogeneous at the cellular level.
The tumor microenvironment is one of the mechanisms a tumor uses to evade the immune system. Tumor cells excrete metabolites that modulate or suppress the immune cells’ response. Many cancer researchers are using cell analysis and mass spectrometry instrumentation to more clearly understand these mechanisms and how to design therapies to overcome this defense.
Treating the patient as an individual requires that everything come together: targeted immunotherapy coupled with precision and companion diagnostics. With the latest advances, options are now available that negate the need to take a brute-force approach every time.
Integrated solutions
Providing cancer researchers with an integrated portfolio of solutions, from initial research, including NGS and cancer cell metabolism characterization or protein analysis, to precision oncology, enables the study of the profoundly altered cell metabolism and metabolic reprogramming characteristic of cancer cells.
In addition, mass spectrometry solutions deliver an understanding of the physiology of cancer cells and the mechanisms that enable a cancer cell to grow so fast. These solutions help researchers understand how tumor cells change the response of immune cells in the microenvironment.
Integrated solutions for primary, special, and advanced tissue staining are also invaluable, including reagents, protocols, instruments, and software designed to work together to help pathology labs and clinicians provide accurate and timely diagnostic results and the most effective treatment plans for cancer patients.
A commitment to collaboration
Companies collaborating with the cancer research community to develop and deploy new tools and workflow solutions are making a difference. Combined with integrative thinking based on extensive experience, these wide-ranging collaborations enable a better understanding of researchers’ needs at a profound level, providing trusted answers that give researchers certainty in their results and make confident diagnostic decisions.
Nothing can replace rigorous, peer-reviewed research and publications to verify the value of a technology. When it comes to cancer research, nothing less is acceptable. The scientific community strives every day to work to deliver on that promise. Because in the fight against cancer, every day counts.