Molecular targeted therapy: Bringing specificity to cancer treatment
By Dr. Sourabh Radhakrishnan, Senior Consultant and Director Medical Oncology and HSCT, Karkinos Healthcare Services
Cancer is a disease that manifests with several variations. Unlike other diseases, cancer cause cannot be predicted based on general examination. A detailed study at the genome level combined with precise imaging is required to identify the type of cancer and its stage in the body.
The way the disease causes its effects varies from person to person. Two different people suffering Stage II breast cancer present the disease in two different ways or severities. This is because of the type of gene mutation occurring in the breast cells that result in tumor growth that is genetically led to either metastasize or limit itself. Like, in invasive breast cancer, researchers have identified five main molecular subtypes, which are based on the genes the cancer cells express.
Understanding such molecular expression of the cancer cells is critical in precision oncology that targets specific genetic characteristics of a tumor. The understanding also helps in incorporating the knowledge into designing cancer treatment protocols. In this way, existing therapies can be “tailored” to avoid side effects and save money on expensive or ineffective treatments. This breakthrough has intrigued the interests of several researchers around the world and now it represents a new horizon in cancer treatment.
Molecular profiling has a strong influence on every aspect of cancer care including detection, diagnosis, staging and therapy response assessment. Recent advances in the understanding of cancer biology have prompted the introduction of new targeted therapy approaches. Many molecular targeted therapies approved by the US Food and Drug Administration (FDA) have demonstrated remarkable clinical success in the treatment of a myriad of cancer types including breast, leukemia, colorectal, lung, and ovarian cancers.
Targeted cancer therapy
Targeted therapy is a type of cancer treatment that uses drugs designed to target cancer cells without affecting normal cells. This is the ground for personalized medicine or precision medicine. The drugs are designed to have the ability to target specific changes or substances in cancer cells, and these targets, as said earlier, can be different even when people have the same type of cancer.
To identify changes at the genome level, mutational testing is now widely adopted. Certain types of tumors are tested for different targets after a biopsy or surgery. The changes can be at the DNA, RNA, protein, or metabolomic profiles that are specific to a tumor. Testing can also include genomic testing to look at the DNA sequence, DNA or RNA to look for gene fusions, or tests to measure RNA or protein levels. For example, the presence of BRCA1 and BRCA2 gene mutations have prognostic implications on breast or ovarian cancers; HER2 protein overexpression can have prognostic implications on breast, ovarian, bladder, pancreatic, or stomach cancers; etc.
Molecular testing, therefore, can be used to assess an individual’s risk of developing cancer or to determine an individual’s risk of cancer recurrence. These gene mutations are valued more to design a therapy or a combination of therapies for a specific patient. They are also key to developing new targeted drugs that can save lives. The other major advantage is to administer targeted drugs over drugs delivered through chemotherapy. It is known that chemotherapy has several side effects as normal cells are most likely to be damaged while administering the drug.
Scaling Karkinos Healthcare’s diagnostic capabilities
There is a lot of focus on developing new targeted therapy drugs that disrupt the key drivers of cancer growth, but not all cancer types currently have identifiable changes in the gene expression. Research has shown that treatment that is led by molecular testing can not only extend patients’ lives but also help them from facing the side effects of existing cancer treatments. Hence, cancer researchers believe that the future beholds a lot of research interest.
To improve the molecular diagnostic-based capabilities of the country and as well make cancer care cost-effective and equitable, Karkinos Healthcare has established its Advanced Center for Cancer Diagnostics and Research (ACCDR) and the Centre for Biomedical Research, Innovation and Commercialisation in Cancer (BRIC).
While the ACCDR is a state-of-the-art lab and a one-stop solution for all diagnostics related to cancer, including histopathology, Immunohistochemistry (IHC), Fluorescence in situ Hybridisation (FISH), molecular tests and gene sequencing, the Center for Biomedical Research, Innovation and Commercialisation in Cancer (BRIC) focuses on technology research and in establishing an innovation ecosystem for cancers.
The ACCDR serves as a central lab for Karkinos Healthcare’s global oncology network, analyzing specimens at molecular and genomic level to aid in personalized targeted therapy, predicting possible response to treatment as well as to evaluate response by liquid biopsy. The focus is on early diagnostic tools, molecular assays for precision medicine, which are not readily available in the country.
Karkinos Healthcare has installed the most advanced high-throughput HPV assay equipment Cobas 6800 in this center with the ability to test over 1200 Human Papilloma Virus (HPV) assays of all high-risk types.
The other major goal set by ACCDR and BRIC is to establish an Indian genomic cancer map. As the cancers in our country have their own genomic footprint, different from the western countries, Karkinos Healthcare believes in investing in the Whole Genome Sequencing (WGS) method to enable the creation of India-specific cancer atlas that has immense research potential to derive the knowledge about cancers and the way to bring down the disease’s burden in India.
The commitment to reduce the cancer burden in India has led Karkinos Healthcare to associate, collaborate, and partner with global academic institutions and hospitals. Premier American medical institution Mayo Clinic has invested a minority stake in the company to further cancer research, and C2i Genomics, a cancer intelligence company, has entered into a strategic partnership with Karkinos Healthcare to co-develop the minimal residual disease (MRD) market in India. Recently, IIT Guwahati partnered with Karkinos Healthcare to establish a Center of Advanced Research on Diagnostics in Cancer (C-CARD), which will be equipped and operated by Karkinos at the IIT Guwahati premises. The primary aim of this center is to work on research related to advanced and affordable cancer diagnostics solutions. The company is also bringing into its Distributed Cancer Care Network (DCCN) several hospitals and Primary Health Care service providers to increase the accessibility of cancer screening, diagnosis, and treatment.