Targeted therapies that include small molecule inhibitors and monoclonal antibodies have considerably altered the cancer treatment over the past several years. These drugs are currently a part of therapy for several widespread malignancies, including colorectal, breast, pancreatic, and lung cancers, as well as leukemia, multiple myeloma, and lymphoma. The action mechanisms, as well as toxicities of targeted therapies, are different from the action mechanisms of traditional cytotoxic chemotherapy. Targeted therapies are usually better endured than traditional chemotherapy, although they are linked to a number of unfavorable effects, like cardiac dysfunction, acneiform rash, proteinuria, thrombosis, and hypertension. Small molecule inhibitors are acted upon by cytochrome P450 enzymes and are a matter of interactions of multiple drugs. Targeted therapy has elicited new questions concerning the tailoring of treatment of cancer to a tumor of an individual patient, the evaluation of drug toxicity and effectiveness, as well as the cancer care economics. As many people are diagnosed with cancer and as they live longer, main care physicians got to progressively offer care for patients who have obtained targeted therapy for cancer (David).
For many years, the earmark of medical cancer treatment has been endovenous cytotoxic chemotherapy. These drugs aim at cells that are dividing fast, including cancer cells, as well as some normal tissues. As a consequence, several patients go through the classic toxicities of alopecia, myelosuppression, and gastrointestinal signs. In the past several years, though, a spectacular change in therapy for cancer has taken place. Among the new drugs for cancer that have been sanctioned by the Food and Drug Administration in U.S. since the year 2000, 15 have been targeted therapies, in comparison with just five traditional chemotherapeutic agents.
There are two major types of targeted therapy including small molecule inhibitors and monoclonal antibodies (David).
The treatment of cancer based on monoclonal antibody has been set up as among the most victorious strategies of therapy for solid tumors as well as hematologic malignancies in the past two decades. The first compounding of serological methods for discovery of cancer cell surface antigen with hybridoma technology resulted in a sequence of landmark clinical attempts that made way for a new generation antibodies, as well as consequent clinical achievement. Anti-tumor immune responses optimization via Fc alterations also created a key contribution to clinical effectiveness. The immune system interplay modulation with tumor cells via aiming at T cell receptors has come out as a strong new therapeutic plan for tumor therapy and to improve efficacy of cancer vaccine (Andrew, James and Jedd).
A single way that the immune system usually attacks foreign materials in the body is through producing big numbers of diverse antibodies. An antibody, a protein, aims at an exact antigen. Antibodies flow in the body until they get and adhere to the antigen. Once joined, they enroll other immune system parts to damage the cells comprising the antigen.
Several specific antibody copies may be created in the laboratory. These are referred to as monoclonal antibodies, moAbs or mAbs. These antibodies may be helpful in combating diseases since they can be contrived specially to aim at just a particular antigen, for instance one that is present on cancer cells. Monoclonal antibodies are currently employed in the treatment of several diseases, including some cancer types. A key benefit of these drugs is that since they are very specific, they might have just mild fallouts, contrary to a number of other treatments for cancer. But research scientists first need to key out the right antigen to be attacked. For cancer, this is not constantly simple, and thus far mAbs have demonstrated to be more helpful against a number of cancers than others. Throughout the past 20 years, the Food and Drug Administration of US has sanctioned approximately a dozen mAbs for treatment of some cancers. As investigators have discovered more antigens that are connected to cancer, they have managed to produce monoclonal antibodies against more cancers. Clinical investigations of newer mAbs are currently being carried out on several cancer types (American Cancer Society).
The p53tumor suppressor performs a key role in the regulation of apoptosis, cell cycle, senescence, as well as repair of DNA. The protein p53 was discovered in 1979, and later the gene for p53 was described as being responsible for the majority of instances of Li-Fraumeni cancer syndrome, a rare transmissible condition that results in the frequent incidence of many types of cancer in families that are affected (8–10). In fact, because its powerful tumor suppressor function, p53 is among the most often mutated proteins in tumors of humans. Indeed, about 50% of cancers in humans have changes in the p53gene, leading to loss or inactivation of p53 protein (Sanjeev and Shaomeng).
Even in cancers keeping wild-type p53, the role of p53 is efficiently suppressed. The suppression of p53 role is mainly carried out by the murine double minute 2(MDM2) in humans. MDM2 is an oncoprotein, found out by its over manifestation in an impulsively transmuted cell line of mouse cancer. MDM2 has p53-dependent as well as p53-independent roles. MDM2 directly sticks to and makes a complex with p53, suppressing transactivation of p53. A significant amount of data has affirmed that MDM2 is the fundamental node in the pathway of p53 (Sanjeev and Shaomeng).
Aiming at the MDM2-p53 interaction of protein to protein by use of small molecules to reactivate p53 role stands for a potentially attractive strategy for therapy for human cancers treatment keeping wild-type p53. Intensive research attempts in the past years have generated MI-219 and Nutlin-3 as powerful and specific inhibitors of the interaction of MDM2-p53 with suitable pharmacological features. Several of these small-molecule inhibitors, for instance Nutlin-3 and MI-219 analogs, have got to advanced early phase clinical trials or preclinical development. Clinical essaying of these new agents may offer the final proof of the value of this therapeutic scheme for the human cancers treatment (Sanjeev and Shaomeng).
Pancreatic cancer has an etiology multifaceted and exhibits a broad range of pathways of cellular escape that permit it to resist different modalities of treatment. Essential signaling molecules, which run survival pathways downstream especially at points where a number of these pathways crosstalk, offer worth targets for the novel anti-cancer drugs’ development. Family member proteins of Bcl-2 are anti-apoptotic molecules, which are known to be over showed in the majority of cancers including pancreatic cancers. The anti-apoptotic machinery has been associated with the discovered resistance developed to radiation and chemotherapy and, thus, is crucial from the targeted development of drug point of view (Ashiq, Asfar and Ramzi).
For instance, Gossypol is a natural substance that was drawn out from cotton seed in the year 1915. Nevertheless, it was widely studied as birth control device and anti-cancer drug since the 1980s. It is chemically reactive because of its six groups of phenolic hydroxyl as well as two aldehydic groups. Natural gossypol exists in racemic form and levo isoform is presently in clinical assays (Kang and Reynolds). Gossypol was initially utilized in glial tumors’ study, but its action mechanism was not known at that time. The levoisoform has been demonstrated to be more powerful than either isoforms in its growth-repressive effects (Ashiq, Asfar and Ramzi).
Combinations of targeted monoclonal antibodies, as well as small-molecule inhibitor, ought to be further studied so that the beneficial features of both classes of agent may be used to make the most of their effectiveness.
Works Cited
American Cancer Society. Monoclonal antibodies. 2013 . <www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/immunotherapy/immunotherapy-monoclonal-antibodies>.
Andrew, M. Scott, P. Allison James and D. Wolchok Jedd. "Monoclonal antibodies in cancer therapy." Cancer Immunity 12 (2012): 14.
Ashiq, Masood, S. Azmi Asfar and M. Mohammad Ramzi. "Small Molecule Inhibitors of Bcl-2 Family Proteins for Pancreatic Cancer Therapy." Cancers 3 (2011): 1527-1549.
David, E.Gerber. "Targeted Therapies: A New Generation of Cancer Treatments." 2008. 4 June 2013. <http://www.ncbi.nlm.nih.gov/pubmed/18297955>.
Kang, M. H. and C. P. Reynolds. "Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy." Clin. Cancer Res 15 (2009): 1126-1132.
Sanjeev, Shangary and Wang Shaomeng. "Small-Molecule Inhibitors of the MDM2-p53 Protein-Protein Interaction to Reactivate p53 Function: A Novel Approach for Cancer Therapy." Annu Rev Pharmacol Toxicol 49 (2009): 223–241.
