Cancer Science & Therapy

The spread of cancer in high intensity is a major cause of concern globally. It is developing in an alarming rate irrespective of age, sex, racial/ethnic group, geographic location and tissue invaded. It is marked by uncontrolled division of cells with the ability to invade other tissues, either by direct growth into the adjacent tissue through invasion, or by the migration into the distant sites by metastasis. According to the latest cancer statistics, there were 14.1 million new cancer related deaths which is expected to rise by 70% over the next two decades with nearly 22 million cases. The rate of cancer related incidence is almost 25% higher in men than in women

Matrix metalloproteinases (MMPs), the entities responsible for eradicating the structure of extracellular matrix - ECM, are the zinc or calcium ion-dependent enzymes. This family of enzymes embodies a vast spectrum of proteases ranging from collagenases, stromelysins to the membrane type MMPs. The tasks linked with these enzymes are significant not only for a sound and stable development of the body but are also found guilty of carrying out angiogenesis, promoting tumor development and thus providing means to disseminate the cancer cells to the sites other than the primary tumor locale. At each step of angiogenesis, MMPs are operating, thereby featuring endothelial cells and several growth factors like VEGF, FGF, etc. Activation of pro-MMP2 with the involvement of MT1-MMP is one of the key steps that lead to the synthesis of blood vessels from an already existing one. For limiting the action of MMPs, various therapeutic techniques highlighting the mechanism of MMP inhibition have been studied. Several agents have been investigated for phase I, II and III clinical trials in combination with other anti-cancer therapies. Natural endogenous inhibitors of MMPs, TIMPs have a limited half-life and are thus not suitable for the desired outcome. Synthetic agents like Marimastat and BMS-275291 have shown reliable results. Nonetheless, explicit research is required for novel agents being designed and synthesized to attenuate the activity of matrix metalloproteinases that are accountable for cancer metastasis.

N-myc downstream regulated gene (NDRG) is, a ubiquitously expressed, a family of cytosolic proteins consists of four members, NDRG1-4. It plays and important role in cancer such as aberrant expression, tumor suppressive, metastatic suppressive and oncogenic functions. In this review, we comprehensively present the expression as well as the clinical and pathological significance of NDRG in human cancers. NDRG1 one of NDRG family which is a ubiquitously expressed protein localized in different tissues of the body, especially breast. It may act as a central regulator of multiple signaling pathways that modulate tumor progression. NDRG2 is expressed in brain, gastric, pancreatic and prostate cells. NDRG3 is highly expressed in testis, prostate, muscle and ovary. Whereas, NDRG4 is highly expressed in brain, hear and colorectal cells. NDRG is down-regulated and associated with the incidence, progression and prognosis of diverse cancers. It is associated with tumor incidence, progression, and metastasis. NDRG has low expression in cancer patients, whereas, inducement of NDRG activity has metastatic suppression effect and also increased in apoptotic effect through increased p53 activity. Metastasis is the spread of a cancer from one organ or part of the body to another not directly connected with it. NDRG is negatively correlated with tumor progression in multiple neoplasms, being a promising new target for cancer treatment. Hence, a drug that has a capacity to enhance an activity of NDRG has a potential to be considered as anti-metastatic agent.

The cell cycle is the process by which mammalian cells regulate proliferation and has S, M, G2 and G1 phase. Loss of these cell-cycle control and increased resistance to apoptosis (programmed cell death) represent major hallmarks of cancer. Cyclic dependent kinases (CDKs), a family of serine/threonine, can control the cell cycle progression and transcription. Besides, they are also involved in regulating mRNA processing, the differentiation of nerve cells and glucose homeostasis. Therefore, CDKs are multiple function proteins. Cellular proliferation, driven by CDKs and their cyclin partners, is decontrolled in cancer; therefore, cancer is considered as a proliferative disorder and targeting the cell cycle, therefore, seems to be a good strategy for new targeted anticancer agents. CDKs activity is closely associated with specific cyclin co-factors and at least 12 separate genetic loci are known to code for the CDKs. Therefore, cyclins are considered to be the gears that are changed to aid the transition between cycle phases. CDKs are generally classified into two major groups, based on whether they control cell cycle progression which includes CDK1 to CDK6 or regulate gene transcription by RNAPII that includes CDK 7, CDK8, CDK9 and CDK19. Increases in level of CDKs are observed in cancer. Inhibition of CDKs, which are the key regulators of the cell-cycle progression and RNA transcription, represents a good strategy for cancer drug discovery and development as well as therapy. This review was briefly described the above-mentioned possible roles of CDKs in the physiological and pathological mechanisms of cancer, further discussing recent advances and challenges in CDKs as a therapeutic target.

Emphasis upon early detection of malignant cellular growths rather than imaging could allow earlier intervention. Photon emissions from malignant cells even when they constitute a very small proportion of the normal organ has been shown to require a technical understanding of the spectral power density profiles that can be predicted by Cosic’s Molecular Resonance Recognition equation. Here we demonstrate experimentally a simpler more robust detection method involving specific filters of photon emissions from cells in culture. Photons from human pancreatic malignant cancer cells displayed conspicuously suppressed spikes of photons within a narrow band (500 nm) but not at 370 nm, 420 nm, 620 nm, 790 nm, or 950 nm increments compared to non-malignant human embryonic kidney cells. Given the recent demonstration that malignant cells can “store” photons within a specific wavelength when pulsed at the same pattern as a yoked magnetic field and re-emit the photons in this wavelength tens of minutes later, diminishment of power within specific 10 nm increments of visible wavelength spectra may serve as an early detection of imminent malignancy.