They can be either benign growths or malignant growths. The malignant growths can either have primary or secondary causes. Adenomatous polyps are considered precursors to cancer and cancer becomes invasive once malignant cells cross the muscularis mucosa and invade the cells below. Any cellular changes seen above the lamina propria are considered non-invasive and are labeled atypia or dysplasia. Any invasive carcinoma that has penetrated the muscularis mocos has the potential for lymph node metastasis and local recurrence which will require more aggressive and extensive resection. The Haggitts criteria is used for classification of polyps containing cancer and is based on the depth of penetration. The Haggitts criteria has level 0 through level 4, with all invasive carcinoma of sessile polyp variant by definition being classified as level 4. Level 0: Cancer does not penetrate through the muscularis mucosa. Level 1: Cancer penetrates through the muscularis mucosa and invades the submucosa below but is limited to the head of the polyp. Level 2: Cancer invades through with involvement of the neck of polyp. Level 3: Cancer invades through with involvement of any parts of the stalk. Level 4: Cancer invades through the submucosa below the stalk of the polyp but above the muscularis propria of the bowel wall. Adenomas
Neoplastic polyps of the bowel are often benign hence called adenomas. An adenoma is a tumor of glandular tissue, that has not (yet) gained the properties of cancer.The common adenomas of the colon (colorectal adenoma) are the tubular, tubulovillous, villous, and sessile serrated (SSA).
Lurbinectedin inhibits transcription through a very precise mechanism. Firstly, lurbinectedin binds to specific DNA sequences. It is at these precise spots that slides down the DNA to produce RNA polymerase II that is blocked and degraded by lurbinectedin. Lurbinectedin also has important role in tumor microenvironment. The tumor cells act upon macrophages to avoid them from behaving like an activator of the immune system. Macrophages can contribute to tumor growth and progression by promoting tumor cell proliferation and invasion, fostering tumor angiogenesis and suppressing antitumor immune cells. Attracted to oxygen-starved (hypoxic) and necrotic tumor cells they promote chronic inflammation. So, not only that macrophages inhibit immune system avoiding the destruction of tumor cells, but they also create tumor tissue that allows tumor growth. However, macrophages associated with tumors are cells that are addicted to the transcription process. Lurbinectedin acts specifically on the macrophages associated with tumors in two ways: firstly, by inhibiting the transcription of macrophages that leads to cell death and secondly, inhibiting the production of tumor growth factors. In this way, lurbinectedin normalizes the tumor microenvironment. History
Lurbinectedin was approved for medical use in the United States in June 2020.Efficacy was demonstrated in the PM1183-B-005-14 trial (Study B-005; NCT02454972), a multicenter open-label, multi-cohort study enrolling 105 participants with metastatic SCLC who had disease progression on or after platinum-based chemotherapy. Participants received lurbinectedin 3.2 mg/m2 by intravenous infusion every 21 days until disease progression or unacceptable toxicity.