Targeted Cancer Therapies

“One-Size-DOES NOT-Fit-All” ‘You wouldn’t wear just any pair of glasses – your prescription is tailored to your vision’1. This statement alludes to and embraces the importance of an individual’s unique characteristics: genetics, health history, lifestyle, diet, or geographic location. Just as you would expect your doctor to match a blood transfusion to a blood type, wouldn’t you want your health care tailored uniquely to you in other ways if that were possible? The answer is likely YES. This is the foundation of precision medicine, a customized treatment plan based on an individual’s unique characteristics and developed using advanced technology. How Does Precision Medicine Use Advanced Technology to Match a Cancer Treatment to a Patient? While all humans are alike, variations in DNA blueprints are what differentiate one from another, and in certain individuals those variations may be the root cause of some illnesses, including cancer. Modern computational technology has made it possible for scientists to analyze the gigantic sets of codes in our DNA that affect human health and to identify tiny variations in that code. This is Precision Medicine. How Does Targeted Therapy Rely on Precision Medicine? Because cancer may be considered a disease of genomics, or one’s DNA, we now have the technology and knowledge to pinpoint where the change in genomics occurred and caused certain cancers. This helps us to design cancer treatments specifically targeting those abnormalities in cancer cells without harming adjacent normal cells. This is Targeted Therapy. As an example, scientists have learned the genomic alteration related to lung cancer patients and are exploring how using targeted therapy shapes the way we treat lung cancer. One of the genes that is abnormal and might cause cancer is MET (c-MET; MET-EXON 14)2. What Is MET and How is it Related to Cancer? c-MET is a protein (MET gene) we all have in our body that plays a role in normal cell growth. Sometimes, for an unknown reason, MET gets altered and can contribute to cancer. Recent research suggests that these alterations in the MET gene (e.g., Exon 14 skipping, amplification or fusion) are often found in patients with lung cancer and other types of solid tumor cancers. Therefore, inhibiting abnormal MET pathways is considered an important focus area for developing new targeted therapies. A Clinical Trial Targeting MET The SPARTA Clinical Trial is exploring an investigational drug (APL-101) that targets tumor cells expressing one or more MET genetic abnormalities in hopes to cause tumor cell death and shrink or halt cancer cell growth in various advanced cancer types. APL-101 has been studied in participants with advanced solid tumors (including glioblastoma; gastrointestinal cancers; lung cancer) in a Phase 1/2 global clinical trial enrolling in 14 countries around the world3. To be eligible for the SPARTA Study, patients must qualify for the prerequisite criteria including a diagnosis with advanced tumors and have one (or more) of the following alterations in their MET gene: MET Exon 14 skipping mutation, MET Amplification, MET-gene Fusions. To learn more about investigational options for patients with MET aberrated cancers, visit: https://spartacancertrial.com/. You should consult your doctor to discuss the possible benefits and ways [...]

Triple-negative breast cancer (TNBC) is more aggressive and has a worse prognosis than other breast cancers. Triple-negative breast cancer (TNBC) accounts for about 15-20% of all breast cancers. The word "triple-negative" means laboratory test results for the three treatment targets on cancer cells, namely the estrogen receptors, progesterone receptors, and HER2 proteins, are all negative. TNBC is a more aggressive type of cancer that grows and spreads faster. As the triple-negative cancer cells won't respond well to most therapies, including hormone therapy and targeted therapy, doctors have very few treatment options to control the cancer progress. As a result, TNBC patients tend to spread faster and have a higher recurrence rate and worse prognosis. A New Treatment Option is Now Available On March 11, 2022, the Food and Drug Administration (FDA) approved a drug called Olaparib to treat HER2-negative, high-risk early breast cancer. Data from a phase 3 clinical trial of 1,836 patients, of which about 82% had the triple-negative disease, led to the approval. The clinical trial results demonstrated that Olaparib reduced the risk of death by 32%, compared to the placebo. The recent FDA approval brings new hopes to patients with early triple-negative breast cancer since many currently available therapies couldn't effectively control the progression of their cancers. Patients have to do a blood test before receiving Olaparib treatment. Olaparib is a targeted therapy restricted to patients whose breast cancers have specific gene mutations called germline BRCA1/2 mutations. To be eligible for the treatment, patients must have an FDA-approved blood test, or a companion diagnostic test, to confirm the existence of the germline BRCA1/2 mutations before their treatment. Patients without the confirmed mutations couldn't receive the Olaparib treatment as they won't have the treatment benefits from the drug and might experience the drug's harsher side effects. Research Performed Three Decades Ago Enhances Targeted Therapy Today  In 1990, Dr. Mary-Claire King, an assistant professor at UC Berkeley, was the first scientist to demonstrate that a gene on chromosome 17q21, named BRCA1 one year later, was responsible for hereditary early-onset breast cancers. In 1994, Drs. Michael Stratton and Richard Wooster in the UK identified BRCA2. Three decades later, mutations in the BRCA1 and BRCA2 genes become a critical indication to enhance the targeted therapy with Olaparib. It tells us that converting research discoveries to patient-impacting benefits takes pretty long. We need to continue to support basic research today so that new therapies can continue to save patients' lives in the future. To recognize Dr. Mary-Claire King's fundamental contribution to the genetic understanding of cancer, the National Foundation for Cancer Research (NFCR) awarded Dr. Mary-Claire King the Szent-Györgyi Prize for Progress in Cancer Research in 2016 in Washington DC. Learn more about this award and Dr. Mary-Claire King's research here. Olaparib offers survival benefits and brings new hopes to patients with early triple-negative breast cancer. As the patients have to be selected by an FDA-approved blood test before the treatment, patients should work with their doctors to determine whether they are eligible for the treatment before receiving the treatment. Sign up here to receive our monthly e-newsletter featuring healthy living information, stories of [...]

“The essence of precision medicine, in particular precision oncology, is to make cancer management more precise based on genomic mapping and molecular characterization of the unique tumors for each patient,” says Dr. Wei Zhang. “The cancer management that needs to be precision include diagnosis, prognosis, treatment plan, treatment monitoring, and genetic counseling.” Precision medicine, and by extension, oncology, is the buzzword of the moment among doctors and researchers, and it is more than just spin or a fad. With regards to cancer, and as our understanding of the disease has increased, the idea of a one-drug-cures-all panacea is now widely considered obsolete (however much of a holy grail such would be). Cancer, even the same type, varies at a genetic level from patient to patient. The therapies that work with “Patient A” may not at all with “Patient B,” due at least in part in the natural genetic difference that exists among practically all living things. Zhang admits the field is still in its infancy, the promise it holds is vast: with the rise of genomics, scientists can untangle the genetic knot of cancer, tailoring customized treatment regimens unique to a person, start to finish. Trailblazing cancer research for the last 20 years, Zhang has been witness to the evolution of cancer treatment, at one point co-directing a Genome Data Analysis Center under the National Cancer Institute-funded Cancer Genome Atlas program. He also served as Director of the Cancer Systems Biology Center funded by the National Foundation for Cancer Research for several years when at the MD Anderson Cancer Center. In 2016, he was recruited to the Wake Forest Comprehensive Cancer Center located in Winston Salem, North Carolina to lead the Center for Cancer Genomics and Precision Oncology and takes a direct role in the development of targeted therapies. Moreover, Zhang, who is also an NFCR Fellow, instituted sorely-needed diversity in cancer research. While cancer is not particularly picky, some forms of it tend to show up more in specific ethnicities that, historically, were overlooked, often with great detriment: African-Americans have the highest death rate and shortest survival of any racial and ethnic group in the USA for most cancers. “Our precision medicine/oncology considers health disparities a priority issue of our cancer center,” Zhang explains. “In our program, 14 percent of all cancer patients who are enrolled in our precision oncology trials are African-American patients, a percentage that is much higher than most cancer centers in the country. We have taken on a leading role in our effort in understanding the unique genomics features for cancer of African-American ancestry.” For all its promise, Zhang stressed that precision medicine, and oncology, is still in its infancy. The single most rate-limiting challenge is the effective matching of genomic mutations with corresponding drugs. That being said, precision medicine/oncology is for everyone involved in cancer management. That includes patients and family members, doctors, researchers, pharmaceutical companies, funding agencies and insurance industries.  Decisions have to be made through better research and better development of targeted therapeutics. Zhang is optimistic. “The efficacy will continue to improve with the effort of national consortium such as Precision Medicine [...]