Targeted Therapy for Cancer

Targeted Therapy for Cancer: Introduction

For cancer treatment, the initial method of chemotherapeutic agents has been cytotoxic drugs. Their action of mitotic inhibition is not limited to cancer cells, particularly profound effects being seen on the haematopoietic system, often with resulting neutropenia or pancytopenia. Targeted therapy conversely seeks to selectively affect cancer cells based on specific molecular characteristics. Targets for therapy are diverse but involve cellular growth, proliferation and, more recently, immune evasion. What is targeted therapy for cancer? Targeted therapy is a newer type of cancer treatment that uses drugs or other substances to more precisely identify and attack cancer cells, usually while doing little damage to normal cells.It has been validated to be a curative treatment for cancer, with many clinical trials and approved by FDA.

A wide variety of targeted therapies are available for the treatment of kidney cancer. The identified targeted therapies work by disrupting specific signalling pathways involved in tumour progression, such as those responsible for angiogenesis and cell proliferation. Tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors are now established classes of drugs used in the treatment of kidney cancer, with a many of them having received regulatory approval to date. such as sorafenib, sunitinib, pazopanib, axitinib, temsirolimus, and everolimus.

In May 2007, sorafenib was approved for “unresectable hepatocellular carcinoma (HCC), and was the first molecular targeted agent for use in liver cancer. Now many new agents are being developed and the combination therapy with sorafenib and standard treatment are being tried to conquer the liver cancer. The new agents includ mTOR inhibitors, Brivanib, Axitinib, E7080, CS1008 and many other agents.

Colorectal cancer (CRC) is one of the most common cancers and the second leading cause of cancer worldwide. Approximately
25% of newly diagnosed patients have already developed metastases,and 50%of all colorectal cancer patients will develop metastases over time as the disease progresses. Systemic therapy was restricted to fluoropyrimidine (5-FU)-based regimens alone or in combination with oxaliplatin or irinotecan for many years
Survival of patients with metastatic colorectal cancer (mCRC) has been significantly improved with the introduction of the monoclonal antibodies targeting the vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR). Novel molecular-targeted agents such as aflibercept and regorafenib have recently been approved.

The increased understanding of the molecular and genetic changes associated with tumorigenesis has led to the development of agents that specifically target these alterations. Targets have included KRAS and downstream factors, such as mitogen-activated protein kinase, epidermal growth factor receptor, vascular endothelial growth factor A, and type I receptor for insulin-like growth factor.

Prostate cancer remains the most commonly diagnosed malignancy and the second leading cause of cancer-related deaths in men in the United States. The current standard of care consists of prostatectomy and radiation therapy, which may often be supplemented with hormonal therapies. Recurrence is common, and many develop metastatic prostate cancer for which chemotherapy is only moderately effective. It is clear that novel therapies are needed for the treatment of the malignant forms of prostate cancer that recur after initial therapies, such as hormone refractory (HRPC) or castration resistant prostate cancer (CRPC). With advances in understanding of the molecular mechanisms of cancer, we have witnessed unprecedented progress in developing new forms of targeted therapy.

Ovarian cancer is the most common cause of mortality of tumors fromgynecologic origin and is often diagnosed after patients have already progressed to advanced disease stage. The current standard of care for treatment of ovarian cancer includes cytoreductive surgery followed by adjuvant chemotherapy. Unfortunately,many patients will recur and ultimately die from their disease. Targeted therapies have been evaluated in ovarian cancer as a method to overcome resistant disease.

Molecular targeted therapies have shown promise in the management of various malignancies, including melanoma, with lower toxicity profiles and better overall survival as compared with conventional therapy. The discovery of BRAF mutations in melanoma led to the development of BRAF inhibitors for the targeted therapy of advanced melanoma. However, growing concerns over drug resistance to molecular targeted therapies including BRAF inhibitors, have spurred efforts to elucidate additional molecular targets for the treatment of advanced melanoma.