Gleevec: a Crushing Blow to Cancer

We have decided to research techniques to better engineer medicines. Making medicine more personalized and tailoring them to a patient’s body chemistry can greatly reduce the risk of side effects and can make treatment more efficient. This can be done by using information about the patient’s genetic makeup and where the disease is localized in order to target the infected cells specifically. We have decided to narrow down our research on cancer, specifically leukemia. Cancer can result from any number of genetic mutations and these malfunctions can lead to an unmanageable division of abnormal cells that then leads to the growth and spread of tumors. Leukemia is a type of cancer originating in the bone marrow. Because leukemias are cancers of the blood, it does not create any solid tumors. Instead, the cancerous leukemia cells circulate in the blood, going virtually everywhere. Diagnosis is commonly made by blood tests or bone marrow biopsy. However, it is difficult to detect leukemia early on since patients with slow-growing types of leukemia don’t present with symptoms until much later, making treatment difficult and less effective. Furthermore, the treatments currently being used, for example stem cells transplants, have a number of side effects such as infertility, chronic fatigue, thyroid dysfunction and the probable risk of developing a second cancer. The challenge, therefore, is to modify the means for early detection of cancer, improving personalized

This drug works by damaging the DNA in cancer cells and stopping them from multiplying. It binds together the strands of DNA so that cells can’t grow and divide (Cancer Research UK, 2015).

Some of traditional drugs may be effective in patients whose cancers have a specific molecular target, and not for other patients. To solve this problem of patient-specificity, pharmaceutical research have seen the expansion of individually tailored cancer treatment, which is an application of targeted therapy, and this is where biopharmaceuticals are. As an increasing part of the population is diagnosed with cancer and as these patients live longer, increasing care will be given to patients who have received these drugs. Moreover, in the case of cancer therapy, those drugs and especially with mABs are a promise of less side effects : recombinant DNA technology makes it possible to genetically engineer an antibody to reduce the risk of host immune response.

"Going off that research, we thought this would be something to move ahead with," says Jeffrey Tibbetts, the lab's medical officer, "There are a fair amount of papers talking about having it injected in models like rats, and it's been used intravenously since the '60s as a treatment for different cancers. After doing the research, you have to take the next step."

Cure – The desired outcome for all patients, but one that is not always achievable.

Every year millions of people are being freshly diagnosed with cancer and a healthy amount is diagnosed with some form of myeloid leukaemia. Few decades ago treatment options for myeloid leukaemia were not so diverse and mortality rate amongst patients were very high. Things have changed dramatically due to the introduction of various treatment options; patients are being able to lead a healthy life prior to their medication period. Though conventional chemotherapy is still used but there are a variety of drugs that have been introduced which could replace chemotherapy and stem cell transplantation in near future as these new generation of drugs have a very specific mode of action and they have a minimal side effect. For example Tyrosine Kinase

After reviewing the study of the effects of chimeric antigen receptor-modified T cells (CAR T-cells) on acute lymphocytic leukemia, it appears that this type of treatment shows promise for the treatment of this and many other difficult-to-kill cancers. This technique was pioneered and developed by Dr. Carl June. He began his research on T cells in the late 1980s to early 1990s while in the Navy. The research he would do and the other researchers he would meet at this time would pave the way for what could be considered to be groundbreaking cancer research today. What started as the study of T cells and their relationship with the HIV virus specifically, would turn into the

In an exclusive interview posted on Inspirery, Dr. Clay Siegall, the CEO of Seattle Genetics, explains why he has focused on targeted therapies for cancer. Siegall, who holds a Ph.D in genetics from George Washington University, co-founded the biotech company to update cancer treatments so that chemotherapy is not so traumatic for cancer patients. Since Seattle Genetics's first ADC, which targets cancer cells as opposed to both cancer and healthy cells, became FDA-approved, Siegall has generated substantial revenue for company by arranging licensing agreements. They took a risk, said Siegall, since only one out of every ten drugs submitted to the FDA receives their approval. Under Siegall's leadership, Seattle Genetics is developing a diverse

Another example is Gleevec from Novartis Oncology this drug went on to have non-orphan indications; it had sales of $2.4 billion in 2010. The brand name of the drug is Gleevec and the generic name is Imatinib. This drug interferes with the growth of some cancer cells. Gleevec is used to treat certain types of leukemia (blood cancer), bone marrow disorders, and skin cancer, or certain tumors of the stomach and digestive system. The most common side effects include Acid or sour stomach, belching, difficulty having a bowel movement (stool), difficulty with moving, discouragement,excess air or gas in the stomach or intestines, fear or nervousness, feeling sad or empty, feeling unusually cold, full or bloated feeling, increased bowel movements, irritability, lack or loss of strength, loose stools, loss of interest or pleasure, muscle stiffness, night sweats, passing gas,

With a change in focus, recent advances in this field have led researchers to develop targeted anticancer agents that have the potential to reduce the side effects associated with classical chemotherapeutics, which include nephrotoxicity, neurotoxicity, leukopenia, thrombocytopenia, nausea, vomiting, and hair loss.5,6 A promising advancement in chemotherapeutics is the development of therapy that targets various biomolecules that are associated with cancer. Known as targeted therapy, this offers significant potential for increasing selectivity by synthesizing compounds that are directed towards cell signaling pathways known as important for cancer cell immortalization.7 Moreover, targeted therapy shows promise with synthesized drugs directed for cancer biomarkers because it will increase selectivity to damage cancer cells instead of healthy cells.8 The early generations of chemotherapeutics largely focused on creating more potent metal complexes, analogous to the structure and function of cisplatin.4 However, with targeted therapy as a promising advancement, the next generation of chemotherapeutics instead focuses on selectivity in the preparation of transition metal complexes that are directed toward specific biomolecules that are known to advance cancer cell

Cancer, by virtue of its knack to transform continuously, has become one of the biggest challenges of the modern oncology. Therefore by doing so, cancerous cells develop resistance to the most of the common treatments viz chemotherapy and radiotherapy (Hanahan and Weinberg, 2011). Although initial treatments may be efficacious in restriction of the disease, but then during the course of time remaining cancer cells acclimatize and develop resistance to the treatments (Liang et al., 2010). Advanced treatment modalities for cancers over the last 20 years encompassing surgery, radiotherapy, chemotherapy, and immunotherapy are not fully satisfactory as the five-year survival rate is continuously decreasing (Siegel et al., 2015). Regardless of

Each drug then had to pass the following three phases of clinical trials under the U.S. Food and Drug Administration:

Imatinib mesylate is a protein tyrosine kinase (RTK) inhibitor that exhibits high specificity and potency for ABL, c-kit, and PDGF receptors, which often harbor activating mutations and are typically mutually exclusive of each other and within specific cancer types.2 The compound has been approved as a targeted chemotherapy for Philadelphia chromosome positive chronic and acute myeloid leukemia (Ph+ CML and AML), Ph+ acute lymphoblastic leukemia (ALL), platelet-derived growth factor receptor (PDGFR) aberrancy-related myelodysplastic or myeloproliferative pathologies, kit+ expressing advanced gastrointestinal stromal tumors (GIST), and for FIP1L1-PDGFRα gene fusion expressing hypereosinophilic syndrome (HES) or chronic eosinophilic leukemia (CEL).1 Imatinib is available in 100 mg and 400 mg tablets for case-dependent single agent or adjunct therapy1. Therapeutic doses range from 100 mg to 800 mg/day, depending on diagnosis, age, and hepatic function.1 The drug exhibits pH-dependent solubility in aqueous solutions (soluble at pH ≤ 5.5), varying solubility in polar protic solvents, and is immiscible in polar aprotic liquids.1

Upon the successful completion of this project, our pioneering platform will enable the targeted delivery of multiple anti-cancer agents, making almost all combinations of chemotherapies currently in clinical use viable candidates for targeted combination chemotherapy.

I began to learn how intricately cancer interplays with the complexity of the human body, and was eager to learn how basic science research could be translated to clinical applications. My most compelling realization at that time was the urgent need for more effective targeted therapies that could overcome drug resistance and focus cytotoxic effects exclusively on cancer cells. I also became aware of challenges in developing therapeutics within the context of cancer heterogeneity. I also presented our research findings at the 2011 Committee on Institutional Cooperation (CIC) Conference at Ohio State University, the 2011 Purdue Summer Research Opportunities Program (SROP) Conference, and the 2011 Mount Holyoke College Learning from Application (LEAP) Symposium.