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Simple Summary: Often enough, revelation of an aberrant developmental process coincides with manifestation of the malignant process. This is the essence of oncology recapturing ontogeny. This is the epiphany of tumorigenesis recapitulating embryogenesis. When embryonic processes resurface and resurge in an adult person, something is amiss. It is a telltale sign and an unmistakable hallmark of cancer. In many instances, it is a clue to the malignant tumors' stem-cell origins. When a developmental milestone is being improperly and inopportunely expressed in a fully grown individual, something is awry. This pivotal observation is fundamental to the idea that cancer is a stem-cell disease. It is key to unlocking the stem-cell and a unified theory of cancers. From this perspective, we wonder about the clinical implications of oncology recapturing ontogeny in the contexts of neoantigens, tumor biomarkers, and cancer targets. We ponder about the biological ramifications of finding remnants of mini-organs and residuals of tiny embryos in some tumors. We reminisce about classical experiments showing that the embryonic microenvironment possesses antitumorigenic properties. Ironically, a stem-ness niche—in the wrong place at the wrong time—is also an onco-niche. We marvel at the paradox of TGF-beta both as a tumor suppressor and a tumor promoter. We query about the dualism of EMT as a stem-ness trait engaged in both normal development and abnormal disease states, including various cancers. It is uncanny that during fetal development, proto-oncogenes wax, while tumor-suppressor genes wane. Similarly, during cancer development, proto-oncogenes awaken, while tumor-suppressor genes slumber. Importantly, targeting stem-like pathways has therapeutic implications because stem-ness may be the true driver, if not engine, of the malignant process. Furthermore, anti-stem-like activity elicits anti-cancer effects for a variety of cancers because stem-ness features may be a universal property of cancer. When a fetus survives and thrives despite immune surveillance and all the restraints of nature and the constraints of its niche, it is a perfect baby. Similarly, when a neoplasm survives and thrives in an otherwise healthy and immune-competent host, is it a perfect tumor? Therefore, a pertinent narrative of cancer depends on a proper perspective of cancer. If malignant cells are derived from stem cells, and both cells are intrinsically RB1 negative and TP53 null, do the absence of RB1 and loss of TP53 really matter in this whole narrative and an entirely different perspective of cancer? [ABSTRACT FROM AUTHOR]

Poly(ADP-ribose) polymerase (PARP) inhibitors represent one of the successful novel approaches to targeted cancer treatment. Indeed, the US Food and Drug Administration (FDA) has recently approved PARP inhibitors for the treatment of breast and ovarian cancers. Despite the proven efficacy of these agents, certain challenges remain with their use. Among the most important are primary and secondary resistance. Here, we review the mechanism of action of PARP inhibitors and their ability to exploit certain inherent deficiencies among malignant cells to improve cell killing, with a focus on deficiencies in homologous recombination among cells with BRCA1 and BRCA2 mutations. Moreover, we discuss the different mechanisms of resistance including development of secondary resistance and strategies to overcome them. Finally, we discuss the limitations of novel therapeutic interventions and possible future studies to exploit biochemical pathways in order to improve therapeutic efficacy of PARP inhibitors. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course. Background: Cancer is the second leading cause of death internationally, resulting in millions of deaths each year. While treatment in the past has heavily relied on surgery and radiotherapy, chemotherapy and immunotherapy are being increasingly utilized depending on disease presentation. Case Report: A 56-year-old male presented to the Emergency Department with a 3-week history of a rapidly enlarging left supraclavicular neck mass. Computed tomography scan revealed a 12×13 cm mass extending from the angle of the mandible to the supraclavicular area. A biopsy confirmed advanced stage squamous cell carcinoma of the head and neck. The patient was started on a chemotherapy regimen of docetaxel, cisplatin, and 5-fluorouracil (TCF). The tumor progressed through chemotherapy, which was switched to cetuximab; however, this therapy was discontinued after an anaphylactic reaction. Palliative radiation treatment was begun along with pembrolizumab. Pembrolizumab was continued, and after 9 cycles, the patient's cancer was almost in complete remission. Three months later, disease progression was once again noted with pembrolizumab treatment, which was subsequently discontinued. The patient was started on paclitaxel and carboplatin chemotherapy regimen as a last resort, despite failure of prior TCF treatment, and the patient responded, this time with complete remission in 4 months. Conclusions: This case demonstrates a unique outcome in which a patient who previously was resistant to chemotherapy, later responded to chemotherapy after a trial of radiation therapy and immunotherapy. Immunotherapy may have a synergistic effect with radiation therapy and play a role in tumor sensitivity to chemotherapy in head and neck cancer treatment. [ABSTRACT FROM AUTHOR]