Precision oncology and cancer cure by immunotherapy

Every year 4th February is observed as the "World Cancer Day", adopted by Union for International Cancer Control UICC in 2000 at Paris World summit against cancer with the aim to create awareness, promote prevention and to reduce death from cancer. This is the second year of the World Cancer day campaign 2025-2027, "United by Unique", a three-year journey from raising awareness to taking people centered action. That means people are at the centre of care, every cancer patient has unique story, undergone experiences that are very unique, and if we united all those stories, we will be able to look beyond the diseases and explore new ways of making a difference in treatment and care.
World cancer burden: Despite the various activities and campaign throughout the world over the last 25 years, the incidence of cancers is exponentially increasing, afflicting millions of people irrespective of age, sex, race and religion worldwide. Now the world is facing catastrophic healthcare challenges because of growing cancer burden in different communities and countries. According to IACR, the global incidence of cancer is more than 24 million new cases with 9.7 million deaths. which are predicted to rise 61% over the next 25 years to 35 million globally by 2050, majority in Low and middle income (LMIC) countries. Even in USA, with over 2.1 million new cases, 626,000 deaths are projected in 2026. In South East the cancer burden is tremendous high because of densely populated regions with low hygiene conditions, high rate of infections and air pollution. In Bangladesh, though there is yet no national registry, based on studies by National Institute for Cancer Research and Hospital (NICRH), 11% of the total population approximately 12.6 million, are under immense suffering from various forms of cancer creating with a huge socioeconomical burden. The multiple environmental factors for rising cancer burden are the vicious circle of unhealthy diets, food adulteration and processed foods, sedentary unhygienic life styles with air pollutions.
New concept of cancer: Our knowledge of cancer has greatly improved in the last two decades. Understanding of the complexity of human body which is made of cells, an estimated total of 37 trillion cells are constantly working in our body keeping us alive and active. Each cells type has a unique function with 46 chromosomes within the nucleus of the cells that are packed in chromatin bundles that contain DNA codes or genomic codes. These genomic codes are responsible for all information and instruction for making proteins, enzymes, hormones responsible for growth, metabolism and immunity keeping us healthy, dynamic and protect us from diseases. Cancer is a complex disease due to multiple changes in these DNA codes, these changes are scientifically known as DNA mutations. Most of the time, DNA changes can be corrected by DNA damage repair systems within our cells. When these changes or mutations in genomic codes cause genetic instability in a single cell, that results in transformation of a normal cell into malignant cells. These genetic changes could occur at DNA, RNA or at protein level and lead upregulation of cellular signaling pathways with the emergence of continuously growing cancer cells. Also changes in DNA sequences result in activation of Oncogene causing cancer. Mutation in Tumor Suppressor Gene leads to upregulation of cellular signaling pathways with uncontrolled proliferation cells forming a "tumor or lump" within any organ. That is why cancer can occur in any cell in anywhere in the body including bloodforming cells leukemias and lymphomas, or in any solid organ like Breast, Lung, gastric, colon, prostate, thyroid cancer including skin. Hyperactive dynamic malignant cells do not remain confined with the primary organ of origin, rather have the ability to invade into the surrounding tissues as well as spread to distant areas of the body in the form of metastases resulting in functional disturbance, organ failure and high mortality in cancer.
Detection of cancer: With the tremendous advancement of medical science and application of biotechnologies in medical detection and genomic researches revealed that every person's cancer is comprised of a unique combination of genetically inherited gene mutations and cell transformation that have been driven mostly by environmental factors, result of lifestyle choices and diets. In other words, your cancer is truly unique to you. Cancer detection involves regular screening tests, mammogram, colonoscopies, imaging CT, MRI, including tissue biopsies. Advances in multiple fronts on molecular diagnosis and molecular subtype of cancers, multicancer early detection tests, cell free DNA analysis, liquid biopsies are increasingly making cancer earlier and precisely detected before it spreads to other sites. Even with advancing in imaging technologies PET Scan, metastasis of cancer can be detected. For many patients, cancer is increasingly becoming a treatable, manageable condition rather than an immediate death sentence. Early detection significantly improves survival rates. With more options available, patients will be able to get all therapies that are specific to their needs.
Despite progress in detection, and effective new treatment, cancer remains a leading cause of death. There are still many unmet needs in cancer, curing cancer is certainly one of the big challenges of the 21st century.
Precision oncology: Precision oncology is an innovative personalized approach to cancer treatment that ensures your treatment is specifically designed and targeted to your unique form of cancer. Each patient's cancer is complex and unique. By combining genomic sciences and disparities in cancer research, scientists are identifying customized care plans with the main goal to provide the "right treatment to the right patient at the right time," Precision Oncology tailors medical decisions and therapies to the individual characteristics of each patient and their specific tumor. It's the science of using each patient's individual genetic, proteomic, and metabolic profile to select the most effective treatment. First by using advanced technology, genes that are mutated, causing their cancer to grow, are identified to create a treatment protocol selecting the best cancer treatment and care for that person. Mostly it involves analyzing a patient's tumor DNA mutation analysis, and sometimes RNA or proteins to find specific DNA mutation, then matching them with targeted drugs or check point inhibitors and immunotherapies, offering customized care for better outcomes.
An individual's unique genetic makeup and tumor's molecular profile, by targeting specific treatable mutation to move beyond broad cancer categories to a highly specific, individualized care, rather than a one-size-fits-all method. Molecular testing is widely used to detect these genetic changes and find treatable mutations. By identifying specific DNA mutations with application of biotechnologies in diagnostic tools, new advanced treatments protocol is aiming for more effective treatments with fewer side effects.
Genetic samples can be collected in several different ways, for instance, analyze of tumor biopsy and blood samples. To combat the challenge of the complex disease cancer, early detection and diagnosis of cancer at molecular level is fundamental. The ultimate fulfillment of precision oncology is to deliver the most effective cancer treatment for a patient's unique cancer, at a hyper-precise dose and at the right time to maximize survival and quality of life.
Core components of precision oncology:
• Genetic Profiling: Doctors use DNA mutation analysis to identify "driver mutations" -- specific changes in DNA that cause cancer cells to grow.
• Confirmation of the molecular subtype of cancer on sufficient tumor tissue by Immune histochemical staining IMS and detection of tumor burden by circulating tumor cell numbers and Immunoassay of serum tumor markers or biomarkers.
• Confirmation of the diagnosis of cancer using molecular devices such as Mutation Analysis by PCR, Geno- typing, detection of Oncogene/P53 mutation pattern and corresponding Cellular Signaling and Next generation sequencing (NGS) if needed.
• Molecular Tumor Boards: Multidisciplinary teams of Surgical Oncologists, Primary Oncologist Histopathologists, and bioinformaticians review a patient's genomic data to recommend personalized treatment plans.
• Liquid Biopsies: A non-invasive method using blood samples to detect circulating tumor DNA (ctDNA), allowing doctors to monitor treatment response and resistance in real-time.
Advanced new treatment for cancer: Personalized management is considered as the future of cancer care. "Precision Oncology" aims to individualize treatments with Targeted therapies and Immunotherapies by assessing the patients' unique genetic alterations. Targeted therapies are "precision medicines," are available drugs that have been designed to only attack the mutated cells. Because these targeted drugs leave healthy cells alone, they produce higher survival rates than standard chemotherapy and radiation.
Examples of targeted therapies: These are drugs trastuzumab Herceptin, Pertuzumab Perzeta designed to attack specific molecular targets like the HER2 protein in breast cancer or any other solid tumor expressing HER-2 protein. Targeting BCR-ABL in leukemia while sparing healthy cells. The ability to test for HER2 positivity as defined as fluorescent in situ hybridization-gene amplification or immunohistochemistry to demonstrate overexpression of the HER-2 protein is essential. Positive results predicted response to trastuzumab-based therapies, whereas HER2-negative tumors did not derive benefit from this approach.
Surgical management followed by conventional chemo-radiotherapy are not sufficient to improve survival rate, rather development of Chemo-Radio resistant leads to aggressive phenotype with high recurrence rate. "Targeted Therapy" and Immune check point inhibitors, Immunotherapy ensure complete cure from Breast Cancer and some other Cancer so far.
Immunotherapy and immune based cell therapy for cancer: Another powerful option for killing cancer cells is all along using the body's immune system. Our immune system's natural ability to detect and destroy abnormal cells prevents many cancers from ever developing, just like it protects us from infections. However, cancer cells can evade this system of immune surveillance. In this new field of cancer immunotherapy, cancer cells are destroyed with drugs using body's immune cells to control and, in some cases, even cure their cancer. Because the treatments enlist the immune system, they do not kill normal dividing cell like traditional chemotherapy drugs.
Several types of cancer immunotherapy drugs. molecules, such as Check points inhibitors Pembrolizumab, Nivolumab anti-cancer antibodies, supercharged immune cells, Cellular products, vaccines that "teach" to attack tumors. Unfortunately, these include mimics of natural immune-system, they don't yet work in everyone.
Immune-based cell therapy: The potential of Immunotherapy combining with Immune-based Cell Therapy and cellular products can be a better way to effectively treat cancer. Autologous Immune cells, NK cells are taken by apheresis from cancer patients before chemotherapies. These Either Cytotoxic T- cells or NK cells are cultured ex vivo after purge with tumor lysate or modified by bioengineering process, after expansion they are reinfused back to patient body to target the cancer cells and completely killed them. Modified T-cells or Chimeric Antigen Receptor expressing T cells CAR-T cells are now approved by FDA in USA for complete cure for a number of lymphoma and Cancer.
Benefits and impact of precision oncology: The Importance of detecting cancer early: The goal of screening exams is to find out cancer before they start to cause symptoms like a lump that cannot be felt and still confined to the organ of origin. Early detection tests and annual health check up with regular cancer screening and molecular profiling could save thousands of lives each year, and more lives could be saved if even more people and their health care providers take advantage of these tests and applied in offering modern treatment.
Present scenario of cancer treatment in Bangladesh: Because of social stigma, lacking of awareness and screening program for early detection, late presentation, inaccessible diagnosis and inadequate nonspecific treatment offered without confirmation of type of cancer are responsible for high mortality in Bangladesh. Though incredible success has achieved in particular branch of healthcare and significantly lowered the maternal and child health mortality by producing world class medicine Bangladesh. unfortunately, about the complex diseases like cancer, medical diagnosis and management are insufficient without advanced knowledge to cope with the challenges. The catastrophic outstanding healthcare expenditure for cancer treatment in Bangladesh is more than $ 4 billion US dollar per year. Random uses of nonspecific chemotherapies make the treatment extremely expensive without any effect. Simultaneously overuse of radiotherapies leading to a high recurrence rate due to development of chemo radio resistance that led to a high morbidity and mortality. As a result, people have lost confidence in medical profession, become desperate to go abroad at huge cost. In this scenario, we have established BioMed Molecular diagnostic facilities to detect cancer early, proper molecular profiling of each cancer patients, confirmation of correct diagnosis with application of biotechnology and Salima Institute for cancer Immunotherapy and Cell Therapy for coordinating cancer management with advanced treatment like targeted therapies, Immunotherapies and Immune based cell therapy.
Precision oncology at BioMed & SIFCIACT: Annual Health Checkup and Early detection at BioMed & Precise treatment at SIFCIACT: Both BioMed and SIFCIACT have been set up to introduce Precision Oncology in Bangladesh in 2020. Now clinicians have the tools to do molecular profiling of each cancer and offer personalized effective treatment. Because of better diagnostic tests, patients are receiving more effective treatment with the hope of completely controlled cancer and living longer with an improved quality of life. At SIFCRACT we have started offering an integrated approach with Targeted Therapy and Immunotherapy after confirmation of molecular profiling & receptor status by PCR Based Mutation Analysis and Immunostaining of molecular Biomarker and PDL 1 immunostaining, with BRAC1 & BRAC2 mutation at BioMed Diagnostics, Molecular Lab. We have treated Breast Cancer, Lung Cancer, Endometrial Cancer patients according to their unique genomic and molecular profiling of cancer, creating unique stories of controlling cancer with better quality of life. A unique story of Kumkum, 36 years patient of Triple Negative Breast Cancer developed brain metastasis after traditional chemo and radiotherapy, we analyse her TNBC and found BRAC1 & 2 mutation and offered her Olaparib monotherapy that metrically controlled her brain metastases and improve survival with better quality of life. Similarly in a patient named Faysal of 39-year-old, Stage 4 NSC Lung cancer, after DNA mutation Analysis, ALK mutation was detected and PDL-1 positive IMS. We offered monotherapy with ALK targeted drug and Pembrolizumab immunotherapy, his cancer is successfully controlled. Combined Targeted and Immunotherapy have been shown to prevent recurrence, secondary metastasis able to keep patient's quality of life (QoL). We have started Clinical and Basic Research projects, based on DNA mutation patterns, and envision progress to drug development for Breast Cancer and other Cancer by 2030.
SIFCIACT will introduce Immune based Cell therapy, CAR-T cells therapy or cellular products by using automated cell culture and expansion technologies to get the most effective outcome for cancer patients in Bangladesh. Today, by sharing and disseminating the unique stories in World Cancer Day, where the needs of people and communities come first, all should come together to advance the future of cancer care in Bangladesh.

Prof Dr Tasnim Ara, MBBS, MS PhD, FACS is CEO of Salima Institute for Cancer Immunotherapy and Cell Therapy (SIFCIACT), BioMed Diagnostics, General and Molecular Lab.
ara.tasnim@gmail.com